@article {pmid42632211,
year = {2026},
author = {Medranda, GAD and Lapo-Talledo, GJ and Acosta, JMZ and Alava, LAR and Rodrigues, ALS and Siteneski, A},
title = {Mental Health Disorders and Dementia in Ecuadorian Older Adults: A Nationwide Cross-Sectional Study.},
journal = {Archives of medical research},
volume = {57},
number = {7},
pages = {103504},
doi = {10.1016/j.arcmed.2026.103504},
pmid = {42632211},
issn = {1873-5487},
abstract = {BACKGROUND: Older adults are vulnerable to mental health disorders, and hospitalization typically indicates severity. This study aimed to identify the most common mental health disorders leading to hospitalization among older adults in Ecuador. The frequency of different types of dementia, including Alzheimer's disease, vascular dementia, and other forms of dementia, as well as non-alcohol-induced delirium, was also analyzed.

METHODS: Nine years of nationwide data were examined, including sociodemographic factors, types of disorders, and lengths of hospital stays for each mental health disorder based on ICD-10 criteria. The Ecuadorian National Institute of Statistics and Censuses provided the dataset for analysis based on hospitalization data.

RESULTS: A logistic regression model was used to calculate adjusted odds ratios (aOR). Between 2015 and 2023, Ecuador recorded 10,949 hospitalizations for mental health disorders among the older adult population. The highest hospitalization rates observed were 10.17 per 100,000 inhabitants for mental and behavioral disorders due to psychoactive substance use, predominantly among males. Depressive disorder rates were 9.35 per 100,000 inhabitants, with higher odds in women (aOR 1.78, 95% CI 1.59-1.99). Adults aged 75-79 and 80+ had higher odds of hospitalization for Alzheimer's disease (aOR 7.64 and 10.81, respectively). Hospitalizations due to mental and behavioral disorders related to psychoactive substance use were typically shorter (less than 2 d), while schizophrenia spectrum and bipolar disorders were associated with longer stays (more than 11 d).

CONCLUSIONS: Our findings reveal critical patterns of hospitalizations among older adults due to substance use and depression, providing data for public health policy and future research in similar settings.},
}

@article {pmid42632212,
year = {2026},
author = {Jiang, L and Yan, J and Liu, C and Dong, X and Shi, R and Ma, Q and Sun, S and Sun, Y},
title = {Rational design of halogen-substituted near-infrared fluorescent probes for butyrylcholinesterase: from drug screening to imaging and therapeutic evaluation in Alzheimer's disease.},
journal = {Biosensors & bioelectronics},
volume = {313},
number = {},
pages = {119140},
doi = {10.1016/j.bios.2026.119140},
pmid = {42632212},
issn = {1873-4235},
abstract = {Monitoring butyrylcholinesterase (BuChE) activity is crucial for tracking Alzheimer's disease (AD) progression and evaluating therapeutics; however, high-performance near-infrared (NIR) probes with rapid response and clear design principles remain scarce. Here, we report a series of dicyanoisophorone-based NIR fluorescent probes engineered via a "halogen effect" to systematically tune reactivity toward BuChE. Through spectroscopic screening, the CF3-substituted probe DCNC7 emerged as the optimal candidate, benefiting from the strong electron-withdrawing and hydrophobic nature of the trifluoromethyl group, which enhances binding affinity and catalytic recognition. DCNC7 exhibits over 120-fold NIR fluorescence enhancement upon the BuChE reaction, with fast kinetics (∼15 min), high sensitivity (detection limit 0.0206 U/L), and excellent selectivity. We validated DCNC7 for in situ imaging of BuChE in AD mouse cells and brain tissues, enabling both identification of natural inhibitors and longitudinal assessment of AD progression. Moreover, the screened inhibitor was evaluated for its suppressive effect on BuChE activity in brain tissue and its therapeutic efficacy in vivo. Collectively, DCNC7 offers a reliable tool for AD monitoring, drug screening, and efficacy evaluation, and the halogen effect-based design strategy provides a generalizable route to develop rapid-response, high-affinity enzyme probes for complex disease models.},
}

@article {pmid42632249,
year = {2026},
author = {Afshar, P and Steinberg, KE and O'Hara, LG and Robbins, ED and Banman, DC},
title = {Using Rehabilitation Therapies to Reduce Antipsychotic Use and ED Visits in Individuals With Dementia.},
journal = {Journal of the American Medical Directors Association},
volume = {27},
number = {10},
pages = {106429},
doi = {10.1016/j.jamda.2026.106429},
pmid = {42632249},
issn = {1538-9375},
abstract = {Alzheimer's disease and related dementias represent a significant and growing health care burden in the United States. This article describes the implementation of a rehabilitation-driven, interdisciplinary care model and its impact on antipsychotic medication use and emergency department visits among individuals with dementia in skilled nursing facilities. The approach integrates a research-based dementia staging protocol into occupational, physical, and speech therapies to create individualized care plans that leverage preserved function and the development of customized care strategies. These plans are integrated into facility-wide practices through staff training and ongoing monitoring. Data from 3 affiliated skilled nursing facilities demonstrate significant reductions in antipsychotic use and emergency department visit rates following program implementation. The data suggest that a therapy-forward, person-centered care model can meaningfully reduce the risks associated with pharmacologic interventions and acute hospitalizations, offering an effective strategy for improving dementia care outcomes.},
}

@article {pmid42632354,
year = {2026},
author = {Zhang, L and Wang, S and Gui, Y and Li, D and Li, K and Wang, Y and Xu, Y},
title = {Corrigendum to "TLR2 regulation of NF-κB and NLRP3-driven pyroptosis in Alzheimer's disease" [Neuroscience 598 (2026) 85-99].},
journal = {Neuroscience},
volume = {614},
number = {},
pages = {355},
doi = {10.1016/j.neuroscience.2026.07.052},
pmid = {42632354},
issn = {1873-7544},
}

@article {pmid42632461,
year = {2026},
author = {Sakhvidi, MJZ and Burte, E and Mehrparvar, A and Mortamais, M and Letellier, N and Jacquemin, B},
title = {Ambient air pollution exposure and cognitive aging; mediators and possible pathways: a systematic review on the epidemiological studies.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103330},
doi = {10.1016/j.arr.2026.103330},
pmid = {42632461},
issn = {1872-9649},
abstract = {This systematic review investigates the mediating factors in the relationship between ambient air pollution exposure and cognitive aging. We identified 16 studies examining 72 unique exposure-mediator-outcome associations for six pollutants (PM2.5, PM10, NO2, NOX, black carbon, and PM1 components). The most studied pollutant was PM2.5 (65% of analyses). Cognitive outcomes included memory, cognitive processing speed, and clinically diagnosed conditions such as dementia incidence. Potential mediators spanned mental health outcomes (depression, anxiety, stress), lung function (FEV1, FVC, PEF), vascular diseases (stroke, hypertension), inflammation (CRP), metabolic factors (type 2 diabetes), sleep, and neuroanatomical changes. The quality of mediation analysis reporting was generally good, but most studies had some risk of bias, particularly in outcome assessment and confounding adjustment. Cardio and Cerebro-vascular diseases emerged as a potential key mediator. Mental health outcomes, sleep, and lung function also showed mediating potential, but further research is needed to confirm these findings. This review highlights the need for rigorous causal mediation analyses and standardized reporting to better understand the complex pathways linking air pollution to cognitive aging, in order to identify targeted preventive measures to reduce the negative impact of ambient air pollution on cognitive health.},
}

@article {pmid42632510,
year = {2026},
author = {Yi, F and Ma, J and Zhao, R and Xie, Q and Lu, S and Zhang, K and Zhong, Z and OuYang, H and Qin, Y and Xu, M and Xue, Q and Wang, X and Wei, W and Liu, Y},
title = {Zonisamide improves cognitive impairment and psychiatric symptoms related with SAPAP3 in mouse models of Alzheimer's disease.},
journal = {European journal of pharmacology},
volume = {1033},
number = {},
pages = {179279},
doi = {10.1016/j.ejphar.2026.179279},
pmid = {42632510},
issn = {1879-0712},
abstract = {BACKGROUND: Alzheimer's disease (AD) is characterized by pathological changes in Aβ&Tau, cognitive impairment, and may also manifest psychiatric symptoms. Zonisamide (ZNS) has been demonstrated its improvement of cognitive dysfunction in T2DM mice in our previous study. However, the efficacy and mechanism of ZNS in treating AD remain unclear.

AIM: We aims to investigate the therapeutic efficacy of ZNS for AD and its potential molecular mechanisms.

METHODS: Three-month-old 5xFAD mice were treated with ZNS (20 mg/kg, i.p.) for 12-week. The behavioral test assesses cognitive function and psychiatric symptoms. Aβ-PET/CT, immunofluorescence, and Thioflavine-S staining assessed the levels of Aβ plaques. Proteomics and Western blot analyses evaluated synapse-associated proteins, amyloid precursor protein (APP) related proteins and phosphorylated tau.

RESULTS: We discovered for the first time that ZNS significantly improved spatial learning and memory, and also alleviated psychiatric symptoms in 5xFAD. Besides, ZNS increased PSD95, SYP, BDNF, and SAP90/PSD-95-related protein 3 (SAPAP3), which plays a crucial role in compulsive-like behaviors. Importantly, siRNA-mediated knockdown of SAPAP3 in N2A/APP cells inhibited the regulatory effect of ZNS on PSD95 and NMDAR2A (NR2A). In addition, ZNS treatment reduced Aβ deposition in the brain. It also downregulated APP, p-APP (Thr668), BACE1, and PS1, and attenuated tau phosphorylation at Ser396 by inhibiting its upstream kinase ERK1/2 activity.

CONCLUSION: ZNS exerts neuroprotective effects in 5xFAD mice and improves AD-related cognitive impairment and AD-like lesions, which establishes ZNS as a promising therapeutic avenue for AD and its associated psychiatric symptoms.},
}

@article {pmid42632547,
year = {2026},
author = {Abdelaziz, AM and Eladawy, RM},
title = {Immunopharmacological reprogramming of innate immune memory in Alzheimer's disease: From microglial priming to therapeutic resilience.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {118381},
doi = {10.1016/j.bcp.2026.118381},
pmid = {42632547},
issn = {1873-2968},
abstract = {Alzheimer's disease (AD) is increasingly recognized as a disorder driven by dysregulated innate immunity rather than merely amyloid‑β accumulation. Microglia, the brain's resident innate immune cells, acquire long‑term functional memory, a process known as trained immunity or innate immune memory, through epigenetic and metabolic reprogramming. In AD, chronic exposure to amyloid‑β and tau aggregates locks microglia into a maladaptive primed state characterized by altered histone modifications (H3K4me3, H3K27ac), sustained glycolysis via the HIF‑1α/mTOR axis, and impaired phagocytic function, perpetuating neuroinflammation and neurodegeneration. This review critically synthesizes recent advances that define the molecular architecture of microglial immune memory, including epigenetic rewiring, immunometabolic shifts, and intercellular crosstalk with astrocytes and the gut microbiome. We evaluate the emerging immunopharmacological toolbox designed to reverse maladaptive priming and restore neuroprotective resilience, focusing on small‑molecule NLRP3 inflammasome inhibitors (HT‑6184, DFV890, BGE‑102), TREM2 agonists (VG‑3927, MNA‑001), metabolic modulators (metformin, rapamycin), trained immunity‑based vaccination (BCG), specialized pro‑resolving mediators (maresin 1, resolvin D1, lipoxin A4), and senolytics. Clinical‑stage agents and their mechanisms of action are highlighted. We argue that the next generation of AD therapeutics must move beyond target suppression toward the functional reprogramming of brain innate immunity, and we propose a biomarker-guided, patient-stratified framework that integrates multimodal immunopharmacology, combining NLRP3 inhibition, TREM2 agonism, metabolic reprogramming, and resolution pharmacology to restore immune homeostasis. Harnessing the plasticity of innate immune memory offers a transformative paradigm for disease‑modifying therapy in AD.},
}

@article {pmid42632804,
year = {2026},
author = {Salminen, LE and Wang, X and Petkus, AJ and Fennema-Notestine, C and Elman, JA and Hagler, DJ and Kaufman, JD and Millstein, J and Braskie, MN and Liu, J and Cho, HJ and Kothapalli, D and Thompson, PM and Beavers, DP and Espeland, MA and Gatz, M and Resnick, SM and Frahmand, I and Rapp, SR and Finch, CE and Chen, JC and Kremen, WS and Franz, CE},
title = {Erratum to "Air pollution is linked to divergent cortical thickness patterns in brain regions vulnerable to Alzheimer's disease" [Neurotoxicology 115 (2026) 103495].},
journal = {Neurotoxicology},
volume = {},
number = {},
pages = {103551},
doi = {10.1016/j.neuro.2026.103551},
pmid = {42632804},
issn = {1872-9711},
}

@article {pmid42632811,
year = {2026},
author = {Singh, VB and Sella, RN},
title = {Design and evaluation of a novel peptide-EV complex for targeted Alzheimer's disease therapy.},
journal = {Journal of drug targeting},
volume = {},
number = {},
pages = {1-30},
doi = {10.1080/1061186X.2026.2724027},
pmid = {42632811},
issn = {1029-2330},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder that involves the formation of amyloid-β (Aβ) aggregates, and the development of targeted therapeutic strategies is needed. In the current work, we report the rational design of H102-CP05, a 22-residue chimeric peptide that integrates the β-sheet breaker peptide H102 with the CD63-targeting anchor CP05 to enable extracellular vesicle (EV)-mediated delivery of an Aβ-inhibitory payload. Computational analysis confirmed favorable physicochemical properties and a non-allergenic profile. In silico immunogenicity assessment and C-IMMSIM simulation demonstrated a low risk of anti-drug antibody formation under chronic dosing conditions. Homology modelling and HADDOCK docking (score: -147.2 ± 4.6) predicted a computationally favourable CD63 binding configuration, while 100 ns molecular dynamics simulations confirmed structural stability in both aqueous and EV-mimetic lipid bilayer environments. In vitro cytotoxicity against HEK-293 cells revealed no significant toxicity (10-100 µM). Zebrafish embryo studies indicated acceptable developmental safety at lower concentrations, with concentration-dependent bradycardia observed at higher doses warranting further cardiovascular evaluation. Thioflavin T fluorescence assays demonstrated dose-dependent inhibition of Aβ fibrillation, with near-complete suppression at 100 µM. These findings collectively support H102-CP05 as a promising EV-displayed therapeutic candidate for AD.},
}

@article {pmid42633094,
year = {2026},
author = {Vitali, F and Raikes, AC and Merlini, S and Shang, Y and Torrandell-Haro, G and Hernandez, GD and Yin, F},
title = {Sex- and APOE-specific transcriptomic drug repurposing identifies four candidate therapeutics for Alzheimer's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {3},
pages = {e70303},
pmid = {42633094},
issn = {2352-8737},
abstract = {INTRODUCTION: Alzheimer's disease (AD) risk is strongly modified by biological sex and apolipoprotein E (APOE) genotype, yet these factors are rarely incorporated into drug discovery efforts. We hypothesized that sex- and APOE-specific transcriptomic signatures define distinct molecular endotypes of AD which can be therapeutically targeted through precision drug repurposing using an integrative data framework.

METHODS: We analyzed frontal cortex RNA sequencing data from 369 individuals in the Religious Orders Study Rush Memory and Aging Project cohort (APOE ε3/ε3 and APOE ε3/ε4) to derive sex- and genotype-specific AD gene expression signatures. Differential expression and Gene Ontology enrichment analyses identified biological processes uniquely or differentially perturbed across groups. Drug-induced perturbation signatures from the Library of Integrated Network-Based Cellular Signatures database were queried to identify US Food and Drug Administration-approved compounds predicted to reverse AD-associated signatures. Top candidates were validated using the PearlDiver-Mariner claims database to assess AD risk associations.

RESULTS: Transcriptomic dysregulation varied markedly across groups. Female APOE ε3/ε3 AD brains exhibited the greatest number of differentially expressed genes (n = 8903), whereas male APOE ε3/ε3 showed the fewest (n = 640). APOE ε4 carriers demonstrated enrichment of immune and inflammatory pathways, including cytokine signaling and extracellular signal-regulated kinase cascade activation, whereas APOE ε3/ε3 groups exhibited downregulation of synaptic organization, vesicle trafficking, and bioenergetic processes. Drug reversal analysis identified four candidates: riluzole, chloroquine, acetazolamide, and anagrelide. In population-level validation, riluzole (relative risk [RR] = 0.52; 95% confidence interval [CI]: 0.40-0.68), chloroquine (RR = 0.56; 95% CI: 0.55-0.58), and acetazolamide (RR = 0.76, 95% CI: 0.73-0.79) were associated with significantly reduced AD risk, whereas anagrelide exhibited increased risk. Protective associations for riluzole, chloroquine, and acetazolamide held in both sexes, with stronger effects in women.

DISCUSSION: Sex and APOE genotype define biologically distinct AD transcriptomic states, with subgroup-specific and shared pharmacologic reversibility. Integrating stratified transcriptomics with population-scale validation identified clinically actionable candidates supporting an AD precision drug repurposing framework.},
}

@article {pmid42633124,
year = {2026},
author = {Mehta, RI and Jaisa-Aad, M and Teixeira, CVL and Worhunsky, PD and Malone, JE and Ward, M and Keith, CM and Phelps, HE and Sharif, K and Pockl, S and Rajabalee, N and Marano, GD and Bojarski, L and Smith, S and Massey, KM and Hatfield, M and D'Haese, PF and Rezai, AR and Haut, MW},
title = {Anti-amyloid immunotherapy and brain volume trajectories in early-onset versus late-onset Alzheimer's disease.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70457},
pmid = {42633124},
issn = {2352-8729},
abstract = {INTRODUCTION: Accelerated brain volume loss has been observed following trials of anti-amyloid beta immunotherapy (AAT); however, there is limited understanding of this paradoxical phenomenon in early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD).

METHODS: We retrospectively analyzed brain volume changes over a 1-year period following initiation of AAT. Annualized rates of brain volume alteration were calculated, and linear mixed-effects models were performed to assess brain volume trajectories in EOAD versus LOAD.

RESULTS: One hundred fourteen participants (35 with EOAD; 79 with LOAD; mean baseline MMSE: 27) were analyzed. Ventricular expansion, measuring ∼15%/year, and whole-brain atrophy occurred in both groups. LOAD showed ∼1.7× greater hippocampal atrophy compared with EOAD, independent of baseline cerebral amyloid burden, though global cortical amyloid burden predicted whole-brain and hippocampal atrophy (p < 0.001).

DISCUSSION: Brain atrophy with prominent ventricular expansion occurs in early-stage EOAD and LOAD following AAT. Additional studies are needed to elucidate the mechanisms and implications of this post-immunotherapy effect.},
}

@article {pmid42633139,
year = {2026},
author = {Azargoonjahromi, A and Abutalebian, F and Nasiri, H},
title = {NF-κB across the Alzheimer disease spectrum: Context-dependent protective and pathogenic roles.},
journal = {IBRO neuroscience reports},
volume = {21},
number = {},
pages = {518-541},
pmid = {42633139},
issn = {2667-2421},
abstract = {Nuclear factor kappa B (NF-κB) has been implicated in both protective and detrimental processes in Alzheimer disease (AD), creating an apparent contradiction in the literature. Increasing evidence, however, indicates that these divergent effects reflect differences in cell type, molecular configuration, activation kinetics, disease state, and the surrounding pathological environment rather than a true biological paradox. Under transient and tightly regulated conditions, NF-κB can support neuronal survival, stress adaptation, antioxidant defense, and selected compensatory responses to amyloid-β pathology. In contrast, persistent or disease-conditioned signaling is more consistently associated with amyloidogenic processing, tau propagation, chronic neuroinflammation, impaired proteostasis, neuronal dysfunction, and neurovascular injury. The available evidence therefore supports an asymmetric framework in which protective effects are confined to relatively specific molecular and temporal settings, whereas sustained pathological signaling is supported across a broader range of disease-relevant models and cellular processes. This distinction argues against indiscriminate activation or global inhibition of NF-κB, either of which could disrupt physiological functions while failing to selectively suppress disease-driving pathways. Therapeutic strategies should instead target defined pathological NF-κB programs within the relevant cell type and disease context while preserving adaptive and homeostatic signaling. This review synthesizes the context-dependent roles of NF-κB in AD and provides a framework for reconciling its apparently opposing effects.},
}

@article {pmid42633185,
year = {2026},
author = {Rashidi, Y and Barjasteh, AH and Ilaghi, M and Pozvei, A and Soltanpour, M and Jahangiri, S and Radmanesh, M and Pourbafrani, A and Hosseini Faegh, SH and Bagheri, F and Zarifbargi, S and Pourhanifeh, MH},
title = {Baicalin and CNS-related diseases: new insights into neuroprotective potentials based on underlying mechanisms.},
journal = {Biochemistry and biophysics reports},
volume = {47},
number = {},
pages = {102741},
pmid = {42633185},
issn = {2405-5808},
abstract = {Central nervous system (CNS)-associated diseases such as neurological (including cerebral ischemia-reperfusion injury and stroke, Parkinson's disease, Alzheimer's disease, traumatic brain injury, and spinal cord injury) and psychological (including depression, anxiety, attention deficit hyperactivity disorder, and dementia) diseases are known as serious problems for public health worldwide. These diseases contribute to the occurrence of several disabilities and even death in affected individuals, and also decrease their quality of life. Therefore, discovering effective complementary treatments is essential. Recently, baicalin, a multifunctional natural product, has attracted much attention because of its therapeutic potentials in various diseases. Moreover, it has been shown that this agent can regulate key cellular and molecular processes in human diseases. In the case of CNS-related diseases, this review article aimed to summarize and discuss the available data from in vivo and in vitro investigations on the therapeutic application of baicalin, based on underlying mechanisms.},
}

@article {pmid42633327,
year = {2026},
author = {Alipour, M and Hajipour-Verdom, B and Ashrafi, F and Roodsari, SR and Nohesara, S and Zali, A and Ashrafi, F},
title = {Magnetoreceptive CRY/MagR complexes: linking circadian redox signalling to protein aggregation in Alzheimer's and Parkinson's disease.},
journal = {ADMET & DMPK},
volume = {14},
number = {},
pages = {3366},
pmid = {42633327},
issn = {1848-7718},
abstract = {BACKGROUND AND PURPOSE: Neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) pose an escalating challenge to neuroscience, as disease-modifying therapies remain elusive despite substantial advances in molecular and cellular understanding. These disorders share convergent pathological features, including protein misfolding and aggregation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, and disruption of circadian regulation. Identifying integrative frameworks that connect these processes is therefore essential for advancing conceptual models of neurodegeneration. This review examines magneto-proteins, with a particular focus on CRY/MagR-based magnetoreceptor complexes, as emerging biological systems that may intersect with key molecular pathways implicated in AD and PD.

EXPERIMENTAL APPROACH: We synthesized literature from neuroscience, biophysics, and circadian biology to evaluate the potential relevance of magnetoreceptor mechanisms to AD and PD pathology. We first summarized the core neuropathological mechanisms underlying both diseases, including amyloid-β and tau pathology in AD and α-synuclein aggregation and dopaminergic vulnerability in PD. We then outlined the biophysical foundations of magneto-protein function, emphasizing cryptochrome-mediated radical pair mechanisms, iron-sulphur cluster-dependent magnetic sensitivity, and their established roles in redox signalling and circadian biology.

KEY RESULTS: Accumulating experimental evidence from cellular and animal models suggests that CRY/MagR-associated pathways can modulate oxidative stress, mitochondrial bioenergetics, protein aggregation dynamics, autophagic processes, and circadian control of neuronal metabolism. These processes closely overlap with molecular determinants of neuronal vulnerability in AD and PD. However, direct validation in mammalian and human systems remains limited and controversial, representing a critical knowledge gap.

CONCLUSION: The mechanistic convergence between magnetoreceptor biology and neurodegenerative pathology warrants critical evaluation but remains largely speculative in humans. By integrating findings across disciplines, this review positions CRY/MagR-based magneto-proteins as a conceptual platform for exploring how magnetic field-responsive molecular systems may inform our understanding of neurodegenerative disease mechanisms, while emphasizing the need for rigorous mammalian validation.},
}

@article {pmid42633398,
year = {2027},
author = {Chen, H and Si, Y and Cheng, Q and Yu, Q and Cui, Z and Yu, S and Zhao, X and Jin, Y and Wang, Y and Li, M and Lu, Z},
title = {Therapeutic potential and underlying mechanisms of engineered young plasma-derived exosomes in Alzheimer's disease.},
journal = {Bioactive materials},
volume = {67},
number = {},
pages = {497-523},
pmid = {42633398},
issn = {2452-199X},
abstract = {Exosomes (EXOs) derived from the plasma of young individuals are believed to have the potential to ameliorate aging-related memory deficits. However, their specific roles and mechanisms in Alzheimer's disease (AD) therapy have not yet been systematically investigated. In this study, the rabies virus glycoprotein-targeting peptide (RVG-29) was conjugated to the surface of young plasma-derived EXOs to construct RVG-engineered EXOs (RVG-EXOs), and their therapeutic potential and underlying mechanisms in AD models were systematically evaluated. In 3×Tg AD model mice, exogenous administration of young plasma-derived EXOs and their engineered product (RVG-EXOs) revealed that RVG-EXOs could more efficiently enter brain tissue and target neurons, significantly reduce Aβ plaque and phosphorylated Tau (P-Tau) pathological deposition, restore synaptic structure, promote neuronal survival, and improve cognitive behavior. Mechanistic studies demonstrated that RVG-EXOs inhibited RPTOR expression, thereby activating the autophagy pathway and promoting the clearance of pathological proteins. Both in vitro and in vivo experiments confirmed that overexpression of RPTOR significantly suppressed the therapeutic effects of RVG-EXOs. single-cell transcriptomic profiling further revealed that RVG-EXOs not only increased neuronal proportion and modulated excitatory/inhibitory neuronal balance but also reshaped the microglial landscape by reducing deleterious disease-associated while increasing homeostatic surveillant microglia. In summary, this study not only reveals for the first time the potential value of young plasma-derived EXOs in AD treatment but also, through RVG engineering strategies and the elucidation of the RPTOR-autophagy mechanism, provides new insights for targeted therapy of neurodegenerative diseases.},
}

@article {pmid42633445,
year = {2026},
author = {Alobu, EJ and Uchewa, OO and Ibegbu, AO},
title = {Novel cell markers with altered expression in brain aging and Alzheimer's disease: A review.},
journal = {IBRO neuroscience reports},
volume = {21},
number = {},
pages = {604-613},
pmid = {42633445},
issn = {2667-2421},
abstract = {Aging and Alzheimer's disease are complex processes marked by continuous neuronal loss, disrupted neural networks, and cognitive decline. The past decade has seen advances in genomics, proteomics, and single-cell RNA sequencing, enabling the discovery of cellular markers with distinct gene expression patterns. This review aims to compile recent markers of aging and Alzheimer's disease in immune, glial, and neuronal cells, which are increasingly vital for enhancing diagnostic precision and monitoring disease progression. Markers such as Triggering receptor expressed on myeloid cells 2 (TREM2) and Cluster of differentiation 33 (CD33) facilitate immune responses and function as indicators of neuroinflammation and amyloid-beta clearance; Glial fibrillary acidic protein (GFAP) and aquaporin-4 serve as indicators of gliosis and impaired interstitial fluid drainage; Postsynaptic density protein 95 (PSD-95), Synaptosomal-associated protein 25 (SNAP25), and aberrant tau phosphorylation signify synaptic degradation and cytoskeletal instability characteristic of Alzheimer's pathology. The breakdown of the blood-brain barrier is associated with endothelial nitric oxide synthase (eNOS) and vascular cell adhesion molecule 1 (VCAM-1). The markers were identified using cutting-edge technologies that unveiled variations in gene expression across cell types, brain regions, and disease stages. This cellular heterogeneity improves understanding of Alzheimer's disease (AD) progression and brain aging, clarifies molecular pathways, and may be used for prognostic and diagnostic purposes after thorough validation. Novel cellular markers with altered expression profiles are still being identified through ongoing research, which could be crucial for improving our understanding of and ability to treat neurodegenerative diseases.},
}

@article {pmid42633486,
year = {2026},
author = {Ramić, A and Divjak, T and Hadrović, L and Pavlinić, M and Matošević, A and Bosak, A and Borovec, J and Bakota, B and Hrenar, T and Primožič, I},
title = {Cholinesterases inhibition profiles with Ugi-derived peptidemimetics: A combined experimental and computational study.},
journal = {ADMET & DMPK},
volume = {14},
number = {},
pages = {3292},
pmid = {42633486},
issn = {1848-7718},
abstract = {BACKGROUND AND PURPOSE: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are crucial enzymes implicated in various neurological disorders, including Alzheimer's disease. Developing selective inhibitors for either enzyme is one of the key therapeutic strategies. This study aimed to synthesize and evaluate a novel series of peptidomimetics for their ability to inhibit both human AChE and BChE, with a focus on identifying compounds exhibiting joint inhibitory activity or selectivity for BChE.

EXPERIMENTAL APPROACH: Eleven peptidomimetics were synthesized using the Ugi four-component reaction. In vitro enzyme inhibition assays were performed to determine the dissociation constants (K i) for both human AChE (hAChE) and human BChE (hBChE). Principal component analysis was employed to analyse the inhibition data and map compound selectivity. To investigate the molecular interactions between the peptidomimetics and the BChE active site, quantum-chemical docking simulations were conducted.

KEY RESULTS: All synthesized compounds exhibited reversible, micromolar inhibition of both hAChE and hBChE. Two compounds demonstrated significant BChE selectivity, with 279- and 169-fold higher preference for BChE, respectively. Principal component analysis revealed distinct clusters correlating with preferential binding to either enzyme. Docking simulations supported these findings, highlighting key stabilizing interactions (primarily π-π stacking) between the peptidomimetics and BChE, explaining superior selective and joint inhibitory activity.

CONCLUSION: This work demonstrates the successful synthesis and characterization of novel peptidomimetics with varying degrees of hAChE and hBChE inhibition, including compounds with notable BChE selectivity. The combination of experimental data and computational modelling provides valuable insights into the structural basis of enzyme inhibition and establishes a foundation for rational design of more potent and selective cholinesterase inhibitors based on the designed scaffold.},
}

@article {pmid42633759,
year = {2026},
author = {Huang, Y and Ma, T and Wu, R and Johansson, L and Wang, S and Sun, Y and Ma, B and Yang, J and Zhao, Y and Zhang, N and Lu, Q},
title = {The development of the International Classification of Functioning, Disability and health (ICF) checklist for Alzheimer's disease home-based community care: a multi-method study.},
journal = {Disability and rehabilitation},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/09638288.2026.2715074},
pmid = {42633759},
issn = {1464-5165},
abstract = {PURPOSE: To develop an International Classification of Functioning, Disability and Health (ICF) Checklist tailored to the home-based community care needs of individuals with Alzheimer's Disease (AD), known as the ICF-ADHC, to support person-centred functional assessment and interdisciplinary care planning.

METHOD: A multi-method study was conducted in three phases. First, a literature review identified candidate ICF categories related to AD home-based community care, which were extracted and linked using standardized ICF linking rules. Second, interviews with 22 family caregivers were conducted to explore perceived care needs of individuals with AD, and the qualitative data were similarly linked to ICF categories. Third, a two-round Delphi survey with 14 experts in geriatric care, rehabilitation, and dementia was used to validate and refine the candidate categories. Final selection was based on importance ratings and advisory panel discussions.

RESULTS: The finalized ICF-ADHC includes 43 categories: 13 categories from body functions, 15 from activities and participation, and 15 from environmental factors. These categories capture essential domains for assessing and planning home-based care for individuals with AD.

CONCLUSIONS: The ICF-ADHC provides a comprehensive and standardized checklist for assessing the functional and contextual needs in AD home-based community care. It facilitates comprehensive assessment and supports individualized care planning.},
}

@article {pmid42633943,
year = {2026},
author = {Fujita, S and Fushimi, Y and Otsuka, Y and Murata, K and Buonincontri, G and Koerzdoerfer, G and Nittka, M and Fukunaga, I and Takabayashi, K and Hagiwara, A and Motoi, Y and Nakajima, M and Murakami, K and Shima, A and Kubota, M and Bilgic, B and Kamagata, K and Sawamoto, N and Abe, O and Nakamoto, Y and Aoki, S},
title = {Brain Amyloid Burden Mapping Using MR Fingerprinting Aided by Deep Learning.},
journal = {Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine},
volume = {25},
number = {4},
pages = {},
doi = {10.2463/mrms.mp.2026-0112},
pmid = {42633943},
issn = {1880-2206},
mesh = {Humans ; Positron-Emission Tomography ; *Deep Learning ; *Magnetic Resonance Imaging/methods ; *Brain/diagnostic imaging/metabolism ; Prospective Studies ; *Amyloid beta-Peptides/metabolism ; Reproducibility of Results ; Female ; Male ; *Brain Mapping/methods ; Alzheimer Disease/diagnostic imaging ; },
abstract = {PURPOSE: To develop and externally validate a non-invasive framework for quantifying brain amyloid-β (Aβ) deposition using magnetic resonance fingerprinting (MRF) and neural network-based decoding, with positron emission tomography (PET) as the reference standard.

METHODS: This prospective multi-site study included 44 participants from 2 sites who had undergone, or were scheduled to undergo, Aβ PET within 1 year. MRF was performed on a 3T MR system using a 2D fast imaging with steady-state precession sequence with B1 correction, covering the whole brain in 9.5 min. PET images were co-registered to the MRF space, and regional amyloid load was calculated using an automated template-based pipeline. An inverse mapping function was implemented to convert MRF signals into amyloid burden maps. Repeatability, agreement with PET-based centiloid values, and associations with cognitive scores were evaluated.

RESULTS: The generated amyloid maps were visually similar to PET images. Test-retest analysis showed high repeatability, with a coefficient of variation of 1.8 ± 1.3% and an intraclass correlation coefficient of 0.84. In the external test set, MRF-based measurements correlated significantly with PET centiloid scores (Spearman's ρ = 0.589, P = 0.015) and Montreal Cognitive Assessment scores (ρ = -0.543, P = 0.020).

CONCLUSION: The proposed framework enables non-invasive Aβ mapping using a clinically feasible MRI protocol and may support repeated assessment for monitoring during anti-amyloid treatment.},
}

Humans
Positron-Emission Tomography
*Deep Learning
*Magnetic Resonance Imaging/methods
*Brain/diagnostic imaging/metabolism
Prospective Studies
*Amyloid beta-Peptides/metabolism
Reproducibility of Results
Female
Male
*Brain Mapping/methods
Alzheimer Disease/diagnostic imaging

@article {pmid42633973,
year = {2026},
author = {Lv, X and Shen, K and Zhao, Q and Peng, G and Liu, H and Gao, F and Pan, X and Chen, W and Lu, P and Zhang, H and Zhang, S and Xing, M and Chen, Q and Wang, Y and Cheng, Z and Wang, Y and Zeng, S and Xie, F and Pan, Y and Shen, Y and Chen, X and Shi, J},
title = {Head-to-head comparison of plasma biomarker assays across platforms for amyloid pathology in a multicenter cohort.},
journal = {Science bulletin},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.scib.2026.08.018},
pmid = {42633973},
issn = {2095-9281},
abstract = {BACKGROUND: With the advancement of anti-amyloid treatments for Alzheimer disease, accurate assays for amyloid-β (Aβ) pathology are essential. Plasma phosphorylated tau 217 (p-tau217) is a blood-based biomarker, but its performance varies across platforms, necessitating head-to-head comparisons.

METHODS: This multicenter study evaluated 9 plasma p-tau217 assays (6 including Aβ42 measurements) for detecting amyloid positron emission tomography (PET) positivity. The final analysis included 431 participants from 10 memory clinics in China (median age, 68.0 years; 61.7% women; 64.0% amyloid PET-positive): 30 cognitively unimpaired individuals, 230 with mild cognitive impairment, and 171 with dementia. All plasma samples underwent blinded, batch-matched testing in a central laboratory across chemiluminescence immunoassay (Fujirebio, Beckman, Vazyme, manufacturer A), single-molecule immunoassay (Quanterix, Lychix, iomicsBio, manufacturer B), and multiplex bead-based flow cytometric immunoassay (CellGene).

RESULTS: Seven of the 9 assays showed acceptable performance (area under the curve [AUC] 0.899-0.930), whereas 2 showed lower performance (AUC <0.800; P < 0.001). Under a two-cutoff approach (90% sensitivity/90% specificity), these 7 high-performing assays yielded an intermediate zone of 2.8% to 13.7%. Performance remained robust in mild cognitive impairment and dementia subgroups. Adding Aβ42 showed assay- and population-dependent effects. Manufacturer-recommended and previously published cutoffs showed variable performance in this independent cohort.

CONCLUSIONS: Several plasma p-tau217 assays demonstrated strong diagnostic accuracy for amyloid PET positivity in this cross-sectional memory-clinic cohort, although performance varied across platforms and cutoff transferability was limited. Further longitudinal studies with predefined clinical outcomes are needed to determine prognostic value and clinical utility.},
}

@article {pmid42634158,
year = {2026},
author = {Qian, X and Wang, Z and Cui, P and Chen, S and Xue, Y and Yang, Y and Xu, J and Liu, X and Ding, G and Tang, H},
title = {Multi-omics identification of haptoglobin as a novel target for increased Alzheimer's disease risk associated with obesity through inhibiting the phagocytosis of Aβ by disease-associated microglia.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71759},
doi = {10.1002/alz.71759},
pmid = {42634158},
issn = {1552-5279},
support = {24YF2725800//Shanghai Sailing Program/ ; 2025M772189//China Postdoctoral Science Foundation/ ; 20231207//Shanghai Fengxian District Science and Technology Commission Social Science and Technology Development Fund Project/ ; //The Sixth People's Hospital of Shanghai medical group projects/ ; YJKT-25-02-003//Shanghai Fengxian District Central Hospital Research Project/ ; },
mesh = {*Alzheimer Disease/genetics/metabolism ; *Haptoglobins/metabolism/genetics ; *Microglia/metabolism ; *Obesity/complications/metabolism/genetics ; Humans ; *Amyloid beta-Peptides/metabolism ; *Phagocytosis/physiology ; Animals ; Multiomics ; Body Mass Index ; Female ; Male ; },
abstract = {INTRODUCTION: Obesity may increase Alzheimer's disease (AD) risk, yet the underlying mechanisms remain unclear.

METHODS: We investigated this link through global epidemiology, Mendelian randomization (MR), transcriptomics, clinical cohort validation, and mechanistic exploration.

RESULTS: High body mass index (BMI)-attributable AD disability-adjusted life years and deaths increased 4-fold from 1990-2021, with projections indicating a tripling by 2050. MR analyses found that elevated BMI was genetically related to increased AD risk. Haptoglobin (HP) was identified as a core mediator between them. HP expression was correlated with plasma AD biomarkers and cognitive scores. Mechanistically, HP localized to plaque-associated microglia and suppressed microglial amyloid beta (Aβ) phagocytosis and DNAX activating protein of 12 kDa (Dap12)/Spleen tyrosine kinase (Syk) pathway with modulating disease-associated microglial transcriptional programs.

CONCLUSION: This study identified HP as a strong candidate mediator linking obesity to AD pathogenesis through inhibiting the phagocytosis of Aβ by microglia.},
}

*Alzheimer Disease/genetics/metabolism
*Haptoglobins/metabolism/genetics
*Microglia/metabolism
*Obesity/complications/metabolism/genetics
Humans
*Amyloid beta-Peptides/metabolism
*Phagocytosis/physiology
Animals
Multiomics
Body Mass Index
Female
Male

@article {pmid42634167,
year = {2026},
author = {Singh, K and Narayan, S and Sethi, P and Jain, D and Gupta, JK and Sharma, MC and Shrivastava, A},
title = {Exploring the Therapeutic Potential of Bioactive Peptides in Modulating Tau Protein Interactions via the PI3K/Akt Pathway in Neurodegenerative Diseases.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240423631251207115337},
pmid = {42634167},
issn = {1875-5666},
abstract = {Neurodegenerative Diseases (NDs) represent a growing global health challenge, characterized by progressive neuronal loss and cognitive decline. Central to these disorders are tauopathies, characterized by abnormal aggregation and hyperphosphorylation of tau proteins, leading to synaptic dysfunction and neuronal degeneration. Among the many intracellular signaling pathways implicated in these processes, the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway plays a pivotal role in neuronal survival, synaptic plasticity, and tau phosphorylation regulation. Dysregulation of this pathway exacerbates oxidative stress, inflammation, and excitotoxic injury, thereby accelerating neurodegeneration. Recent research has highlighted the therapeutic potential of bioactive peptides in modulating tau pathology by targeting the PI3K/Akt cascade. These peptides, derived from natural food sources, marine organisms, and microbial fermentation, exhibit neuroprotective effects through multiple mechanisms, including inhibition of tau aggregation, suppression of proinflammatory mediators, enhancement of antioxidant defenses, and modulation of gut microbiota. Evidence from preclinical studies demonstrates that peptides such as curcumin-derived analogs, resveratrol, and glucagon-like peptide-1 analogs reduce tau phosphorylation and restore neuronal integrity. Furthermore, their ability to interact with signaling molecules such as GSK-3β underscores their promise as disease-modifying agents. Despite these advances, challenges remain, including low bioavailability, rapid metabolism, and limited capacity to cross the blood-brain barrier. Emerging nanotechnology-based delivery systems may overcome these barriers, enhancing peptide stability and therapeutic efficacy. This review summarizes current insights into the molecular interactions between bioactive peptides and tau proteins via the PI3K/Akt pathway and highlights their potential as innovative therapeutic agents for neurodegenerative diseases.},
}

@article {pmid42634185,
year = {2026},
author = {Kaymaz, TT and Aşiret, GD and Yüksel, A},
title = {Perceptions of Alzheimer's Disease Among Cognitively Healthy, Community-Dwelling Older Adults: A Metaphor Study.},
journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society},
volume = {26},
number = {5},
pages = {e70212},
doi = {10.1111/psyg.70212},
pmid = {42634185},
issn = {1479-8301},
mesh = {Humans ; *Alzheimer Disease/psychology ; Female ; Aged ; Male ; *Metaphor ; Aged, 80 and over ; Qualitative Research ; Independent Living/psychology ; *Attitude to Health ; Surveys and Questionnaires ; Cognition ; *Health Knowledge, Attitudes, Practice ; },
abstract = {BACKGROUND: Alzheimer's disease prevalence has risen. Although public perceptions of AD may influence attitudes toward cognitive decline and help-seeking behaviours, little is known about how cognitively healthy older adults conceptualise the disease. This study explored older adults' metaphorical perceptions of Alzheimer's disease.

METHODS: This qualitative study employed a phenomenological design using metaphor analysis. Participants were 196 cognitively healthy, community-dwelling older adults. Data were collected using a researcher-developed questionnaire including sociodemographic questions and the prompt, 'Alzheimer's disease is like … because …' Content analysis was used to identify and categorise metaphors.

RESULTS: A total of 196 valid metaphors were identified and organised into four categories: Change and Loss, Hopelessness, Care Dependency and No Return Journey. Participants predominantly described Alzheimer's disease through metaphors reflecting memory and identity loss, helplessness, dependence on care and irreversible cognitive decline, indicating predominantly negative perceptions of the disease among cognitively healthy older adults.

CONCLUSION: The findings suggest that cognitively healthy older adults understand Alzheimer's disease not only as a biomedical condition but also through culturally shared metaphorical meanings centred on loss, dependency and irreversibility. These perceptions may shape attitudes toward dementia before clinical diagnosis and highlight the importance of community-based educational initiatives that address both factual knowledge and stigma surrounding Alzheimer's disease.},
}

Humans
*Alzheimer Disease/psychology
Female
Aged
Male
*Metaphor
Aged, 80 and over
Qualitative Research
Independent Living/psychology
*Attitude to Health
Surveys and Questionnaires
Cognition
*Health Knowledge, Attitudes, Practice

@article {pmid42634196,
year = {2026},
author = {Singh, NK and Oriquat, G and Jain, I and Chaudhary, M and Khlyl, YM and Tailor, NK},
title = {Ferulic Acid and Brain Health: A Defender Against Alzheimer's Disease, Parkinson's Disease, and Neuroinflammation.},
journal = {Current topics in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680266493487260611111705},
pmid = {42634196},
issn = {1873-4294},
abstract = {Neuroinflammation is the body's immune reaction that occurs inside the central nervous system to keep brain cells balanced and healthy. Uncontrolled and chronic neuroinflammation can start damaging neuronal cells and lead to neurodegenerative diseases. Glial cells, especially microglia and astrocytes, play an important role in this process. Microglia act as immune guards of the brain, shifting between protective and harmful states depending on certain signals such as NADPH oxidase 2, histone deacetylases, and transforming growth factor. Astrocytes support neurons and maintain the blood-brain barrier. During injury or stress, they become overactive and release numerous chemicals that make inflammation worse. Further, neuroinflammation is controlled by several signalling pathways, including NF-κB, PI3K/Akt, and MAPK. When these systems lose their balance, they cause ongoing inflammation and oxidative stress, which eventually harm brain cells. During the progression of neurodegenerative disorders, especially Alzheimer's Disease (AD) and Parkinson's Disease (PD), overactive microglia and astrocytes release large amounts of cytokines, reactive oxygen species, and inflammasome components that speed up neuron loss. The constant interaction between NF-κB, NLRP3, and oxidative stress worsens this damage, linking faulty molecular signals with the progression of these disorders. Ferulic acid, a natural antioxidant found in grains, fruits, and vegetables, has shown remarkable protective effects on the brain. It is biologically synthesized from aromatic amino acids L-phenylalanine and L-tyrosine through the shikimate pathway. By clearing free radicals and stopping lipid damage, ferulic acid protects neurons from degeneration. Experimental studies have shown that ferulic acid offers significant antioxidant and anti-neuroinflammatory effects and prevents the accumulation of harmful proteins, such as Aβ and α-synuclein, in the brain. Furthermore, ferulic acid has a strong capacity to modulate several cellular and molecular signaling pathways, including Nrf2/HO-1, NF-κB, and MAPK, which are closely linked to the development and progression of neurodegenerative disorders such as AD and PD. Interestingly, ferulic acid inhibits the generation of pro-inflammatory mediators, ameliorates mitochondrial dysfunction, prevents apoptosis, and consequently protects cholinergic and dopaminergic neurons in the brain, thereby exhibiting remarkable neuroprotective effects. Thus, the current review addressed that ferulic acid is considered a promising natural compound that could be an alternative natural phytoconstituent for the prevention and management of neuroinflammationassociated neurodegenerative disorders like AD and PD.},
}

@article {pmid42634201,
year = {2026},
author = {Chaudhary, G and Paliwal, D and Thakur, A and Gulati, HK and Kaushik, N and Yadav, A},
title = {Thiazole-based Small Molecules as Potential Anti-Alzheimer's Agents: SAR and Mechanistic Insights.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575503002260812070415},
pmid = {42634201},
issn = {1875-5607},
abstract = {A progressive neurodegenerative disease, Alzheimer's Disease (AD), is typified by cognitive decline, synaptic malfunction, and permanent death of neurons. It has a complicated etiology that includes oxidative stress, neuroinflammatory cascades, and monoamine oxidase dysregulation; therapies are limited in their long-term efficacy. This highlights the necessity for carefully crafted multi-target medicines that can modulate multiple pathogenic pathways at once. The advantageous electronic characteristics and structural flexibility of thiazole and benzothiazole derivatives make them appealing, as they can penetrate the blood-brain barrier and serve as heterocyclic scaffolds in medicinal chemistry. According to recent studies, thiazole-based drugs have a strong inhibitory effect against butyrylcholinesterase and acetylcholinesterase, increasing the availability of acetylcholine in synapses. Monoamine oxidase-B (MAO-B) is also strongly and selectively inhibited by several derivatives, which helps to lower oxidative stress and promote neuroprotection. Significantly affecting enzyme affinity, selectivity, and multitarget engagement are structural alterations such as halogen substitution, methoxy incorporation, hydrazone connections, and sulfonamide or piperazine moieties. Beyond enzyme modulation, thiazole-containing molecules interfere with Aβ aggregation, disrupt β-sheet fibril formation, and demonstrate antioxidant and metal-chelating properties. These combined biological effects position thiazole derivatives as potentially disease-modifying multitarget- directed ligands. According to an analysis of the evaluated research, the most effective anti- Alzheimer effects were found in thiazole and benzothiazole derivatives with halogen, methoxy, hydrazone, piperazine, and sulfonamide substituents. Many substances showed nanomolar to low micromolar inhibition of AChE, BuChE, and MAO-B while concurrently inhibiting oxidative stress and amyloid-β formation. Studies on the structure-activity link have shown how crucial strategic substitution patterns are for improving potency, selectivity, and multitarget engagement. This research highlights the feasibility of using thiazoles as scaffold pharmacophores for developing novel drugs to treat Alzheimer's disease and provides vital guidance on the development of future drugs. This review is a comprehensive compilation of small thiazoles being studied for AD with emphasis on structure-activity relationships, molecular targets, and multitarget therapies. This review provides useful information for the rational design of next-generation anti-Alzheimer drugs. It highlights prospective directions for future drug discovery research by methodically outlining current achievements in thiazole-derived AChE, BuChE, MAO-B, and amyloid-β inhibitors.},
}

@article {pmid42634203,
year = {2026},
author = {Khan, MS and Ashesh, AM and Mammen, MV and Alhusaini, A and Jawaid, T and Akhtar, MS and Orayj, K and Ansari, I and Kumar, D and Kumar, A},
title = {Targeting NMDA Receptor Pathways in Alzheimer's Disease, From Cellular Mechanisms to Treatment Strategies.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X474645260731070203},
pmid = {42634203},
issn = {1875-6190},
abstract = {The Alzheimer's Disease (AD) lacks effective disease-modifying therapy, even though amyloid-targeting immunotherapies have recently been applied clinically. N-methyl-D-Aspartate Receptors (NMDARs) play a central yet mechanistically complicated role in the pathophysiology of AD, where they are convergence points of amyloid-beta (Aβ) oligomer toxicity, tau-dependent excitotoxicity, and progressive synaptic failure. This critical review examines NMDAR dysfunction across the AD spectrum, with a focus on subunit-regulated signalling, subcellular localisation, and subsequent pathological cascades. The effects of Aβ oligomers on NMDAR activity involve multiple mechanisms that disrupt their function, including glutamate dysregulation mediated by GLT-1, redistribution of GluN2B to extrasynaptic areas, and inhibition of JAK2-CREB via activation of extrasynaptic receptors. Tau enhances excitotoxic injury throughdendritic mislocalization, and the tau-Fyn-GluN2B complex, which propels pro-death signalling by DAPK1. This conceptually important prevailing synaptic-extrasynaptic dichotomy is fiercely criticised here, given evidence that synaptic receptors containing GluN2A also mediate pathological signalling during sustained Aß exposure, and that tri-heteromeric receptor populations are problematic for subunit-selective targeting. Neuroinflammation, dysfunction of the blood-brain barrier, and excitotoxic amplification via GluN2C/D-enriched receptor pools in neurons, astrocytes, microglia, oligodendrocytes, and endothelial cells are underexplored therapeutic targets for neurodegenerative disease (non-neuronal NMDARs). Memantine is the only approved NMDAR-targeting agent for AD. Subunit-selective antagonists have not been translated into clinical use, and the positive allosteric modulator dalzanemdor (SAGE-718) did not pass its randomised Phase 2 trial in 2024. The most mechanistically justified approach is to advance subunit-selective, compartment-specific, or protein-complexdisrupting strategies. Although it is not established whether any single NMDAR-targeting intervention will suffice as a disease-modifying therapy, the convergence of molecular, genetic, and clinical evidence positions NMDAR dysfunction as a tractable , if therapeutically demanding , node in the AD pathogenic network, warranting continued, mechanism-informed drug discovery.},
}

@article {pmid42634303,
year = {2026},
author = {Sonji, G and Sonji, N and El Katerji, A},
title = {Orexin Signaling, Glymphatic Clearance, and Preclinical Alzheimer's Disease: A Scoping Review and Hypothesis-Generating Conceptual Framework.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050487100260727051112},
pmid = {42634303},
issn = {1875-5828},
abstract = {INTRODUCTION: Sleep fragmentation is associated with preclinical Alzheimer's disease (AD) and may precede cognitive symptoms by years. Sleep disruption is a factor amenable to objective assessment. Evidence suggests that fragmented sleep impairs the brain's glymphatic clearance system, promoting amyloid-beta and tau accumulation. This raises the possibility that dual orexin receptor antagonists (DORAs) may influence sleep-related processes in preclinical AD, though direct human evidence is lacking.

METHODS: This study conducted a PRISMA-ScR scoping review from 2012 to June 2025 evaluating plasma p-tau217, Aβ42/40 ratios, DTI-ALPS, sleep architecture, and APOE ε4 genotype. This study assessed evidence quality using an exploratory confidence-rating approach.

RESULTS: In some transgenic AD models, orexin antagonism reduced amyloid plaque burden. Human data remain limited. In a randomized placebo-controlled four-week trial involving 285 participants with probable AD dementia and insomnia, suvorexant significantly increased total sleep time relative to placebo. However, biomarker changes, glymphatic function, and long-term cognitive outcomes were not evaluated. Thus, current evidence for disease-modifying effects in humans is very limited and uncertain.

DISCUSSION: Whether DORAs influence glymphatic clearance in humans remains unknown. One untested mechanistic question concerns the role of noradrenergic vascular pulsations during sleep. Future trials should incorporate integrated endpoints including fluid biomarkers, neuroimaging, and sleep physiology.

CONCLUSION: Preclinical findings remain preliminary and lack human validation. This review maps existing biomarker literature to generate mechanistic hypotheses; no integrative risk model, threshold combination, or stratification tool is proposed. Mechanistic proof-of-concept studies must precede any consideration of larger trials or translational application.},
}

@article {pmid42634308,
year = {2026},
author = {Peng, Y and Ye, T and Qi, D and Cheng, X},
title = {Effects Of Ethanol on the Structure and Function of the BBB and Their Roles in Central Nervous System Diseases.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575464650260731052107},
pmid = {42634308},
issn = {1875-5607},
abstract = {The blood-brain barrier (BBB) plays a vital role in maintaining brain homeostasis, as its proper function and structural integrity are essential. Communication between endothelial cells and nearby perivascular cells, which include pericytes, astrocytes, microglia, and oligodendrocytes, is key to the overall structure and function of the BBB. When ethanol is consumed, it raises the permeability of the BBB, leading to significant damage that can adversely affect brain health. This article reviews how ethanol interacts with the body, detailing the various mechanisms through which it alters the BBB's structure and function. We particularly highlight how ethanol damages endothelial cells, activates astrocytes and microglia, disrupts the differentiation and survival of oligodendrocyte precursor cells (OPCs), triggers neuroimmune responses, inhibits glucose transport, modifies blood pressure, and increases blood flow. Moreover, we examine how different levels of ethanol consumption influence the risk of developing conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. Interestingly, moderate alcohol intake may lower the odds of these diseases, while excessive drinking can heighten the risk. The effects of ethanol exposure on BBB permeability can also vary due to factors like sex, age, and genetics. Research suggests that estrogen is important for preserving the integrity of the BBB and protecting against neural damage, whereas high levels of ethanol intake may worsen BBB impairment, especially in individuals with the ApoE4 genotype. In summary, this article focuses on the mechanisms by which ethanol impacts the BBB, with the goal of offering insights that could assist in preventing and treating central nervous system diseases, particularly AD.},
}

@article {pmid42634328,
year = {2026},
author = {Gi, Y and Lim, H and Jung, AH and Lee, J and Park, S and Baek, SH and Kim, JH and Kim, BJ and Yoon, M},
title = {Regional Fractal Dimension as a Complementary Morphometric Marker in Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050509238260717071733},
pmid = {42634328},
issn = {1875-5828},
abstract = {INTRODUCTION: Fractal Dimension (FD) has been proposed as a marker of structural complexity in Alzheimer's Disease (AD), but its regional distribution and complementary value beyond conventional morphometry remain unclear. This study investigated whether regional FD captures AD-related structural alterations distinct from regional volume and thickness.

METHODS: Using T1-weighted MRI from ADNI1, with external validation in MIRIAD and NACC, we extracted 79 cortical, subcortical, and CSF-related regions and computed volume, thickness, and FD for each region. We assessed covariate-adjusted disease-stage associations, residual FD after linear and nonlinear adjustment for morphometric and demographic factors, clinical associations, and classification performance using conventional features, FD alone, or their combination.

RESULTS: FD showed localized, region-dependent alterations, particularly in the hippocampus, ventricular structures, and caudate. In linear residual analysis, FD associations remained strongest in the bilateral inferior lateral ventricles and left caudate after morphometric and demographic adjustment. Nonlinear adjustment attenuated the ventricular associations, suggesting sensitivity to nonlinear size-shape effects, whereas the left caudate remained consistently associated with diagnostic stage. Adjusted FD also showed modest but significant associations with clinical measures. Combining FD with volume and thickness showed modest additive classification utility.

DISCUSSION: Regional FD captures selected aspects of structural complexity that are not fully represented by volume or thickness under the tested framework. Ventricular FD appears sensitive to nonlinear size-shape effects, whereas caudate FD may provide more stable residual information.

CONCLUSION: Regional FD provides complementary, region-dependent morphometric information in AD and should be interpreted as an additive descriptor rather than a standalone biomarker.},
}

@article {pmid42634335,
year = {2026},
author = {Langmead, AP and Keane, BA and Jacob, JA and Ramana, KV},
title = {Metformin in Neurodegenerative Diseases: Mechanisms and Therapeutic Implications.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X476604260704180015},
pmid = {42634335},
issn = {1875-6190},
abstract = {As the global burden of neurodegenerative disorders continues to rise with aging populations, there is growing interest in identifying widely available drugs that can be repurposed to target shared metabolic and inflammatory mechanisms underlying these conditions. Increasing evidence suggests that metabolic dysfunction, mitochondrial impairment, and chronic neuroinflammation play central roles in the pathogenesis of neurodegeneration, demonstrating the need for therapeutics that can modulate these interconnected pathways. Metformin has served as the gold standard for the management of type 2 diabetes for 7 decades. It offers a superior safety profile, established metabolic advantages, and affordability. Recent studies suggest that, in addition to its antihyperglycemic actions, it could also be repurposed to treat several inflammatory complications and infectious diseases. Further, recent preclinical and clinical studies suggest that, by regulating AMPK, mTOR, and mitochondrial function, metformin could also control the initiation and progression of neurodegenerative diseases. Several studies also indicate that metformin suppresses neuroinflammation by inhibiting the NF-κB signaling pathway and the NLRP3 inflammasome, thereby improving insulin signaling and metabolic homeostasis. This review integrates metabolic, inflammatory, and mitochondrial mechanisms to present a unified mechanistic framework to explain how metformin may modulate the onset and progression of neurodegeneration. Specifically, we discuss recent studies showing the therapeutic significance of metformin in Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Moreover, this review highlights metformin as a potential therapeutic candidate for future development in neurodegenerative diseases.},
}

@article {pmid42634340,
year = {2026},
author = {Cui, H and Li, Q and Yao, Y and Wang, X and Tian, S},
title = {Physicochemical Characterization and Biological Activity of Ethanol- Extracted Residue of Saussurea involucrata.},
journal = {Combinatorial chemistry & high throughput screening},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113862073470898260602093207},
pmid = {42634340},
issn = {1875-5402},
abstract = {INTRODUCTION: Saussurea involucrata's ethanol-extracted residue (ROSI), a byproduct of its oral liquid preparation, nevertheless holds significant therapeutic promise. To evaluate its potential as a treatment for neurodegenerative illnesses, this study investigates its physicochemical properties and biological activity.

MATERIALS AND METHODS: UV-Vis, IR spectroscopy, UHPLC-Q Exactive HFX systems, microscopy, powder characterisation, and thermogravimetric analysis were used to examine the physical and chemical characteristics of ROSI. Antioxidant activities and pancreatic lipase inhibition were assessed. Its therapeutic targets for neurodegenerative disorders were predicted by network pharmacology and molecular docking analyses.

RESULTS: ROSI demonstrated high organic acid content, a uniform porous structure, consistent particle size, and high thermal stability, meeting industrial flowability standards. While showing modest pancreatic lipase inhibition, it exhibited potent antioxidant activity. Pharmacomics analysis suggests ROSI may target multiple pathways involved in neurodegenerative diseases.

DISCUSSION: Despite its modest pancreatic lipase inhibitory effect, ROSI exhibits potent antioxidant activity and stable physicochemical properties suitable for industrial applications. Network pharmacology and molecular docking analyses reveal therapeutic potential for ROSI in neurodegenerative diseases such as Alzheimer's and Parkinson's. Consequently, ROSI serves as a natural antioxidant and a raw material for the development of functional foods and pharmaceuticals.

CONCLUSION: ROSI holds promise as an adjunctive treatment for neurodegenerative diseases, particularly for its antioxidant effects and industrial applicability. Further research should optimize its use in chronic disease management and explore its broader medicinal potential.},
}

@article {pmid42634350,
year = {2026},
author = {Zulfqar, I and Masaud, SM and Bukhari, A and Anwar, T and Hamid, H and Khan, MI and Abbas, M and Nadeem, H},
title = {Design, Synthesis, In Silico and In Vitro Analysis of Newly Synthesized 2-Mercaptobenzazole Derivatives as Potential Acetylcholinesterase Inhibitors.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673475170260728043412},
pmid = {42634350},
issn = {1875-533X},
abstract = {INTRODUCTION/BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cholinergic dysfunction and excessive oxidative stress. Targeting acetylcholinesterase (AChE) alongside antioxidant mechanisms represents a rational multitarget therapeutic strategy. The present study aimed to design, synthesize, and evaluate a new series of 2-mercaptobenzimidazole derivatives as potential dual-acting anti-Alzheimer agents.

METHODS: A series of eight novel 2-mercaptobenzimidazole derivatives (2a-2h) was synthesized through a two-step synthetic route involving acylation of substituted amines with chloroacetyl chloride, followed by coupling with 2-mercaptobenzimidazole. Structural elucidation was performed using standard spectroscopic techniques. in silico ADMET profiling and molecular docking were conducted against human AChE (PDB ID: 4EY7). The compounds were further evaluated for in vitro AChE inhibitory activity, enzyme kinetics, and antioxidant potential using the DPPH radical scavenging assay.

RESULTS: ADMET analysis predicted favorable drug-like characteristics, including acceptable physicochemical properties, good intestinal absorption, and low hepatotoxicity risk. Molecular docking studies revealed enhanced binding affinity for derivatives bearing electron-withdrawing substituents, with compound 2d demonstrating the strongest interaction (-10.6 kcal/mol) through π-π stacking and hydrogen bonding within the active site. in vitro AChE inhibition assays supported the computational findings, where compounds 2c (IC50 = 12.9 ± 0.7 μM) and 2h (IC50 = 15.1 ± 0.9 μM) exhibited promising activity relative to Donepezil. Kinetic analysis confirmed mixed- type inhibition by compound 2c, yielding a Km of 51.6 ± 1.5 μM, a Vmax of 0.61 ± 0.03 μmol/min/mg, and a Ki value of 6.8 ± 0.4 μM. Antioxidant evaluation indicated notable DPPH radical scavenging activity, with compound 2h showing 79.69% inhibition at 50 μg/mL.

DISCUSSION: The consistency between molecular docking, enzyme inhibition, and kinetic findings suggests that substituent-driven interactions play an important role in AChE inhibition. Additionally, the observed antioxidant activity highlights the therapeutic potential of these derivatives as multitarget agents capable of addressing both cholinergic dysfunction and oxidative stress associated with AD.

CONCLUSION: Collectively, the synthesized 2-mercaptobenzimidazole derivatives demonstrated promising acetylcholinesterase inhibitory and antioxidant properties. These findings support their potential as lead scaffolds for the development of novel multitarget therapeutic candidates for Alzheimer's disease.},
}

@article {pmid42634351,
year = {2026},
author = {Patnaik, S and Patra, PK and Patra, CN and Panda, KC},
title = {Biomarkers, Diagnostics, and Emerging Therapies in Alzheimer's Disease: A Comprehensive Systematic Review (2015-2025).},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249427154260531181405},
pmid = {42634351},
issn = {1875-6166},
abstract = {INTRODUCTION: The underlying association between multiple risk factors like age, preexisting diseases, infections, traumatic brain injuries, and certain genetic factors makes the diagnosis and treatment a challenge in AD. Identification of biomarkers and proper diagnosis of AD could make its management easier. Advances in diagnostic techniques like Positron Emission Tomography (PET) imaging have greatly improved the ability to identify, detect early, monitor disease progression, and manage its therapy.

METHODS: The recent therapeutic advancements in treatments encompass immunotherapies aimed at amyloid-beta (Aβ) and tau proteins, novel drug delivery systems, non-pharmacological methodologies, and personalised medicine techniques, combination therapies, and non-invasive brain stimulation are important in the management of AD. Cholinesterase inhibitors, such as galantamine, rivastigmine, and donepezil, are used to enhance cognitive performance and reduce confusion. Moderate to severe AD, memantine, a N-methyl-D-aspartate receptor (NMDA) receptor antagonist, is prescribed. Researchers are looking into both active and passive vaccines to get antibodies to Aβ plaques, and monoclonal antibodies, such as Lecanemab and Donanemab, which are used to treat early-stage AD.

RESULTS: Ongoing research is focused on identifying new biomarkers and therapeutic targets, advancing gene therapy, and refining immunotherapeutic approaches for AD.

DISCUSSION: There is growing interest in comprehending the influence of lifestyle and environmental factors on the mitigation of AD risk. Ongoing research is essential to elucidate the complexity of AD pathophysiology and to create effective therapies.

CONCLUSION: This review highlights the critical need for future AD research to bridge identified gaps in early detection, focus on improving early diagnosis, developing more effective treatments, refining existing drugs and therapies, and understanding the underlying disease progression mechanisms.},
}

@article {pmid42634371,
year = {2026},
author = {Güneşli, A and Hussein, F},
title = {Subclinical Atherosclerosis Markers in Alzheimer's and Vascular Dementia: A Cross-Sectional Comparison with Healthy Controls.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050495193260728050343},
pmid = {42634371},
issn = {1875-5828},
abstract = {INTRODUCTION: Vascular mechanisms are increasingly implicated in the pathophysiology of Alzheimer's disease and vascular dementia. This study aimed to evaluate the association between subclinical atherosclerosis markers and cognitive performance in patients with Alzheimer's disease and vascular dementia compared with healthy controls.

METHODS: This cross-sectional study included 79 patients with Alzheimer's disease, 69 patients with vascular dementia, and 69 age- and sex-matched controls. Vascular markers were measured, and cognitive function was assessed using the Mini-Mental State Examination. Correlation, multivariable regression, and receiver operating characteristic analyses were performed.

RESULTS: The dementia groups had greater epicardial fat thickness (Alzheimer's disease: 6.49 ± 0.93 mm; vascular dementia: 6.36 ± 1.04 mm) than controls (5.77 ± 0.87 mm, p < 0.001). Carotid intima- media thickness was higher (0.53 ± 0.08 mm and 0.55 ± 0.10 mm versus 0.48 ± 0.08 mm, p < 0.001). Carotid distensibility and strain were lower in dementia (0.21 ± 0.03 and 10.26 ± 1.58; 0.21 ± 0.03 and 9.93±1.77) than in controls (0.25 ± 0.05 and 11.3 ± 1.75, p < 0.05). Mini-Mental State Examination scores correlated negatively with epicardial fat thickness (r = -0.30) and carotid intima- media thickness (r = -0.27), and positively with distensibility (r = 0.40) and strain (r = 0.31). Epicardial fat thickness (area under the curve 0.716) and carotid intima-media thickness (0.678) showed moderate ability to distinguish dementia from controls.

DISCUSSION: These findings support a significant association between vascular structural and functional alterations and cognitive impairment.

CONCLUSION: Subclinical atherosclerosis markers were significantly associated with cognitive impairment; however, causal relationships cannot be inferred due to the cross-sectional design. These markers may support early identification and risk stratification of dementia.},
}

@article {pmid42634372,
year = {2026},
author = {Tong, Y and Hu, G and Liu, L and Zhang, Y and Jiang, N and Hou, Y and Zhang, M},
title = {Dynamic Entropic Mapping of Alzheimer's Neuropathology: Eyes-Open and Eyes-Closed EEG Biomarkers through Wavelet Entropy Analysis.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050450560260119050625},
pmid = {42634372},
issn = {1875-5828},
abstract = {BACKGROUND: Alzheimer's Disease (AD) is characterized by amyloid-β plaques and tau tangles, while current diagnostic tools are often invasive and costly. Electroencephalography (EEG) offers a non-invasive alternative, with alpha rhythm abnormalities as key features. Impaired alpha reactivity during the transition from Eyes-Closed (EC) to Eyes-Open (EO) reflects early thalamocortical dysfunction.

OBJECTIVE: This study employs EO/EC wavelet entropy analysis to assess neurodynamic features across frequency bands, aiming to explore entropy-based EEG markers for early AD detection.

METHODS: This cross-sectional study enrolled 60 participants (30 AD and 30 controls). EEG was recorded during 60-second EC and Eyes-Open (EO) states using a 20-channel system. Continuous Wavelet Transform (CWT) and multiscale entropy were used to assess complexity differences across bands and regions between groups.

RESULTS: AD patients showed reduced alpha entropy differences between EC and EO states. Multiscale entropy difference (ΔEN α) analysis revealed weaker modulation in β-α and θ-δ bands compared with HC. Occipital ΔEN α correlated significantly with MMSE, with the strongest association in the alpha band (r = 0.9000, P < 0.001).

DISCUSSION: This study applies dual-state wavelet entropy analysis to reveal impaired neural reactivity in AD during eyes-open and eyes-closed transitions. The ΔEN α metric distinguishes AD from controls and correlates with cognitive decline, reflecting reduced neural flexibility and disrupted frequency-specific network dynamics.

CONCLUSION: This study shows that dual-state wavelet entropy analysis, especially ΔEN α, is a noninvasive tool for detecting neurodynamic abnormalities in AD. It reflects loss of state-dependent responsiveness and neural complexity, with potential for early screening and objective evaluation of treatment.},
}

@article {pmid42634511,
year = {2026},
author = {Mishra, R and Chauhan, N and Agrawal, KK},
title = {Current Targeted Nanoparticle Therapy for Alzheimer's Disease: Current Advances and Future Prospects.},
journal = {Current neurovascular research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672026471444260724103751},
pmid = {42634511},
issn = {1875-5739},
abstract = {BACKGROUND: The effects of Alzheimer's disease (AD) on society are profound. The blood-brain barrier selectively permits the penetration of specific forms of molecules through the blood circulation into the CNS, which can restrict the effectiveness of medications supplied systemically. The therapeutic targets are located in the CNS. However, local administration channels to the CNS are rather intrusive, which can lead to patient discomfort and limit the feasibility of repeated treatments.

METHODOLOGY: This article has evaluated treatment methodologies for AD that use nanoparticles to target the brain and the pathological features of the illness. The material that is currently available has been categorized based on the aspect of AD that is discussed: targeted medication and neurodegeneration.

RESULT: The use of nanoparticles in the targeted delivery of medications intended to alleviate the symptoms of AD or halt the disease's progression has yielded positive results. Because of their multivalence, nanoparticles can target the treatment site, pass through the blood-brain barrier, and be functionalized with various targeting groups. Intravenous administration, rather than more intrusive techniques, has enhanced drug bioavailability in the CNS. Furthermore, the development of vaccinations and medication formulations for intranasal delivery has utilized nanoparticles.

DISCUSSION: This study focused on the advancement of AD treatment. Nanoparticles are designed to enhance drug bioavailability through intravenous and intranasal routes for quicker brain access with fewer side effects. Nanoparticles also aid in targeting disease features like amyloid- beta plaques and tau tangles. While results in animal models are positive, transitioning to human clinical trials requires a more profound understanding of AD mechanisms and biomarker identification.

CONCLUSION: Research employing animal models suggests that targeted nanoparticles can enhance the effectiveness of AD treatments. A deeper understanding of AD mechanisms will lead to more successful targeted nanoparticle applications.},
}

@article {pmid42634521,
year = {2026},
author = {Motamedi, S and Karimi, I},
title = {The Black Hole of the Brain: A Novel Energy-Based Therapeutic Perspective for Alzheimer's Disease.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050438652260723053125},
pmid = {42634521},
issn = {1875-5828},
abstract = {Alzheimer's Disease (AD) is considered a devastating and often underrecognized global health burden. Despite extensive ongoing research, effective treatments remain limited by an incomplete understanding of its multifarious pathogenesis, more than a century since the first report of AD in 1906. This review proposes a novel conceptual framework that draws parallels between entropy- driven systemic collapse in physical systems and neurodegeneration in AD. Specifically, it highlights how entropy may lead to systemic collapse, whether in a dead star that forms a black hole or in an AD-afflicted brain region. Though differing in biological and physical scales, AD and black holes share analogous features, including rising entropy, irreversible degeneration, and system decay, that are fundamental to understanding their underlying physics. Both AD and black holes represent systems characterized by irreversible loss of structure, energy, and information. In AD, progressive neural death leads to cognitive impairment, synapse loss, and brain atrophy, reflecting impaired energy utilization and increasing entropy within neural networks. Similarly, a black hole forms from stellar collapse, where energy becomes gravitationally confined and entropy increases as information is lost beyond the event horizon. Diagnostic exploration of both phenomena relies on interpreting waves and signals, neuroimaging in the brain, and the detection of electromagnetic or gravitational waves in space, revealing how the breakdown of structure and the dissipation of accessible energy signify a fundamental loss of order in complex systems. This conceptual framework may help inspire innovative energy-based therapeutic approaches for AD before the disease reaches an irreversible stage of pathogenesis.},
}

@article {pmid42634522,
year = {2026},
author = {Martinez, LD and Ortiz Rojas, HJ and Loaiza, JHI and Terranova, DA and García, F and Satizabal, JM},
title = {Descriptive Analysis of Genetic Variants in Individuals Without a Clinical Diagnosis of Alzheimer's Disease in a Population from Southwestern Colombia.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050477248260724105245},
pmid = {42634522},
issn = {1875-5828},
abstract = {INTRODUCTION: Alzheimer's Disease (AD) is the most common cause of dementia worldwide and a chronic neurodegenerative disorder with well-established pathophysiological mechanisms. In Colombia, its prevalence is increasing, but in the southwestern region, information on its clinical course is scarce, limiting adequate care and public health strategies. This study aimed to describe the frequency and characteristics of genetic variants in AD candidate genes in a population in southwestern Colombia without a clinical diagnosis of the disease.

METHODS: A descriptive observational analysis was conducted on 320 whole exomes from patients without a clinical diagnosis of AD. Reported genomic variants in the APOE, ABCA7, APP, PSEN1, PSEN2, and CLU genes were examined for allele frequency, clinical significance, and interaction network predictions to assess their genetic impact on the population.

RESULTS: We identified 294 genetic variants, including 267 previously unreported. Among the 27 variants reported in ClinVar, most lacked a definitive clinical interpretation and were classified as Variants of Uncertain Significance (VUS) or as variants without a defined clinical significance in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). ABCA7 gene had the highest frequency of variants (n=164), and the PSEN1 gene had the lowest (n=14). While most variants lacked clinical significance, the APOE c.487C>T (p.Arg163Cys) variant was identified as likely pathogenic.

DISCUSSION: The genetics of AD are complex and contribute to a predisposition to developing the disease; hence, the importance of conducting studies in our Colombian population, which is characterized by great genetic variability. In our study, we identified 267 unreported variants associated with the genes APOE, ABCA7, APP, PSEN1, PSEN2, and CLU. The lack of updated data in our population underscores the need for further research to determine their clinical impact.

CONCLUSION: This research contributes to characterizing AD genetic variability in the Colombian population and identifies several previously unreported variants. According to our results, we recommend studying their potential functional and clinical impact to improve early diagnosis and support the development of targeted therapies, thereby contributing to a better understanding of the disease in southwestern Colombia.},
}

@article {pmid42634530,
year = {2026},
author = {Gairola, N and Uniyal, S and Martolia, J and Gogoi, H and Tiwari, N and Joshi, BC},
title = {Neuroprotective Potential of Terpenoids: A Promising Avenue in Neurology.},
journal = {Mini reviews in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113895575463965260727105312},
pmid = {42634530},
issn = {1875-5607},
abstract = {Neurodegenerative diseases are progressive disorders characterised by the deterioration of neuronal structure and function, ultimately leading to cognitive deficits and functional impairment. Due to neuroinflammation, oxidative stress, and mitochondrial dysfunction, neurones, which cannot regenerate themselves, are highly susceptible to degeneration. There are many possible side effects associated with traditional pharmacotherapies, although they often offer symptomatic relief, highlighting the need for safer and more effective therapeutics. Natural products such as terpenoids, a structurally diverse class of isoprenoid compounds, have shown promising neuroprotective effects. Classes of terpenoids exhibit anti-inflammatory, antioxidant, anti-apoptotic, and mitochondrialprotective effects by regulating crucial signalling cascades, including Nuclear Factor kappa B (NF- κB), Mitogen-activated protein kinase (MAPK), c-Jun N-terminal Kinase (JNK), Phosphoinositide 3-kinase/Protein kinase B (PI3K/Akt), and Nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1). Across preclinical models, representative compounds like catalpol, geniposide, artesunate, ginkgolides, alisol A 24-acetate, echinocystic acid, lycopene, and astaxanthin have demonstrated efficacy against Parkinson's disease, Alzheimer's disease, stroke, ischaemia, and haemorrhage by preserving neuronal integrity and function. Despite these promising findings, challenges such as poor bioavailability, limited blood-brain barrier penetration, metabolic instability, and a lack of standardised human safety data limit translational progress. Structural optimisation and advanced delivery systems, such as nanoparticles, cyclodextrin inclusion, combined therapeutic strategies, precision-targeted interventions, and rigorous clinical trials, may be considered future directions. In short, terpenoids have the potential to be developed as novel multitarget neurotherapeutic agents with further research to bridge preclinical promise and clinical validation.},
}

@article {pmid42634550,
year = {2026},
author = {Du, Y and Li, J and Han, F and Li, J and Lin, H and Ge, F},
title = {Safety Comparison of Acetylcholinesterase Inhibitors Using FAERS Spontaneous-Reporting Data: Drug-Specific Reporting Signals and Time-to-Onset Dynamics.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050497124260720115932},
pmid = {42634550},
issn = {1875-5828},
abstract = {INTRODUCTION/OBJECTIVE: Acetylcholinesterase Inhibitors (AChEIs) are widely used for symptomatic treatment of Alzheimer's disease, but their post-marketing reporting profiles may differ. This study compared FAERS disproportional reporting signals and Time-To-Onset (TTO) patterns for donepezil, galantamine, and rivastigmine.

METHODS: FAERS reports from Q1 2004 to Q2 2025 were analyzed. Reports listing donepezil, galantamine, or rivastigmine as the primary suspect drug were retained. Unique case-drug-Preferred Term (PT) triplets were constructed after case-level and drug-event-level de-duplication. Positive signals were defined conservatively by the intersection of ROR, PRR, BCPNN, and MGPS/EBGM criteria. TTO was evaluated using cumulative onset-distribution curves, Weibull models, and Accelerated Failure-Time (AFT) models.

RESULTS: The analysis included 9,474 donepezil reports, 3,042 galantamine reports, and 14,666 rivastigmine reports. The four-method intersection identified 286 positive PT reporting signals for donepezil, 143 for galantamine, and 259 for rivastigmine. Donepezil showed prominent cardiac reporting signals, including sinus bradycardia (ROR = 49.0) and electrocardiogram QT prolongation (ROR = 16.75). Rivastigmine showed application-site signals, including application-site erythema (ROR = 21.36) and application-site pruritus (ROR = 18.07). Galantamine showed signals including bradycardia (ROR = 15.37), fall (ROR = 3.44), and decreased appetite (ROR = 3.57). Median TTOs were 38, 44, and 64 days for donepezil, galantamine, and rivastigmine, respectively. Rivastigmine showed a later reported onset than donepezil in the AFT model (TR = 1.08; p = 0.008).

DISCUSSION: The findings suggest shared cholinergic reporting patterns and drug-specific signal profiles. Because FAERS lacks exposure denominators, these results indicate disproportional reporting rather than incidence, causality, or comparative clinical risk.

CONCLUSION: Donepezil, galantamine, and rivastigmine showed distinct FAERS reporting profiles and early post-initiation TTO patterns. These findings are hypothesis-generating and require confirmation in independent pharmacovigilance or clinical datasets.},
}

@article {pmid42634764,
year = {2025},
author = {Kordi, MR and Kooshan, AR and Jafari-Hokmabadi, SP and Gaeini, AA and Zobeydi, AM},
title = {Combating cognitive decline in a rat model of Alzheimer's disease: The role of high-intensity interval training and cannabidiol administration in modulating microRNA-124, BACE1, and nestin.},
journal = {Current journal of neurology},
volume = {24},
number = {3},
pages = {219-228},
pmid = {42634764},
issn = {2717-011X},
abstract = {Background: The global prevalence of Alzheimer's disease (AD) has emerged as a paramount concern due to the aging population. The current research examines the effects of six-week high-intensity interval training (HIIT), with and without cannabidiol (CBD) supplementation, on cognitive decline, micro ribonucleic acid (miRNA)-124 expression levels, and the protein expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and nestin in the hippocampus of rats with amyloid beta (Aβ)-induced AD. Methods: 30 male Wistar rats were randomly divided into six groups: control (CNT), sham, Alzheimer (AD), Alzheimer + HIIT (H-AD), Alzheimer + CBD (C-AD), and Alzheimer + HIIT + CBD (CH-AD). Following the hippocampal injection of Aβ1-42, the HIIT protocol and CBD supplementation [20 mg/kg/day, per os (P.O.)] were initiated and conducted over six weeks. After the last intervention, the hippocampus tissues were collected to assess miRNA-124 expression levels and the protein expression of BACE1 and nestin. Results: HIIT alone and in combination with CBD treatment significantly improved cognitive impairment induced by AD. Moreover, both treatments significantly reduced BACE1 protein expression and increased nestin protein expression in AD rats. However, despite decreased miRNA-124 expression levels in the AD group in comparison with the CNT group, HIIT and CBD administration did not alter miRNA-124 expression levels in other groups. Conclusion: The findings can contribute to a higher understanding of the beneficial effects of HIIT combined with CBD administration in mitigating AD-induced cognitive impairment by reducing BACE1 protein expression and increasing nestin protein expression.},
}

@article {pmid42634953,
year = {2026},
author = {Du, L and Yan, S and Ren, X and Hassan, SSU and Sun, Y and Gan, Y and Xiao, X and Li, S and Jin, H},
title = {Breaking Alzheimer's Disease Barrier: The Role of Xanthoceras sorbifolia Bunge Oil in Gut-Brain Axis and TLR4/Myd88/MAPK Pathway Inhibition.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70432},
pmid = {42634953},
issn = {1099-1573},
support = {81830117//National Natural Science Foundation of China/ ; 2020YFC2003100//National Key R&D Program of China/ ; U22A20365//Joint Funds of National Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with cognitive decline and neuroinflammation. Xanthoceras sorbifolia Bunge oil (XSBO), a woody plant oil rich in bioactive fatty acids, has shown potential health benefits. This study aimed to investigate the neuroprotective effects and underlying mechanisms of XSBO in AD. A scopolamine-induced AD rat model was established to evaluate the effects of XSBO on cognitive function, pathological changes, and neuroinflammation. Gut microbiota alterations were analyzed by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) and short-chain fatty acid (SCFA) supplementation experiments were performed to explore the role of gut microbiota-derived metabolites. The TLR4/MyD88/MAPK signaling pathway was further examined. XSBO treatment improved cognitive deficits, reduced neuronal damage and neuroinflammation, and enhanced intestinal barrier integrity in AD rats. XSBO restored gut microbiota dysbiosis and increased SCFA-producing bacteria. FMT and SCFA supplementation confirmed that microbiota-derived metabolites contributed to XSBO-mediated cognitive improvement and neuroprotection. Mechanistically, XSBO inhibited lipopolysaccharide-induced neuroinflammation by suppressing TLR4/MyD88/MAPK signaling activation. XSBO alleviates AD-related cognitive impairment and neuroinflammation by modulating the gut microbiota-SCFA axis and inhibiting TLR4/MyD88/MAPK-mediated inflammatory responses. These findings suggest that XSBO may serve as a promising dietary intervention for neurodegenerative disease management.},
}

@article {pmid42634961,
year = {2026},
author = {Tsiknia, AA and Tennant, VR and Davison, M and Nandy, R and Borzage, M and Clark, AL and Toga, AW and Yaffe, K and O'Bryant, S and Braskie, MN and , },
title = {Diabetes and neurodegeneration in cognitively unimpaired older adults: implications for cognition.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag287},
pmid = {42634961},
issn = {1460-2156},
abstract = {Type 2 diabetes mellitus is associated with cognitive impairment and greater Alzheimer's disease risk, with cross-sectional studies suggesting that this is driven by neurodegeneration and vascular changes. Longitudinal studies, however, report similar rates of total brain atrophy over time in diabetic and non-diabetic adults. We recently showed that diabetes-related neurodegeneration in cognitively unimpaired adults is regional and may not be evident in longitudinal studies of global brain atrophy. The mechanisms driving diabetes-related neurodegeneration are unknown; glycemic control may play an important role but the relative influence of Alzheimer's and cerebrovascular pathology is unclear. Here, we longitudinally examined regional patterns of cortical thinning associated with diabetes and glycemic control over nearly 3 years. We controlled for Alzheimer's disease neuropathology and white matter hyperintensity burden. We also examined whether subsequent changes in hemoglobin A1c (HbA1c) levels correlated with rates of cortical thinning in diabetes-associated regions and tested whether faster cortical thinning in diabetes-relevant regions mediated a relationship between diabetes and decline in cognitive performance. Among 1,298 cognitively unimpaired participants (mean age=65.0 years, 305 diabetic, 869 female) from the Health and Aging Brain Study-Health Disparities cohort who completed baseline and follow-up MRI scans, we used linear mixed-effects models to examine the relationship between diabetes and cortical thickness changes across 34 brain regions, controlling for socioeconomic factors and comorbidities. We further adjusted for amyloid-PET, tau-PET, white matter hyperintensities, and APOE ε4 carrier status. We also examined associations between baseline and longitudinal HbA1c levels and cortical thinning rates in diabetes-related regions in the whole sample and separately in diabetic and non-diabetic participants. P-values were corrected using the false discovery rate method. Path analysis tested whether diabetes-related cortical thinning mediated the relationship between diabetes and decline in cognitive performance. Diabetic participants exhibited faster cortical thinning in seven frontal, parietal, and occipital regions (-0.060≤βs≤-0.046, corrected Ps<0.017). Associations remained unchanged after accounting for socioeconomic factors, comorbidities, amyloid, tau, white matter hyperintensities, and APOE ε4. Higher baseline HbA1c predicted faster thinning in diabetes-vulnerable regions (corrected Ps<0.032), independent of subsequent HbA1c changes. Diabetes was associated with faster decline in processing speed (β=-0.022, P=0.033), with cortical thinning in diabetes-related regions mediating approximately 13% of this effect (indirect effect β=-0.034, P=0.019). Diabetes-related cortical thinning in cognitively unimpaired older adults follows a regional pattern independent of Alzheimer's and cerebrovascular pathology and partially mediates accelerated decline in processing speed. Chronic hyperglycemia may contribute to diabetes-related neurodegeneration, regardless of subsequent short-term changes in glycemic control.},
}

@article {pmid42635046,
year = {2026},
author = {Yang, X and Fatima, S and Sampere-Birlanga, S and Ware, A and Shumliakivska, M and Zanders, L and Radhakrishnan, S and Luxán, G and John, D and Günther, S and Mas-Peiro, S and Dimmeler, S and Zeiher, AM and Abplanalp, WT},
title = {Mutation-resolved single-cell transcriptomics reveals enhanced β-amyloid clearance in TET2-mutant human monocytes.},
journal = {JCI insight},
volume = {11},
number = {16},
pages = {},
doi = {10.1172/jci.insight.208804},
pmid = {42635046},
issn = {2379-3708},
mesh = {Humans ; *Monocytes/metabolism/immunology ; *Amyloid beta-Peptides/metabolism ; *DNA-Binding Proteins/genetics/metabolism ; Mutation ; Dioxygenases/genetics ; Single-Cell Analysis ; Single-Cell Gene Expression Analysis ; *Proto-Oncogene Proteins/genetics ; *Alzheimer Disease/genetics/metabolism ; Phagocytosis/genetics ; Transcriptome ; Immunity, Innate/genetics ; Macrophages/metabolism/immunology ; },
abstract = {TET2-driven clonal hematopoiesis has been associated with reduced Alzheimer's disease risk, but mechanisms in humans remain unclear. Using mutation-resolved single-cell transcriptomics, we distinguished TET2-mutant and wild-type monocytes within the same aged individuals and identified enrichment of phagocytosis and complement programs in mutant cells. TET2 silencing in human monocytes and macrophages recapitulated this phenotype and enhanced β-amyloid uptake, indicating mutation-specific bias of innate immunity toward aggregate clearance.},
}

Humans
*Monocytes/metabolism/immunology
*Amyloid beta-Peptides/metabolism
*DNA-Binding Proteins/genetics/metabolism
Mutation
Dioxygenases/genetics
Single-Cell Analysis
Single-Cell Gene Expression Analysis
*Proto-Oncogene Proteins/genetics
*Alzheimer Disease/genetics/metabolism
Phagocytosis/genetics
Transcriptome
Immunity, Innate/genetics
Macrophages/metabolism/immunology

@article {pmid42635075,
year = {2026},
author = {Kumar, A and Kaushik, A and Devi, A and Ankalgi, AD and Ashawat, MS and Alharbi, HM and Amin, M and Khojah, AA and Ahmad, S and Zaki, MEA},
title = {Quality by Design-Guided Transethosomal Gel of Donepezil Hydrochloride and Quercetin for Potential Alzheimer's Management: Stability-Indicating Eco-Compatible RP-HPLC Method.},
journal = {Drug development research},
volume = {87},
number = {6},
pages = {e70371},
doi = {10.1002/ddr.70371},
pmid = {42635075},
issn = {1098-2299},
mesh = {*Donepezil/chemistry/administration & dosage ; Chromatography, High Pressure Liquid/methods ; *Quercetin/chemistry/administration & dosage ; Gels ; *Alzheimer Disease/drug therapy ; Drug Stability ; *Cholinesterase Inhibitors/chemistry/administration & dosage ; Chromatography, Reverse-Phase ; *Antioxidants/chemistry/administration & dosage ; },
abstract = {Alzheimer's disease requires innovative therapeutic strategies that not only alleviate symptoms but also protect neurons. Donepezil hydrochloride, a cholinesterase inhibitor, and quercetin, a potent antioxidant, were co-formulated into a transethosomal gel to enhance brain delivery and therapeutic efficacy. To design and optimize a Quality by Design (QbD)-based transethosomal gel containing Donepezil hydrochloride and Quercetin, and to establish a stability-indicating, eco-compatible RP-HPLC method for their simultaneous estimation. Chromatographic separation was achieved on a C18 ODS column using an eco-friendly mobile phase of acetonitrile-phosphate buffer (45:55, pH 3.4). Detection was performed at 240 nm, the isoabsorptive wavelength for both drugs. Method validation followed ICH guidelines, and forced degradation studies (acidic, basic, oxidative, thermal, photolytic) were conducted to achieve controlled degradation (5%-20%) while minimizing the use of hazardous solvents. The transethosomal gel was developed using QbD algorithms, optimizing critical parameters including particle size distribution (PDI), zeta potential, entrapment efficiency, and drug release profile. The optimized gel exhibited a vesicle size of 128.4 ± 2.1 nm, PDI of 0.135, zeta potential of +29.52 mV, and 89% and 85% entrapment efficiency of Quercetin and Donepezil HCl. Drug content exceeded 97% for both drugs, while cumulative drug release reached approximately 85%-95% over 10 h. The RP-HPLC method demonstrated excellent linearity (R[2] > 0.995), recovery (98-102%), precision (%RSD < 2%), accuracy, robustness, and an Eco-Scale score of 83.18, confirming excellent analytical greeness. Forced degradation studies confirmed its stability-indicating capability. The study successfully integrates QbD-driven formulation design with a validated eco-friendly RP-HPLC method, providing a robust platform for simultaneous drug delivery in Alzheimer's therapy. This work underscores the synergistic potential of advanced formulation strategies and sustainable analytical validation in translational pharmaceutical research.},
}

*Donepezil/chemistry/administration & dosage
Chromatography, High Pressure Liquid/methods
*Quercetin/chemistry/administration & dosage
Gels
*Alzheimer Disease/drug therapy
Drug Stability
*Cholinesterase Inhibitors/chemistry/administration & dosage
Chromatography, Reverse-Phase
*Antioxidants/chemistry/administration & dosage

@article {pmid42635110,
year = {2026},
author = {Nordbeck, AJ and Martá-Ariza, M and Ek Olofsson, H and Kanshin, E and Ueberheide, B and Jones, K and Sanford, B and Hamlett, ED and Head, E and Mufson, EJ and Perez, SE and Wisniewski, T and Guzman, S and Granholm, AC},
title = {Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71776},
doi = {10.1002/alz.71776},
pmid = {42635110},
issn = {1552-5279},
support = {R01AG071228/AG/NIA NIH HHS/United States ; R01AG0701531//NIH/ ; R01AG081356-01A11/AG/NIA NIH HHS/United States ; U24AG092191-01/AG/NIA NIH HHS/United States ; R01AG061566//NIH/ ; RO1AG081286/AG/NIA NIH HHS/United States ; P30AG066512/AG/NIA NIH HHS/United States ; R01AG087280/AG/NIA NIH HHS/United States ; PO1AG014449./AG/NIA NIH HHS/United States ; CA2018010//BrightFocus Foundation/ ; GRT-2023b/2277//Lejeune Foundation/ ; //Tegger Foundation/ ; //Elly Berggren Foundation/ ; },
mesh = {*Down Syndrome/pathology/metabolism/complications ; *TOR Serine-Threonine Kinases/metabolism ; *Alzheimer Disease/pathology/metabolism/complications ; *Hippocampus/metabolism/pathology ; Humans ; *Insulin/metabolism ; *Signal Transduction/physiology ; Female ; Proteomics ; Male ; },
abstract = {INTRODUCTION: Down syndrome (DS) is caused by a complete or partial trisomy of chromosome 21, resulting in variable intellectual disabilities and a high risk for early-onset Alzheimer's disease (DS-AD). Dysregulation of the mammalian target of rapamycin (mTOR) and insulin (INS) signaling pathways has been reported in DS. We hypothesized that upstream alterations in these two pathways contribute to hippocampal dysfunction in DS-AD.

METHODS: We used spatial transcriptomics and localized proteomic techniques to examine mTOR/INS signaling pathways in subregions of the hippocampus in post mortem tissue from individuals with DS-AD and age-matched neurotypical controls.

RESULTS: mTOR pathways were significantly altered in specific hippocampal subfields in DS-AD, and INS pathways were significantly altered in dentate granule neurons.

DISCUSSION: These preliminary spatial transcriptomics and localized proteomics findings demonstrate an interplay between select hippocampal mTOR/INS pathways and cellular populations, suggesting potential novel drug targets and early biomarkers for DS.},
}

*Down Syndrome/pathology/metabolism/complications
*TOR Serine-Threonine Kinases/metabolism
*Alzheimer Disease/pathology/metabolism/complications
*Hippocampus/metabolism/pathology
Humans
*Insulin/metabolism
*Signal Transduction/physiology
Female
Proteomics
Male

@article {pmid42631247,
year = {2026},
author = {Chen, X and Boey, J and Wei, K and Ding, C and Malagón, P and Hong, JP and Zhou, Z},
title = {The Use of Dynamic Neck Lymphaticovenous Anastomosis in the Adjunctive Treatment of Alzheimer's Disease: A Retrospective Case Series.},
journal = {Archives of plastic surgery},
volume = {53},
number = {4},
pages = {352-360},
pmid = {42631247},
issn = {2234-6163},
abstract = {BACKGROUND: Lymphovenous anastomosis (LVA) has recently emerged as a potential method for the symptomatic management of Alzheimer's disease (AD). Building on this, we conceptualize the "dynamic neck lymphovenous anastomosis" (DN-LVA) to illustrate the versatility of our technique. DN-LVA utilizes a vein graft that traverses through the sternocleidomastoid muscle to facilitate the drainage of lymphatic fluid from the deep cervical lymphatic vessels to the external jugular vein.

METHODS: This study presents a retrospective analysis of patients who underwent DN-LVA between November 2024 and January 2025. The clinical outcome was evaluated through positron emission tomography/computed tomography (PET/CT) imaging and cognitive assessment tools, which included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Clinical Dementia Rating (CDR). The vein graft was harvested from the lower limb.

RESULTS: Five subjects were recruited into this study. Postoperative PET/CT scans revealed up to a 6.9% increase in glucose metabolism in patient 3, a decrease of 12.3% in amyloid deposits, and a 4.7% reduction in tau deposits in patient 5 and patient 4, respectively. Clinically, MMSE and MoCA scores were improved by 1.8 and 1.4, respectively. NPI scores decreased by 5.8 across five overall, and the CDR remained unchanged in all subjects. All grafts demonstrated vessel patency, and no postoperative complications were observed.

CONCLUSION: DN-LVA appears to be a safe, minimally invasive procedure with potential cognitive and metabolic benefits in AD. Further studies with larger cohorts and longer follow-up are warranted to confirm these preliminary findings.},
}

@article {pmid42631306,
year = {2026},
author = {de Oliveira, GLDS and Bertollo, AG},
title = {Non-pharmacological strategies for the management of Alzheimer's disease.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250290},
pmid = {42631306},
issn = {1980-5764},
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disease affecting various cognitive domains, requiring a holistic and integrated therapeutic approach. The treatment of AD goes beyond pharmacological interventions, also necessitating non-pharmacological therapies that can act synergistically, both with each other and with emerging pharmacological treatments, including new anti-amyloid therapies. These therapies aim to improve patients' quality of life and alleviate behavioral symptoms, such as agitation and depression, and delay disease progression. Current clinical and meta-analytic evidence suggests that these approaches can be effectively integrated with conventional treatment, offering a valuable alternative to enhance patients' overall well-being. However, further research is needed to deepen the understanding of the ideal combination of the new anti-amyloid therapies, to address the limitations of current evidence, and to robustly establish their effectiveness in the clinical context of AD, aiming to generate a broader and more lasting impact on disease treatment. This narrative review aims to synthesize the evidence on diverse non-pharmacological therapies for managing AD and discuss their practical implications for clinical care.},
}

@article {pmid42631322,
year = {2026},
author = {Marques, PRB and Montenegro, MLV and Ribeiro, MMC},
title = {Othello syndrome as an early manifestation of Alzheimer's disease: an anatomoclinical case study.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250461},
pmid = {42631322},
issn = {1980-5764},
abstract = {Othello syndrome (OS) is characterized by pathological jealousy toward one's spouse, usually marked by delusions of infidelity. We report the first case of OS in Brazil, similar to the case described by Alzheimer in 1906, in a 54-year-old right-handed patient diagnosed with Alzheimer's disease (AD). The diagnostic workup included a clinical history and a positive family history of dementia, the Clinical Dementia Rating (CDR) scale, the Edinburgh Handedness Inventory, and the Mini-Mental State Examination (MMSE). Electroencephalography revealed slow waves predominantly in the bilateral temporo-frontal regions. Cranial computed tomography showed diffuse cortico-subcortical atrophy compatible with the patient's age, as well as bilateral globus pallidus calcifications. Cerebral single-photon emission computed tomography revealed hypoperfusion in the medial frontal and bilateral temporal regions, more pronounced on the left - particularly in the inferomedial portion of the left temporal lobe - along with mild supratentorial ventricular dilatation. Postmortem examination revealed moderate bilateral fronto-temporo-parietal atrophy, and microscopy showed the presence of senile plaques and neurofibrillary tangles. We report an unusual case of OS as the initial clinical manifestation, later diagnosed as AD.},
}

@article {pmid42631411,
year = {2026},
author = {Elwakil, BH and Helal, AM and El-Khatib, M and Abdelnaser, A and Darwish, AA and Shehata, NS and Akl, SH and Moneer, EA and Bakr, BA and El Wakil, A},
title = {Multilayered Silica-Core/Chitosan-Coated Nanostructures Co-Delivering Tamoxifen and Quercetin Mitigate LPS-Associated Neurodegenerative and Alzheimer's Disease-Like Alterations.},
journal = {Journal of biomedical materials research. Part B, Applied biomaterials},
volume = {114},
number = {8},
pages = {e70150},
doi = {10.1002/jbm.b.70150},
pmid = {42631411},
issn = {1552-4981},
support = {PUP-24-8//Pharos University in Alexandria/ ; },
mesh = {Animals ; *Alzheimer Disease/drug therapy/metabolism/pathology/chemically induced ; *Chitosan/chemistry/pharmacology ; *Quercetin/pharmacology/chemistry/pharmacokinetics ; *Lipopolysaccharides/toxicity ; *Silicon Dioxide/chemistry/pharmacology ; *Tamoxifen/pharmacology/chemistry/pharmacokinetics ; Rats ; Mice ; Male ; },
abstract = {Cholinergic dysfunction, oxidative stress, neuroinflammation, and proteinopathies are among the major hallmarks of Alzheimer's disease (AD). This study aimed to develop and evaluate the therapeutic potential of multilayered silica-based/chitosan-coated nanoparticles (Si@CsNPs) co-loaded with quercetin (QUR) and tamoxifen (TAM) in an LPS-induced neuroinflammatory murine model exhibiting AD-like neuropathological alterations associated with bacterial endotoxin exposure. Molecular docking and target prediction analyses suggested that TAM may exert partial cholinesterase inhibitory activity and potentially interact with muscarinic receptor- and epidermal growth factor receptor (EGFR)-associated pathways, which are implicated in neuroinflammation and oxidative stress regulation. The resulting silica-based/chitosan-coated nanoparticles (Si@CsNPs) co-loaded with QUR and TAM (QUR/TAM-Si@CsNPs) were spherical in shape, exhibited a core-shell architecture, and demonstrated high loading efficiencies for QUR (93.1% ± 2.56) and TAM (84.27 ± 3.66), with a mean particle diameter of approximately 135 nm as determined by TEM. Behavioral assessment using Morris Water Maze revealed that lipopolysaccharide (LPS) administration impaired spatial learning and memory in rats; these effects were significantly ameliorated by QUR/TAM-Si@CsNPs treatment, to a greater extent than Si@CsNPs loaded individually with QUR or TAM. Biochemical, apoptotic, and histopathological analyses further demonstrated that treatment with QUR/TAM-Si@CsNPs normalized acetylcholinesterase activity, Tau protein level, β-amyloid accumulation, pro-inflammatory mediators, and apoptotic indices while preserving hippocampal architecture. Collectively, these findings demonstrate that QUR/TAM-Si@CsNPs exert combined anti-inflammatory and neuroprotective effects, highlighting their promise as a multifunctional nanotherapeutic strategy against LPS-associated neurodegenerative and AD-like neuropathological alterations.},
}

Animals
*Alzheimer Disease/drug therapy/metabolism/pathology/chemically induced
*Chitosan/chemistry/pharmacology
*Quercetin/pharmacology/chemistry/pharmacokinetics
*Lipopolysaccharides/toxicity
*Silicon Dioxide/chemistry/pharmacology
*Tamoxifen/pharmacology/chemistry/pharmacokinetics
Rats
Mice
Male

@article {pmid42631497,
year = {2026},
author = {Gopal, RK and Pathoor, NN and Ganesh, PS},
title = {Eubiosis and dysbiosis in periodontitis-related systemic diseases.},
journal = {Journal of periodontology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jper.70188},
pmid = {42631497},
issn = {1943-3670},
abstract = {BACKGROUND: This narrative review examines the eubiosis-dysbiosis spectrum in periodontitis and its systemic implications. Evidence is drawn from the literature through 2026; as a narrative review, some selection bias cannot be excluded. Periodontitis, affecting 10%-15% of adults globally, drives systemic health disorders through microbial dysbiosis.

OBJECTIVES: This narrative review examines microbial ecological shifts in periodontitis and their implications for cardiovascular disease (CVD), diabetes mellitus (T2D), neurodegenerative disorders, rheumatoid arthritis (RA), and other systemic conditions.

METHODS: We have synthesized the current evidence on oral microbiome transitions from eubiosis to dysbiosis, focusing on mechanistic pathways linking periodontal disease to systemic health outcomes.

RESULTS: Periodontal dysbiosis may influence systemic health through mechanisms including bacteremia, chronic inflammation, molecular mimicry, and microbiome axis interactions. Individuals with periodontitis show 1.5 to 2-fold increased cardiovascular risk, bidirectional relationships with diabetes (HbA1c reductions of 0.3%-0.5% following periodontal treatment), and associations with Alzheimer's disease, rheumatoid arthritis, and inflammatory bowel disease. Key pathogens including Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum have been proposed as keystone species capable of remodeling microbial communities and potentially contributing to systemic effects.

CONCLUSIONS: Understanding the eubiosis-dysbiosis spectrum provides crucial insights into oral-systemic health connections and offers therapeutic targets for managing both periodontal and systemic diseases. Integrated medical-dental care approaches, precision medicine strategies, and microbiome-based therapeutics represent promising future directions.},
}

@article {pmid42631651,
year = {2026},
author = {Chen, KS and Loi, KJ and McGinley, LM and Kashlan, ON and Rigan, DM and Mason, SN and Kwentus, JF and Carter, AD and Savelieff, MG and Feldman, EL},
title = {Human Stem Cell Transplantation, Immunosuppression, and Noninvasive In vivo Cell Tracking in the Mouse Brain.},
journal = {Current protocols},
volume = {6},
number = {8},
pages = {e70442},
pmid = {42631651},
issn = {2691-1299},
support = {U01AG057562//U.S. National Institute on Aging/ ; 1K08AG084902//U.S. National Institute on Aging/ ; AACSF-22-970586//Alzheimer's Association Clinician Scientist Fellowship/ ; //Robert E. Nederlander Sr. Program for Alzheimer's Research/ ; //Robert and Katherine Jacobs Environmental Health Initiative/ ; //Andrea and Lawrence A. Wolfe Brain Health Initiative/ ; //Frank L. and Helen Gofrank Foundation Research Program in AD and Brain Health/ ; //Richard and Jane Manoogian Foundation/ ; //Sinai Medical Staff Foundation/ ; //Frances and Kenneth Eisenberg Emerging Scholar Program/ ; //NeuroNetwork for Emerging Therapies/ ; },
mesh = {Animals ; Humans ; Mice ; *Stem Cell Transplantation/methods ; *Cell Tracking/methods ; Neural Stem Cells/transplantation ; *Brain/cytology ; *Immunosuppression Therapy/methods ; Disease Models, Animal ; Alzheimer Disease/therapy ; },
abstract = {Stem cell therapies have emerged as potential therapeutics of interest for many central nervous system diseases, including stroke, epilepsy, neurodegenerative diseases, and traumatic brain injury. Preclinical models are required to evaluate the migration of transplanted stem cells to various areas of the brain, monitor graft survival to improve immunosuppression regimens, and assess stem cell safety and their efficacy on disease outcomes. Understanding all these aspects of stem cells as therapeutics can help optimize parameters for translation to humans. To facilitate this overarching goal, we report a protocol for human stem cell transplantation into mouse fimbria fornix, the outflow white matter tract of the hippocampus, which facilitates stem cell dissemination to regions distant to the injection site. Although our protocol involves injecting human neural stem cells expressing insulin-like growth factor 1 into an Alzheimer's disease mouse model, it can be altered for application to diverse stem cells and cellular therapeutics, secreting various trophic factors, at multiple dosing schemes, and in different central nervous system targets and disorder models. Our approach is robust and highly reproducible, with demonstrated success in improving memory performance in an Alzheimer's disease mouse model and achieving long-term survival of transplanted cells (up to 32 weeks) in immunocompetent mice, facilitating stem cell studies in the context of neuroimmune crosstalk. Our primary protocol involves administering an anti-CD4/anti-CD40L monoclonal antibody cocktail to prevent graft rejection, with bioluminescence imaging to track transplanted stem cells in vivo. We also present an alternate immunosuppression protocol that relies on tacrolimus and mycophenolate mofetil, which is less costly, albeit less effective (especially in the longer term), than the CD4-CD40L antibody regimen. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Human stem cell transplantation into mouse hippocampus, antibody-based immunosuppression, and in vivo tracking by bioluminescence imaging Alternate Protocol: Immunosuppression by tacrolimus and mycophenolate mofetil.},
}

Animals
Humans
Mice
*Stem Cell Transplantation/methods
*Cell Tracking/methods
Neural Stem Cells/transplantation
*Brain/cytology
*Immunosuppression Therapy/methods
Disease Models, Animal
Alzheimer Disease/therapy

@article {pmid42631698,
year = {2026},
author = {Zhao, T and Wang, TY and Wang, HS and Lim, YJ and Zhang, ZJ and Duan, XR and Li, L and Li, YM},
title = {Tau-Targeted PROTACs Degrade Pathology-Associated Tau and Improve Memory in Alzheimer's Disease Models.},
journal = {ACS chemical biology},
volume = {21},
number = {8},
pages = {1906-1916},
doi = {10.1021/acschembio.6c00096},
pmid = {42631698},
issn = {1554-8937},
support = {22237003//National Natural Science Foundation of China/ ; 92353302//National Natural Science Foundation of China/ ; ZR2022LSW014//Natural Science Foundation of Shandong Province/ ; },
mesh = {*tau Proteins/metabolism ; Animals ; *Alzheimer Disease/drug therapy/metabolism/pathology ; Proteolysis Targeting Chimera ; Mice ; Humans ; Disease Models, Animal ; *Memory/drug effects ; Proteolysis/drug effects ; Mice, Transgenic ; Methylene Blue/chemistry/pharmacology ; },
abstract = {Tau aggregation and hyperphosphorylation are key pathological features of Alzheimer's disease (AD). Because Tau is intrinsically disordered, conventional small-molecule inhibitors have achieved limited success. Proteolysis-targeting chimeras (PROTACs) enable the targeted proteasomal degradation of previously considered undruggable proteins. We designed Tau-targeted PROTAC candidates using methylene blue (MB) as a recognition moiety for aggregation-prone motifs within the microtubule-binding region and varied the linker lengths and E3 ligase recruitment ligands to optimize degradation efficiency. Cell-based screening revealed that MB-2-VHL1 and MB-2-VHL2 are active degraders. In vivo studies confirmed a reduction in total Tau levels and degradation of phosphorylated Tau (p-Tau). In 3xTg-AD mice, subcutaneous administration of MB-2-VHL2 was associated with reduced hippocampal Tau and p-Tau levels and improved recognition memory and spatial learning. MB-2-VHL2 was also detectable in both serum and brain tissue by LC-MS/MS after subcutaneous administration and did not cause detectable histological or biochemical toxicity. These results indicate that MB-2-VHL2 can reduce both total Tau and p-Tau levels in vivo. Although the reduction in p-Tau appeared more pronounced under our experimental conditions, whether MB-2-VHL2 preferentially targets pathological Tau remains to be determined. Overall, these findings support further optimization and preclinical evaluation of Tau-targeted PROTACs as a potential therapeutic strategy for AD.},
}

*tau Proteins/metabolism
Animals
*Alzheimer Disease/drug therapy/metabolism/pathology
Proteolysis Targeting Chimera
Mice
Humans
Disease Models, Animal
*Memory/drug effects
Proteolysis/drug effects
Mice, Transgenic
Methylene Blue/chemistry/pharmacology

@article {pmid42631717,
year = {2026},
author = {Zhang, P and Huang, D and Lu, X and Zhong, H and Liu, C and Liu, H and Duan, X and Wu, J},
title = {Diagnostic value of blood p-tau subtypes in Alzheimer's disease progression and pathology: systematic review and meta-analysis.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42631717},
issn = {1433-8491},
support = {2022-1501//Research Programs of Sichuan Provincial Cadre Healthcare Commission/ ; },
abstract = {BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and the most likely to lead to dementia. With the availability of the latest therapies, the need for Alzheimer's disease diagnosis is now gradually increasing. Whereas blood phosphorylated-tau (p-tau) has demonstrated excellent performance in the prediction and diagnosis of disease progression and Aβ positivity in AD, there are differences between different p-tau subtypes. Therefore, a pooled analysis of different blood p-tau subtypes is of more important clinical value.

METHOD: Relevant literature was screened by complete search in four databases, Pubmed, Embase, Cochrane Library and Scopus. Relevant data and AUC and their confidence intervals of the included literature were extracted and analyzed by classification according to p-tau subtypes. Quality assessment was performed using the QUADAS-2 tool.

RESULT: Our results reveal that p-tau217 performs better in the diagnostic performance in most stages of AD, which is consistent with the guidelines. However, our results concluded that p-tau217 has poorer diagnostic performance in the stages of cognitive unimpaired or less cognitively impaired, especially in the Aβ positivity diagnosis of SCD and CU. Head-to-head meta-analyses formally confirmed that p-tau217 significantly outperforms p-tau181 across AD dementia, Aβ positivity, tau positivity, and biological staging (all P < 0.05), whereas no significant difference was observed between p-tau231 and p-tau181.

CONCLUSION: By integrating single-arm pooled AUC estimates with formal head-to-head statistical comparisons, our study provides evidence-based support for plasma p-tau217 as the subtype with the most robust diagnostic performance across AD pathology and biological staging. Head-to-head analyses formally confirmed that p-tau217 significantly outperforms p-tau181 in Aβ positivity, Tau positivity, and biological staging.},
}

@article {pmid42631776,
year = {2026},
author = {Dineshbhai, TK and Rafaliya, D and Singh, A and Maheshwari, S and Lalan, M and Chakraborthy, GS},
title = {Emerging diagnostic biomarkers and therapeutic targets in Alzheimer's disease.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42631776},
issn = {1568-5608},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common cause of dementia in the world. Cognitive decline, memory problems, behavioral disturbances, and, finally, loss of functional independence characterize it. AD has risen and continues to increase globally, especially among aging people. A team of researchers at the University of Alberta says that we need faster, better diagnosis and treatment of AD. It elaborates on the progressive understanding of AD pathophysiology, biomarkers, emergent targets, and the latest delivery solution. The paper covers and discusses various disease-causing mechanisms like plaque formation, tau hyperphosphorylation, etc., which causes AD. Research is also being undertaken on the role of genetic and epigenetic factors in the pathogenesis and evolution of diseases, including but not limited to APOE polymorphisms, DNA methylation, modifications of histones, and non-coding RNAs. Researchers have discovered biomarkers relevant to AD, particularly those found in CSF and blood. The biomarkers include Aβ42, phosphorylated tau, neurofilament light chain, GFAP, and TREM2. Other biomarkers include salivary, urinary, neuroimaging, and digital. Next come the therapeutic strategies targeting amyloid aggregation, tau pathology, and other types of dysfunctions. Recent developments in monoclonal antibodies, kinase inhibitors, anti-inflammatory agents, neurotrophic agents, and antioxidant therapies are stressed. Moreover, nanotechnology-based and targeted delivery systems being developed for drugs include, but are not limited to, liposomes, polymeric nanoparticles, dendrimers, nanoemulsions, and intranasal formulations to enhance blood-brain barrier permeability. A combination of biomarker-guided diagnostics with mechanism-based therapies might enable precision medicine approaches and improve clinical outcomes in AD.},
}

@article {pmid42631802,
year = {2026},
author = {Grasso, M and Maggio, V and Caraci, F and Rizzo, M},
title = {Glucose-Lowering Therapies and Cognitive Decline: From Molecular Mechanisms to Clinical Evidence and Future Perspectives.},
journal = {Advances in therapy},
volume = {},
number = {},
pages = {},
pmid = {42631802},
issn = {1865-8652},
abstract = {Several lines of evidence suggest the relationship between diabetes and cognitive decline. Patients with a diagnosis of type 2 diabetes (T2D) present an increased risk of Alzheimer's disease (AD) development than the general population, and it is known that brain insulin resistance (IR) plays a key role in the conversion from mild cognitive impairment (MCI) into AD. During recent years, emerging therapeutic perspectives have been proposed with the aim of targeting T2D-related cognitive impairment, and glucose-lowering drug classes, especially glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter inhibitors (SGLT2is), demonstrated neuroprotective effects and a positive effects on cognitive function acting by several molecular mechanisms including anti-inflammatory activity, modulation of insulin signaling, and promoting the neurogenesis process. Different clinical trials showed their ability in preventing neurodegenerative decline, with numerous phase II and III trials underway in populations with AD; however, although preclinical evidence is promising and some clinical data are encouraging, translating these results into established therapeutic strategies requires larger, randomized, and controlled clinical trials with extended follow-up period, standardized cognitive assessments, and inclusion of molecular and imaging biomarkers. Addressing these gaps will be essential to determine whether glucose-lowering drug classes can be introduced into clinical practice to prevent or slow cognitive decline in patients with T2D, exerting neuroprotective activity beyond their effect on glycemic control.},
}

@article {pmid42632150,
year = {2026},
author = {Chenxi, D and Miaomiao, W and Jiahui, F and Hongming, Z and Lu, G and Lihua, W and Ying, Z and Xiaoqing, C and Jing, Z and Yanhong, S},
title = {Technological evolution of hyperthermia: From traditional moxibustion to nanomaterial-mediated platforms for inflammatory diseases.},
journal = {Journal of thermal biology},
volume = {140},
number = {},
pages = {104557},
doi = {10.1016/j.jtherbio.2026.104557},
pmid = {42632150},
issn = {0306-4565},
abstract = {Hyperthermia, a physical therapeutic modality with unique advantages in treating inflammatory diseases, has evolved rapidly from empirical practice to precision medicine. Technologically, it has expanded from whole-body hyperthermia and traditional moxibustion to localized approaches, including photothermal, magnetothermal, ultrasound, and implantable platforms. Traditional moxibustion acts through heat and near-infrared radiation, while nanomaterials and smart devices now enable precise control over temperature, spatial targeting, and treatment duration. these modalities converge on conserved mechanisms: TRPV channel activation, HSF1-HSP70 induction, and immune modulation, which collectively alleviate inflammation and promote tissue repair in inflammatory bowel disease, osteoarthritis, and Alzheimer's disease. This review summarizes technological evolution, mechanistic insights and therapeutic applications, thereby providing a framework for developing precision hyperthermia strategies and multifunctional platforms for inflammatory diseases.},
}

@article {pmid42627514,
year = {2026},
author = {Cao, Q and Shen, M and Liu, Y and Li, C and Liu, L and Zhou, J and Yue, R and Niu, D and Ren, Y and Pan, L and Yao, J and Zhang, G},
title = {The role of microglia glucose metabolism reprogramming in Alzheimer's disease treatment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261478594},
doi = {10.1177/13872877261478594},
pmid = {42627514},
issn = {1875-8908},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment, and there remains a lack of effective treatments capable of reversing or significantly slowing disease progression. Accumulating evidence indicates that the immune function of microglia, the resident immune cells of the central nervous system, is a critical factor in regulating AD pathogenesis. Emerging research in immunometabolism further reveals that glucose metabolic reprogramming serves as a central driver of microglial phenotypic and functional differentiation. This review systematically outlines the fundamental characteristics of microglial glucose metabolism and focuses on how the dynamic metabolic reprogramming it undergoes during AD progression regulates microglial immune behavior and inflammatory responses. Building on this, we further summarize key regulatory targets within the "metabolism-immune axis" and corresponding pharmacological intervention strategies. Finally, this article discusses current challenges and future research directions in the field of microglial immunometabolism. This review aims to provide a theoretical foundation for AD intervention strategies targeting the "metabolism-immune axis" and to offer insights for the development of novel disease-modifying therapeutics.},
}

@article {pmid42627571,
year = {2026},
author = {Wang, Q and Wei, Y and Shen, C and Kang, W and Wang, L},
title = {CT1812 Attenuates Surgery-Induced Cognitive Impairment and Modulates TMEM97- and PGRMC1-Associated Hippocampal Stress Responses in Aged Mice.},
journal = {Neurochemical research},
volume = {51},
number = {5},
pages = {},
pmid = {42627571},
issn = {1573-6903},
support = {82201549//National Natural Science Foundation of China/ ; },
mesh = {Animals ; *Membrane Proteins/metabolism ; *Hippocampus/drug effects/metabolism ; Male ; Mice, Inbred C57BL ; Mice ; *Aging/drug effects/metabolism ; *Cognitive Dysfunction/metabolism/drug therapy/etiology ; *Postoperative Cognitive Complications/metabolism/drug therapy ; Receptors, Progesterone ; },
abstract = {Postoperative neurocognitive disorders (PND) are common complications in older surgical patients, but druggable mechanisms linking surgical trauma to hippocampal synaptic and cognitive vulnerability remain poorly defined. The σ-2 receptor (σ-2R), encoded by transmembrane protein 97 (TMEM97), and progesterone receptor membrane component 1 (PGRMC1) intersect membrane lipid biology and synaptic stress signaling; CT1812, a pharmacological σ-2R complex modulator, has shown target engagement in early Alzheimer's disease trials, but whether this pathway participates in postoperative hippocampal injury is unknown. This study examined whether surgery-induced hippocampal stress in aged mice is associated with TMEM97 and PGRMC1 signaling and whether early CT1812 treatment can attenuate this response. Young adult (2-3 months) and aged (18-20 months) male C57BL/6J mice underwent sham operation or laparotomy; aged mice were further treated with vehicle or CT1812 (3 mg/kg, intravenous injection, days 0-3). Hippocampal molecular changes were assessed by western blotting and immunofluorescence on day 3, and behavior was evaluated by open field test (OFT) and Morris water maze (MWM) on days 6-10. Laparotomy increased hippocampal TMEM97 and PGRMC1 expression and induced anxiety-like and spatial-memory deficits preferentially in aged mice, without evidence that locomotor impairment explained the behavioral phenotype. TMEM97 and PGRMC1 were detected in neuronal nuclei (NeuN)-positive neurons, ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia, and glial fibrillary acidic protein (GFAP)-positive astrocytes in hippocampal cornu ammonis 1 (CA1), supporting multicellular pathway involvement. In aged surgical mice, CT1812 significantly reduced upregulation of TMEM97 and PGRMC1, improved OFT center-zone occupancy and MWM performance, and restored the synaptic markers postsynaptic density protein 95 (PSD95) and synaptophysin. CT1812 also normalized lipid-handling proteins, including apolipoprotein E (ApoE), ATP-binding cassette transporter A1 (ABCA1), cholesterol 24-hydroxylase (CYP46A1), and low-density lipoprotein receptor (LDLR), and reduced perilipin 2 (PLIN2) accumulation in neurons and microglia. In parallel, CT1812 attenuated a selective endoplasmic reticulum (ER) stress response involving binding immunoglobulin protein (BIP) and protein kinase R-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) signaling in hippocampal neurons, and suppressed microglial nuclear factor κB (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammatory activation, whereas C/EBP homologous protein (CHOP) was not significantly changed. These findings support a model in which postoperative injury in the aged hippocampus engages a lipid-proteostatic and inflammatory stress program associated with TMEM97 and PGRMC1, and suggest that CT1812 attenuates cognitive vulnerability by restraining this coupled response.},
}

Animals
*Membrane Proteins/metabolism
*Hippocampus/drug effects/metabolism
Male
Mice, Inbred C57BL
Mice
*Aging/drug effects/metabolism
*Cognitive Dysfunction/metabolism/drug therapy/etiology
*Postoperative Cognitive Complications/metabolism/drug therapy
Receptors, Progesterone

@article {pmid42627617,
year = {2026},
author = {Fawzy, MN},
title = {The neuroimmune network in Alzheimer's and Parkinson's diseases: from mechanistic insights to biomarker-guided immunotherapies and clinical translation.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {42627617},
issn = {1568-5608},
abstract = {Neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) have traditionally been examined from the perspectives of neurons or microglia, resulting in constrained therapeutic achievements. Recent findings endorse a cohesive neuroimmune framework in which central nervous system (CNS)-resident microglia, border-associated macrophages, clonally proliferated CD8[+] T cells, and peripheral signaling centers (IL-20 family, gut-brain axis) perpetuate chronic maladaptive inflammation via feed-forward mechanisms. This review critically examines investigational immunotherapies aimed at this network: the CNS‑penetrant NLRP3 inhibitor NT-0796 (Phase 1b/2a) demonstrated preliminary biomarker reductions in axonal damage and T-cell activation in PD but remains unapproved and necessitates further confirmatory trials; the anti‑SIGLEC10 antibody ONC-841 improved microglial phagocytosis of Aβ and tau in preclinical studies but has yet to commence human trials; and CAR‑based platforms (CAR-T/NK) remain in the nascent preclinical phase, facing significant delivery and toxicity challenges. A three-part biomarker framework, encompassing target engagement (CSF IL-1β, caspase-1), pharmacodynamic responses (neurofilament light chain, ASC specks), and predictive endotyping (T-cell clonality, complement profiles), is proposed to facilitate patient stratification by neuroimmune endotype. None of these agents have received regulatory approval for neurodegenerative conditions; all findings are preliminary. Effective immunotherapy may ultimately necessitate multi-node, network-aware combinations (e.g., inflammasome inhibition coupled with Treg augmentation) rather than single-target suppression. Embracing this complexity offers a roadmap for future disease-modifying therapies, though rigorous clinical validation remains essential.},
}

@article {pmid42627656,
year = {2026},
author = {Meiselbach, MK and Xu, J and Brown, T and Polsky, D},
title = {Medicare Advantage Beneficiary Enrollment Decisions Following New Complex Conditions.},
journal = {JAMA health forum},
volume = {7},
number = {8},
pages = {e262843},
doi = {10.1001/jamahealthforum.2026.2843},
pmid = {42627656},
issn = {2689-0186},
mesh = {Humans ; *Medicare Part C/statistics & numerical data ; United States ; Female ; Male ; Aged ; Chronic Disease/epidemiology ; Aged, 80 and over ; Cohort Studies ; Insurance, Medigap/statistics & numerical data ; },
abstract = {IMPORTANCE: Prior research has demonstrated higher rates of disenrollment from Medicare Advantage (MA) among people with greater health care needs. Yet, less is known about how disenrollment responds to changes in medical complexity, whether disenrollment varies by the degree of complexity, and how these patterns differ by state Medigap protections and MA plan characteristics.

OBJECTIVE: To examine changes in MA plan disenrollment following the development of new complex medical conditions and assess heterogeneity by number of conditions, state Medigap policy, and plan characteristics.

This cohort study used Medicare enrollment and claims data from 2016 to 2021. The study population included beneficiaries continuously enrolled in MA in 2016 without complex medical conditions from 2016 through 2018. A treatment group developed a new complex condition in 2019; a comparison group did not develop a complex condition through 2021. Data were analyzed from December 1, 2025, to March 1, 2026.

EXPOSURE: Development of 1 or more new complex medical conditions in 2019, including acute myocardial infarction, Alzheimer disease and related dementia, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, depression, congestive heart failure, or stroke.

MAIN OUTCOMES AND MEASURES: Annual disenrollment from the prior year MA plan, which included disenrollment to traditional Medicare (TM) or switching to another plan within MA. Difference-in-differences models with beneficiary and year fixed effects were estimated and converted to differences in percentage points.

RESULTS: The analytic sample included 1 054 926 beneficiaries, including 219 942 (mean [SD] age, 75.3 [6.3] years; 54.6% female) who developed new complex conditions in 2019 and 834 984 (mean [SD] age, 73.8 [5.6] years; 56.7% female) who did not develop a new complex condition in 2019. Developing any new complex condition was associated with an increase of 3.3 (95% CI, 3.1-3.5) percentage points (pp) in MA disenrollment, including an increase of 2.8 (95% CI, 2.7-2.9) pp in disenrollment to TM. The number of new complex conditions was associated with increased disenrollment, from 1.4 (95% CI, 1.3-1.6) pp for 1 condition to 12.8 (95% CI, 11.6-13.9) pp for 4 or more conditions. Disenrollment to TM was 1.5 (95% CI, 0.9-2.1) pp higher among beneficiaries residing in states with Medigap guaranteed issue and community rating protections.

CONCLUSIONS AND RELEVANCE: In this study, development of new complex medical conditions was associated with higher MA disenrollment, particularly to TM and in states with Medigap protections, and the magnitude increased with medical complexity. These findings highlight how changes in health status and state policy may shape Medicare coverage decisions.},
}

Humans
*Medicare Part C/statistics & numerical data
United States
Female
Male
Aged
Chronic Disease/epidemiology
Aged, 80 and over
Cohort Studies
Insurance, Medigap/statistics & numerical data

@article {pmid42627738,
year = {2026},
author = {Chang, Y and Kim, HJ and Kim, Y and Park, A and Nam, S and Banerjee, DR and Hasenour, CM and Young, JD and Brooks, GA and Wolfe, RR and Kim, IY},
title = {Exogenous lactate ameliorates Aβ-induced energy deficit and neurotoxicity with increased mitochondrial TCA cycle carbon flux in SH-SY5Y cells.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00268.2026},
pmid = {42627738},
issn = {1522-1563},
support = {2021R1A2C3005801//National Research Foundation of Korea (NRF)/ ; GCU-202106260001//Gachon University/ ; //Myocare Inc/ ; },
abstract = {A growing body of evidence has demonstrated the existence of metabolic dysfunction in neurodegenerative diseases, including Alzheimer's disease (AD), suggesting that deprivation of energy substrates impairs cellular dynamics. As the glucose utilization declines in AD patients, the need for alternative energy sources becomes crucial to sustain neuronal activities and prevent cell death induced by neurotoxic proteins, such as amyloid beta (A(?)) aggregates. In this context, lactate has been investigated as a potential alternative brain energy substrate in several studies, yet its impact on neuronal cells under A(?)-induced toxicity remains unclear. We confirmed significant suppression of energy production-related biological pathways by analyzing brain transcriptomic data of AD patients. In subsequent in vitro studies, exogenous lactate treatment ameliorated neuron-like cell death caused by A(?) aggregates. Using a [13]C stable isotope tracer, we verified cellular lactate uptake and its incorporation into TCA cycle in neurons under the neurotoxic condition. [13]C metabolic flux analysis further supported these findings by revealing that lactate treatment restored Aβ-suppressed mitochondrial TCA cycle fluxes. These metabolic improvements were accompanied by increased expression of mitochondrial proteins. These findings support lactate shuttling as a mechanism for supplying lactate-derived carbon to mitochondrial energy metabolism, which may improve neuronal resilience under Aβ-induced metabolic stress.},
}

@article {pmid42627850,
year = {2026},
author = {Noor, AI and Suha, HN and Hossain, I and Almatarneh, MH and Al-Msiedeen, AM and Bari, MAU and Poirier, RA and Uddin, KM},
title = {Computational insights into the anti-Alzheimer potential of alkynyl-3-carboxamide derivatives.},
journal = {Physical chemistry chemical physics : PCCP},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6cp00485g},
pmid = {42627850},
issn = {1463-9084},
abstract = {Alzheimer's disease (AD) remains a major global health challenge due to its complex pathological mechanisms and the limited availability of effective disease-modifying therapies. In this study, a dataset of fifty novel alkynyl-3-carboxamide derivatives (1-50) was systematically evaluated as potential inhibitors of asparagine endopeptidase (legumain), a key enzyme implicated in AD-associated neurodegeneration. An integrated computational approach involving molecular docking, molecular dynamics (MD) simulations, molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) binding free energy analysis, density functional theory (DFT) calculations, and ADMET profiling was employed to investigate ligand-protein interactions, structural stability, electronic properties, and drug-likeness. Molecular docking analysis across ten disease-relevant protein targets identified ligand 4 as the most promising candidate, showing the highest binding affinity toward legumain (PDB ID: 5LUA) with a docking score of -8.1 kcal mol[-1]. Temperature-dependent MD simulations performed at 300, 305, 310, and 320 K confirmed the stability of the 5LUA-ligand 4 complex, as indicated by consistently low root-mean-square deviation (RMSD) fluctuations and stable binding interactions. MM/PBSA calculations further demonstrated favorable binding thermodynamics for ligand 4, with a total Gibbs free energy of binding (ΔG_bind) of -37.05 kcal mol[-1]. Furthermore, physicochemical and pharmacokinetic assessments revealed favorable drug-like characteristics, including compliance with Lipinski's and Veber's criteria, suitable lipophilicity (c log P = 2.03), topological polar surface area (TPSA = 131.4 Å[2]), and an acceptable predicted hERG inhibition profile (pIC50 = 0.9881) with no significant toxicity alerts. Overall, these computational findings, supported by previously reported in vitro evidence, suggest that ligand 4 represents a promising alkynyl-3-carboxamide-based lead scaffold for further development as a potential legumain-targeted therapeutic candidate for AD. Additional experimental validation through advanced biological assays and in vivo studies is required to confirm its efficacy and safety profile.},
}

@article {pmid42628375,
year = {2026},
author = {Erukulla, R and Reid, G and Yotter, C and Dounavi, ME and Low, A and O'Brien, JT and Ritchie, C and Lawlor, B and Naci, L and Malhotra, P and Koychev, I},
title = {Insulin resistance and brain health in midlife: a potential dementia prevention target.},
journal = {EBioMedicine},
volume = {131},
number = {},
pages = {106448},
doi = {10.1016/j.ebiom.2026.106448},
pmid = {42628375},
issn = {2352-3964},
abstract = {BACKGROUND: Insulin resistance is recognised as a midlife risk factor for cognitive decline, yet the pathways linking metabolic dysfunction to early brain changes remain unclear.

METHODS: We cross-sectionally analysed 355 cognitively normal adults from the PREVENT cohort to test associations between insulin sensitivity (Homoeostatic Model Assessment for Insulin Resistance; HOMA-IR), frontal white matter hyperintensities (WMH), cerebral blood flow (CBF), hippocampal volume, and cognition.

FINDINGS: Multivariable regression showed higher log-transformed HOMA-IR was associated with greater frontal WMH burden (β = 0.118, p = 0.026) and lower global cognitive performance (β = -0.132, p = 0.012). Decreased insulin sensitivity was not associated with global CBF (β = -0.019, p = 0.74). Adjusting for WMH burden, hippocampal volume, and CBF, lower insulin sensitivity remained associated with lower global cognition (β = -0.123, p = 0.021). Structural equation modelling (n = 328) demonstrated a direct negative association between higher HOMA-IR and cognition (β = -0.055, p = 0.042) and trended toward higher vascular burden (p = 0.06). The indirect pathway through vascular burden was non-significant (p = 0.23), as vascular burden, hippocampal volume, and CBF did not associate with cognition.

INTERPRETATION: Decreased insulin sensitivity was linked to early small vessel disease and measurable cognitive differences, suggesting the cognitive association was largely direct rather than explained by vascular injury, hippocampal atrophy, or global perfusion. These findings point toward partially parallel metabolic and vascular pathways rather than a sequential process. These cross-sectional associations suggest that insulin sensitivity warrants investigation as a modifiable midlife factor for cognitive health; interventional studies are needed to determine whether targeting it preserves cognition before neurodegenerative markers emerge.

FUNDING: MRC Dementias Platform UK, NIHR, Alzheimer's Society, Alzheimer's Association, Race Against Dementia, and HRB.},
}

@article {pmid42628381,
year = {2026},
author = {Quan, YS and Liu, JY and Liu, H and Sun, YX and Wang, YL and Liu, Z and Quan, ZS and Shen, QK},
title = {Design synthesis and evaluation of usnic acid derivatives as multi-target drugs for Alzheimer's disease.},
journal = {Bioorganic chemistry},
volume = {181},
number = {},
pages = {110398},
doi = {10.1016/j.bioorg.2026.110398},
pmid = {42628381},
issn = {1090-2120},
abstract = {The pathogenesis of AD is complex, and existing clinical drugs only alleviate symptoms and are difficult to block the course of the disease. Although UA has neuroprotective activities such as antioxidant and anti-inflammatory properties, its anti-AD activity is severely restricted by drug defects such as a single target and insufficient blood-brain barrier permeability. Therefore, this study takes UA as the lead compound, designs and synthesizes 38 UA derivatives, systematically evaluates their anti-AD biological activity, and aims to screen for multifunctional anti AD lead compounds. Among them, the lead compound S12 exhibited exceptional activity, with an EC50 value of 1.24 μM representing a 17.9-fold improvement in potency relative to the parent compound. Furthermore, WB assays were conducted to elucidate the underlying mechanism of action of this compound. The results revealed that compound S12 exerts anti-AD activity through the synergistic modulation of multiple signaling pathways: it inhibits activation of the MAPK and NF-κB pathways, as well as aberrant phosphorylation of tau protein; concurrently, it downregulates BACE1 expression to reduce Aβ production, and suppresses activation of the Bax/Bcl-2 pathway thereby inhibiting caspase-1 activation and ultimately confers neuroprotective, anti-AD effects. The apparent permeability coefficient of compound S12 across an in vitro (BBB) model was determined to be 7.66 × 10[-6] cm/s, confirming its ability to effectively cross the BBB. Further pharmacological evaluation demonstrated that S12 exerted a potent ameliorative effect on learning and memory deficits in an AD mouse model. In vivo toxicity assessment, no gross or histopathological abnormalities were observed in the major organs, including the heart, liver, spleen, and kidneys. Moreover, S12 significantly attenuated neuronal pathological injury in the hippocampus of Aβ-induced AD model mice, underscoring its robust neuroprotective activity. In conclusion, compound S12 demonstrates robust efficacy in ameliorating learning and memory deficits, enhancing blood-brain barrier permeability, and exerting anti-AD activity. Accordingly, it represents a highly promising multifunctional therapeutic candidate for the treatment of AD.},
}

@article {pmid42628699,
year = {2026},
author = {Bergamo, G and Fernandes, M and Maio, S and Albanesi, G and Antonucci, M and Barbaro, I and Cirillo, F and Fernando, L and Amicucci, G and Centonze, D and Liguori, C},
title = {Instrumental, Neurophysiological, cognitive and Sleep InvestiGations into the High risk of neurodegeneraTion in Late Onset Epilepsy of Unknown aetiology: the INSIGHT-LOEU study.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112237},
doi = {10.1016/j.mad.2026.112237},
pmid = {42628699},
issn = {1872-6216},
abstract = {Late-onset epilepsy (LOE) remains of unknown aetiology (LOEU) in around 20% of cases. Longitudinal studies have demonstrated the presence of early cognitive impairment at seizure onset, progressive memory decline and a substantially elevated risk of dementia within a decade of diagnosis, with an increased risk of subsequent neurodegenerative disorders, particularly Alzheimer's disease (AD). LOEU is associated with cognitive network alterations and epileptiform activity, although links remain unclear. Further emerging data suggest that neurodegenerative processes related to β-amyloid and tau pathology may precede the onset of epilepsy. Although epilepsy is highly prevalent among older adults, its impact on quality of life remains unclear, with affective symptoms and sleep disturbances as key determinants of subjective well-being. These findings suggest that LOEU should be reconceptualised as a multidimensional neurological condition. This protocol advocates an integrated approach, combining neuropsychological assessment, advanced biomarkers, neurophysiological measures and systematic sleep evaluation to identify high-risk phenotypes and define optimal windows for neuroprotective interventions in LOEU. This strategy could improve the early detection of cognitive decline, guide personalised management, and ultimately enhance quality of life, while contributing to the long-term sustainability of healthcare systems in an ageing population, focusing on LOEU as a model for dementia prevention.},
}

@article {pmid42628701,
year = {2026},
author = {Wyatt-Johnson, SK and Joshi, S and Blair, M and Desai, JM and Haeryfar, SMM and Lasagna-Reeves, CA and Brutkiewicz, RR},
title = {The MR1/MAIT cell axis has limited effects on the start of tau pathology in a mouse model of tauopathy.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {106969},
doi = {10.1016/j.bbi.2026.106969},
pmid = {42628701},
issn = {1090-2139},
abstract = {Immunity impacts all aspects of Alzheimer's disease (AD) pathology. Previously, we found improved pathology and cognition in the amyloid-focused 5XFAD mouse model deficient in the innate immune cell axis consisting of the innate-like mucosal-associated invariant T (MAIT) cells and the MHC class I-like antigen-presenting molecule they recognize, MR1. However, little is known about how a lack of the MR1/MAIT cell axis impacts cognition and whether an increased abundance of MAIT cells impacts pathology and cognition in the tau-focused PS19 mouse model. We crossed PS19 mice onto an MR1 KO background, resulting in a lack of both MR1 and MAIT cells, and alternatively, onto MAIT[CAST] mice, that have ∼7× more MAIT cells. Using immunofluorescent microscopy, flow cytometry, and cognitive tests including Barnes maze and Novel Object Recognition, we analyzed the impact of MAIT cell numbers on tau pathology. Although an elevation in MAIT cell frequency was found that expressed higher levels of CD69 in PS19 mice on the MAIT[CAST] vs. wildtype background, overall MAIT cell numbers in the brain did not differ between these groups. Interestingly, increased MR1 expression was detected on microglia only in PS19 mice, whereas MR1 was higher in PS19 and PS19/MAIT[CAST] mouse astrocytes. Increased MAIT cell numbers did not alter tau accumulation or cognitive performance, whereas the lack of the MR1/MAIT cell axis did not affect tau burden, but was associated with reduced neuronal density and impaired recognition memory. Together, these findings suggest that the MR1/MAIT cell axis does not substantially influence the early development of tau pathology.},
}

@article {pmid42628773,
year = {2026},
author = {Tani, H},
title = {A replicated astrocyte long non-coding RNA signature of Alzheimer's disease is inverted in amyotrophic lateral sclerosis.},
journal = {Brain research},
volume = {1891},
number = {},
pages = {150513},
doi = {10.1016/j.brainres.2026.150513},
pmid = {42628773},
issn = {1872-6240},
abstract = {Reactive astrocyte transitions are central to neurological disease, yet their long non-coding RNA (lncRNA) regulators remain poorly defined, and single-nucleus studies frequently treat nuclei rather than donors as replicates. This study analyses publicly available human single-nucleus RNA sequencing from four disorders using donors as the unit of inference throughout: Alzheimer's disease (AD; middle temporal gyrus, 88 donors), C9orf72-associated amyotrophic lateral sclerosis and ALS/frontotemporal dementia (ALS; frontal cortex), multiple sclerosis (MS; cortex and white matter), and major depressive disorder (MDD; amygdala). The public MDD release pools nuclei by condition, so that arm cannot support donor-level inference and is exploratory only. Covariate-adjusted pseudobulk analysis of 70,009 CE astrocytes, controlling for sex, age at death and assay chemistry, identified 1,019 down-regulated autosomal lncRNAs after sex-chromosome transcripts were removed. This signature was not attributable to astrocyte subtype composition, which did not differ between groups, and 99.9% of members remained down-regulated within the dominant homeostatic subtype alone. The signature replicated in an independent AD cohort (32 of 41 testable members concordant; resampling P < 0.0001). Testing it outside AD gave a directional result: it was concordant in the MS discovery cohort (P < 0.0001) but inconclusive in an independent MS cohort in which the transcripts lay near the detection floor, and it was reproducibly inverted in ALS, in the C9orf72 discovery cohort and in an independent motor-cortex cohort not restricted to C9orf72 carriers. The inversion survived negative controls for global normalisation and expression level. These astrocyte lncRNA changes are therefore disorder-specific rather than pan-neuroinflammatory.},
}

@article {pmid42628775,
year = {2026},
author = {Marakhovskaya, YA and Churov, AV and Arbatsky, MS and Sergeeva, SP},
title = {Ferroptosis and Alzheimer's disease: Neuroimmune crosstalk and pharmacological opportunities.},
journal = {Brain research},
volume = {},
number = {},
pages = {150514},
doi = {10.1016/j.brainres.2026.150514},
pmid = {42628775},
issn = {1872-6240},
abstract = {Alzheimer's disease (AD) develops through interacting proteinopathic, metabolic, oxidative, and neuroimmune processes. Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and failure of antioxidant defense systems. This review examines the bidirectional interface between ferroptosis and neuroinflammation in AD and distinguishes direct AD-related evidence from findings derived from experimental models and broader ferroptosis or inflammatory studies. Iron dyshomeostasis, impaired ferroportin-dependent iron export, lipid peroxidation, and reduced glutathione/GPX4-dependent protection may increase neuronal susceptibility to ferroptotic injury. In turn, oxidized lipids and danger-associated molecular patterns released from damaged neurons may activate microglia and astrocytes, engage inflammasome and complement signaling, and amplify inflammatory responses. Conversely, cytokine signaling, altered iron handling, and immune-cell redox and lipid remodeling may further increase ferroptotic vulnerability. We also compare ferroptosis-related markers and pathways in neurons, microglia, and astrocytes and discuss potential therapeutic approaches targeting iron metabolism, lipid peroxidation, GPX4 activity, system xc - function, NRF2-related antioxidant defense, neuroimmune signaling, and multitarget compounds. Although available evidence supports an association between ferroptosis-related processes and AD pathobiology, no single marker is sufficient to establish ferroptosis in human AD tissue. This limitation currently restricts the diagnostic and therapeutic interpretation of ferroptosis in AD.},
}

@article {pmid42628844,
year = {2026},
author = {Huang, JW and Wang, YF and Zheng, WH and Cui, QQ and Gao, SQ and Guo, Y},
title = {Viral infection and dementia risk: A systematic bidirectional Mendelian randomization analysis.},
journal = {Virus research},
volume = {},
number = {},
pages = {199794},
doi = {10.1016/j.virusres.2026.199794},
pmid = {42628844},
issn = {1872-7492},
abstract = {BACKGROUND: Viral infections have attracted increasing interest as potentially alterable risk factors for dementia; nonetheless, the results from observational research are variable and prone to confounding bias and reverse causation. This work seeks to systematically explore the potential causal associations between several viral infections and various forms of dementia by a Mendelian randomization methodology utilizing summary statistics and extensive genomic data from the Finnish FinnGen R12 database.

METHODS: This study initially included 14 viral infections, including anogenital herpes, infectious mononucleosis, acute hepatitis B, herpesviral infections, acute poliomyelitis, rubella, varicella, viral warts, herpes zoster, COVID-19, measles, mumps, acute hepatitis A, and HIV infection. The outcome measurements included 15 forms of dementia, including Alzheimer's dementia, vascular dementia and its subtypes, and frontotemporal dementia. The principal analysis utilized the inverse variance weighted (IVW) methodology. This report provides the number of SNPs in each analysis, the mean F statistic, the causal effect estimates, and their 95% confidence ranges. All the MR-Egger regression, weighted median, simple mode, and weighted mode approaches were used in the sensitivity analyses.

RESULTS: The final analysis omitted acute hepatitis A, HIV infection, and measles because of inadequate instrumental variables (only 1-2 SNPs). The IVW primary analysis revealed 6 associations with uncorrected P < 0.05 among the remaining 11 viral infections. Rubella infection was associated with a decreased risk of vascular dementia (subcortical type) (OR = 0.8304; 95% CI: 0.7154-0.9638; P = 0.0145; SNPs = 7; mean F statistic = 25.56) and showed a negative association with the outcome of the composite dementia, including that of Alzheimer's disease (OR = 0.9553; 95% CI: 0.9128-0.9998; P = 0.0488). Viral wart infection was associated with a reduced risk of Alzheimer's dementia (OR = 0.9095; 95% CI: 0.8332-0.9928; P = 0.0338; SNPs = 11; mean F-statistic = 56.01), any dementia (strict exclusion criteria) (OR = 0.9278; 95% CI: 0.8668-0.9932; P = 0.0310), and Parkinson's-related dementia (OR = 0.8182; 95% CI: 0.6796-0.9852; P = 0.0342). There was a suggestive link between mumps infection and a higher risk of vascular dementia (mixed type) (OR = 1.5579; 95% CI: 1.2219-1.9864; P = 0.0003; SNPs = 5; mean F-statistic = 22.63). This link was equally strong in the weighted median analysis (OR = 1.4131, P = 0.0277). In fact, statistically significant connections were not found between any types of viral infections and dementias (after multiple testing correction). Furthermore, for the other viral infections, no associations were observed even at the uncorrected P < 0.05 level. All findings with uncorrected P < 0.05 were successfully tested for heterogeneity and pleiotropy, and sensitivity analyses revealed consistent effect directions.

CONCLUSION: This study offers suggestive genetic evidence for potential associations between certain viral infections and specific forms of dementia. Infections with rubella and viral warts may correlate with a diminished risk of dementia; however, mumps infection may increase the risk of vascular dementia (mixed type). It was not possible to reliably evaluate acute hepatitis A and HIV infection since there were not enough instrumental variables. These results provide preliminary insights into the influence of infectious agents on neurodegenerative disorders, serving as a hypothesis-generating framework for future epidemiological and mechanistic research.},
}

@article {pmid42629112,
year = {2026},
author = {Chen, X and Zhang, X and Chen, C and She, J and Liu, Y and Zhang, C and Cai, J and Tang, L and Zhou, X},
title = {"Marine Rule": discovery of marine natural small molecule drug leads in China in the past decade.},
journal = {Chinese journal of natural medicines},
volume = {24},
number = {9},
pages = {1025-1049},
doi = {10.1016/S1875-5364(26)61202-2},
pmid = {42629112},
issn = {1875-5364},
mesh = {*Drug Discovery ; China ; *Biological Products/chemistry/pharmacology ; *Aquatic Organisms/chemistry ; Humans ; Animals ; Structure-Activity Relationship ; },
abstract = {This review systematically analyzes 186 valid data points derived from 157 distinct marine natural small-molecule drug leads discovered in China in the past decade (2015-2024). These compounds have all undergone phenotypic and target studies, and certain "structure-activity-target" relationships have been established, revealing the recent progress in the basic research of marine drug discovery in China. Therapeutically, antitumor agents dominated (50.0%), while emerging candidates for Alzheimer's disease (3.8%) and osteoporosis (5.4%) demonstrated the multi-target potential of marine chemistry. Ecologically, marine fungi (45.2%) and mangrove symbionts (11.8%) have emerged as prolific sources. Strikingly, 38.2% of the compounds exceeded Lipinski's 500 Da threshold, with higher-molecular-weight agents leveraging macrocyclic architectures (e.g., polyketide-alkaloid hybrids) to enhance bioactivity. These findings challenge traditional drug-likeness criteria and propose a "Marine Rule" framework that prioritizes conformational rigidity, ecosystem-driven scaffold optimization, and the repurposing of defense molecules. This review provides critical insights into China's evolving leadership in marine natural product research and offers strategic guidance for future innovations in the discovery of small molecule leads.},
}

*Drug Discovery
China
*Biological Products/chemistry/pharmacology
*Aquatic Organisms/chemistry
Humans
Animals
Structure-Activity Relationship

@article {pmid42629121,
year = {2026},
author = {Chinnathambi, S and Suresh, S and Velmurugan, G and Mishra, A},
title = {Alzheimer's disease: Extracellular Tau internalization in neuro-glial axis and its propagation mechanisms.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {1-31},
doi = {10.1016/bs.ai.2025.11.004},
pmid = {42629121},
issn = {1557-8445},
mesh = {Humans ; *tau Proteins/metabolism ; Animals ; *Alzheimer Disease/metabolism/pathology/immunology ; *Astrocytes/metabolism/pathology ; *Microglia/metabolism/pathology/immunology ; *Neuroglia/metabolism ; *Neurons/metabolism/pathology ; Inflammasomes/metabolism ; Oxidative Stress ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; },
abstract = {Tau is a protein associated with microtubules that is essential to the central nervous system's extracellular and intracellular functions. Aberrant post-translational changes cause Tau to dissociate from microtubules in pathological circumstances like Tauopathies and also in AD (AD). The free Tau can diffuse into the extracellular space, contributing to neurofibrillary tangles formation and paired helical filaments. Moreover, pathogenic Tau can spread in a prion-like manner from diseased neurons to healthy ones exacerbating Tau pathology. By stimulating the NLRP3 inflammasome and other pathways, extracellular Tau has an impact on microglia. This, in turn, triggers inflammatory responses and leads to neuroinflammation. Astrocytes, the predominant brain cells, absorb extracellular Tau and undergo morphological and functional changes that result in the production of neurotoxic compounds, which ultimately cause neurodegeneration. The uptake of Tau by astrocytes results in a proinflammatory phenotype and cellular senescence, which intensify neuroinflammatory processes and oxidative stress and accelerate the advancement of neurodegenerative illnesses.},
}

Humans
*tau Proteins/metabolism
Animals
*Alzheimer Disease/metabolism/pathology/immunology
*Astrocytes/metabolism/pathology
*Microglia/metabolism/pathology/immunology
*Neuroglia/metabolism
*Neurons/metabolism/pathology
Inflammasomes/metabolism
Oxidative Stress
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism

@article {pmid42629123,
year = {2026},
author = {Chidamabram, H and Ananathanarayana, V and Chinnathambi, S},
title = {G-Protein coupled receptor-mediated internalization and endosomal sorting of Tau-GPCR complex in microglia.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {147-173},
doi = {10.1016/bs.ai.2025.11.003},
pmid = {42629123},
issn = {1557-8445},
mesh = {Humans ; *Microglia/metabolism/immunology ; *tau Proteins/metabolism ; Animals ; *Alzheimer Disease/metabolism/immunology/pathology ; *Receptors, G-Protein-Coupled/metabolism ; *Endosomes/metabolism ; *Receptors, Purinergic P2Y12/metabolism ; Endocytosis ; Protein Transport ; },
abstract = {Microglia are the resident immune cells of the central nervous system (CNS), which are in constant surveillance of the brain microenvironment to maintain tissue homeostasis. Microglia play significant role both in the physiological and pathological conditions of the brain. Alzheimer's Disease (AD) is a neurodegenerative disease that includes progressive dementia and cognitive deficits. The two main culprits of AD are extracellular amyloid-β plaques and neurofibrillary tangles formed by Tau protein. In AD brain, intrinsically disordered Tau undergoes rapid oligomerization and self-aggregates to form filamentous species. Clearance of these toxic species is mainly performed by microglia, which can sense through various receptors such as Toll-like receptors (TLRs), G-Protein coupled receptor (GPCRs), purinergic receptors, etc. One such receptor is P2Y12R, a purinergic receptor whose expression is restricted to microglia in CNS. In this review, we envisioned providing an insight into the involvement of P2Y12R, a purinergic cell surface receptor that facilitates the internalization of Tau along with the other mechanisms of Tau clearance in microglia. Exploring these receptors and elucidating the mechanisms underlying Tau transmission could pave the way for the development of innovative therapeutic approaches aimed at impeding the spread of Tau pathology in neurodegenerative diseases.},
}

Humans
*Microglia/metabolism/immunology
*tau Proteins/metabolism
Animals
*Alzheimer Disease/metabolism/immunology/pathology
*Receptors, G-Protein-Coupled/metabolism
*Endosomes/metabolism
*Receptors, Purinergic P2Y12/metabolism
Endocytosis
Protein Transport

@article {pmid42629124,
year = {2026},
author = {Chinnathambi, S and Adityan, A and Chandrashekar, M and Velmurugan, G},
title = {iPSC-derived neurospheres: A cellular platform for Tau and Alzheimer's disease immunotherapy.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {175-203},
doi = {10.1016/bs.ai.2025.11.001},
pmid = {42629124},
issn = {1557-8445},
mesh = {Humans ; *Alzheimer Disease/therapy/immunology/metabolism/pathology ; *Induced Pluripotent Stem Cells/metabolism ; *tau Proteins/metabolism/immunology ; Animals ; *Neurons/metabolism ; Amyloid beta-Peptides/metabolism ; Microglia/metabolism ; *Immunotherapy/methods ; Astrocytes/metabolism ; },
abstract = {Alzheimer's disease is the most prevalent type of dementia, which is characterized by a progressive loss of memory and cognitive impairment. The internalization of extracellular Tau and Amyloid-β-induced pluripotent stem cells plays a crucial role in understanding the AD pathology. iPSC-derived neuron, microglia, and astrocyte are used as models to study the spreading of pathological proteins and their contribution in the disease progression. iPSC-derived neurons serve as an essential model for studying AD, particularly in relation to Tau aggregation, prion-like propagation, and the toxic effects of oligomeric amyloid beta. Extracellular Tau, along with oligomeric amyloid beta, enters neurons via endocytosis and macropinocytosis, leading to cellular abnormalities, oxidative stress, and dysfunction in neurons. Additionally, iPSC-derived microglia provide insights into neuroinflammatory responses and neurotoxic effects of Tau aggregation and Amyloid-β, highlighting their combined role in Alzheimer's pathology. Extracellular Tau internalization by microglia involves phagocytosis and exhibits activation response to Tau aggregates, releasing cytokines and undergoing calcium homeostasis. iPSC-derived astrocytes demonstrated a reactive state and disruption in calcium homeostasis upon the exposure of the pathological proteins, contributing to neurodegeneration. Further, the mechanisms of Tau and Amyloid-β internalization in iPSC-derived cells provide insights into disease progression and highlights potential therapeutic targets for neurodegenerative disease.},
}

Humans
*Alzheimer Disease/therapy/immunology/metabolism/pathology
*Induced Pluripotent Stem Cells/metabolism
*tau Proteins/metabolism/immunology
Animals
*Neurons/metabolism
Amyloid beta-Peptides/metabolism
Microglia/metabolism
*Immunotherapy/methods
Astrocytes/metabolism

@article {pmid42629128,
year = {2026},
author = {Saini, V and Mukherjee, S and Vora, C and Jindal, H and Jha, HC},
title = {Microglia in Alzheimer's disease: Insights into disease progression and therapy.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {283-306},
doi = {10.1016/bs.ai.2026.06.004},
pmid = {42629128},
issn = {1557-8445},
mesh = {*Microglia/immunology/metabolism/pathology ; Humans ; *Alzheimer Disease/therapy/metabolism/pathology/immunology ; Animals ; Disease Progression ; Receptors, Immunologic/metabolism ; Membrane Glycoproteins/metabolism ; Metabolic Reprogramming ; Cellular Senescence ; },
abstract = {The role of microglia, once seen as bystanders, has recently shifted to that of central regulators in disease pathology. The shift has been observed in M1/M2-polarized microglia to multiple configurations, including disease-associated microglia (DAM), lipid-droplet-accumulating microglia (LDAM), senescent microglia, and interferon-responsive microglia. This chapter provides a comprehensive synthesis of microglial biology across multiple interfaces, including transcriptomic, lipid-associated metabolic, cell senescence, and metabolic reprogramming. Metabolic disharmony in microglia occurs when lipid dysregulation and inflammasome activation occurs, leading to chronic inflammation beyond the basic phagocytic repair function of microglia. The TREM2-associated therapeutic trajectory also shows a translational gap with mechanistic and clinical benefits. We also identify the need for critical disease-associated microglial biomarkers and intervention strategies. Moreover, advanced iPSC-derived microglia and chimeric models often yield specialized organoid co-cultures, accelerating microglia-mediated therapeutic studies. Collectively, this chapter entails microglia as a central player in AD. This positions microglia biology as a metabolically plastic, spatially organized immune-regulated microenvironment that can efficiently aid in reprogramming and AD therapeutics.},
}

*Microglia/immunology/metabolism/pathology
Humans
*Alzheimer Disease/therapy/metabolism/pathology/immunology
Animals
Disease Progression
Receptors, Immunologic/metabolism
Membrane Glycoproteins/metabolism
Metabolic Reprogramming
Cellular Senescence

@article {pmid42629129,
year = {2026},
author = {Sha, L and Jha, S},
title = {Microglia extracellular traps (MiETs) in Neurodegeneration: Mechanisms, Evidence Gaps, and Untapped Therapeutic Promise.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {307-341},
doi = {10.1016/bs.ai.2026.04.008},
pmid = {42629129},
issn = {1557-8445},
mesh = {Humans ; *Extracellular Traps/immunology/metabolism ; *Microglia/immunology/metabolism ; Animals ; *Neurodegenerative Diseases/immunology/therapy/metabolism/pathology ; Histones/metabolism ; Signal Transduction ; Neuroinflammatory Diseases/immunology ; },
abstract = {Microglia are the resident myeloid cells of the central nervous system, they play essential roles in neural tissue homeostasis, including synaptic pruning, clearance of debris and protein aggregates, and regulation of neuroinflammatory processes. In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, microglial activation and chronic glial-driven inflammation contribute substantially to neuronal dysfunction and loss. Beyond these well-characterised functions, recent evidence indicates that microglia can release chromatin-based extracellular traps (microglia extracellular traps, or MiETs), similar to the neutrophil extracellular traps (NETs) observed in peripheral immunity. Microglia ETs are induced by stimuli such as dopamine and microbial infection, dependent or independent of NADPH oxidase/ROS pathways and histone citrullination. This chapter provides a detailed examination of MiET formation, triggers, intracellular signalling, and structural components, as well as contribution to neurodegenerative pathology. Potential mechanisms include amplification of neuroinflammation via extracellular histones and proteases, disruption of the blood-brain barrier and extracellular matrix, synaptic damage, and possible facilitation of spread of misfolded protein aggregates. We situate MiET formation within the broader microglial functional repertoire (phagocytosis, cytokine production, synaptic stripping) and focus on how ET-dominant responses may compromise homeostatic or neuroprotective roles. The chapter reviews evidence from disease models, highlights key gaps and discusses translational implications. Targeting MiET formation or promoting the clearance of MiETs represents promising, yet unexplored, therapeutic avenues in neurodegenerative disease. By focusing on MiETs, this work expands the conceptual framework for microglial pathogenicity and invites future mechanistic and translational research.},
}

Humans
*Extracellular Traps/immunology/metabolism
*Microglia/immunology/metabolism
Animals
*Neurodegenerative Diseases/immunology/therapy/metabolism/pathology
Histones/metabolism
Signal Transduction
Neuroinflammatory Diseases/immunology

@article {pmid42629135,
year = {2026},
author = {Ananathanarayana, V and Upadhyay, R and Illanad, GH and Krishnan, D and Bochageri, NP and Sevanan, M and Bagewadi, Z and Sivasamy, R and Chinnathambi, S},
title = {Chemokine receptor CX3CR1 modulates microglial activity through Tau and amyloid-β interactions in Alzheimer's disease.},
journal = {Advances in immunology},
volume = {171},
number = {},
pages = {83-108},
doi = {10.1016/bs.ai.2025.11.002},
pmid = {42629135},
issn = {1557-8445},
mesh = {Humans ; *Alzheimer Disease/metabolism/immunology/pathology ; *Microglia/metabolism/immunology ; *CX3C Chemokine Receptor 1/metabolism ; *tau Proteins/metabolism ; *Amyloid beta-Peptides/metabolism ; Animals ; Signal Transduction ; Chemokine CX3CL1/metabolism ; Neurons/metabolism ; },
abstract = {Alzheimer's disease is one of the most prevalent forms of dementia characterized by neurocognitive decline. Key proteins involved in the progression of disease is amyloid-β and Tau. Abnormal accumulation of amyloid-β senile plaques and Tau neurofibrillary tangles are characteristic features of AD which drives synaptic dysfunction and leads to cognitive decline. Recent studies emphasizes the importance of G-protein coupled receptors in regulating microglial cells and has diverse functions in modulating AD, particularly in the clearance of these pathological proteins. Among these GPCRs, the chemokine receptor CX3CR1 has a critical role at the intersection of pathological proteins and microglial signalling. CX3CR1 receptor mediated signalling influences interaction between microglia and neuron mediating microglial uptake and processing of Aβ and Tau. Aging is also one of the risk factors of AD which alters CX3CR1 signalling, thereby exacerbating disease progression. This review highlights the multifaceted role of CX3CR1 in Tau and Aβ pathology and outlines its signalling mechanisms. Importantly, this review emphasizes the therapeutic potential of targeting the CX3CL1-CX3CR1 axis and involved in protein clearance and reduces neuroinflammation preserving synaptic function, offering a promising way to prevent AD.},
}

Humans
*Alzheimer Disease/metabolism/immunology/pathology
*Microglia/metabolism/immunology
*CX3C Chemokine Receptor 1/metabolism
*tau Proteins/metabolism
*Amyloid beta-Peptides/metabolism
Animals
Signal Transduction
Chemokine CX3CL1/metabolism
Neurons/metabolism

@article {pmid42629343,
year = {2026},
author = {Moon, HE and Lee, YS and Roh, S and Allick, C and Sites, KW and Rote, S and Stone, ST},
title = {Cultural Contexts of Caregiving: Exploring Alzheimer's Disease Experiences and Service Needs Among American Indian Communities.},
journal = {The Gerontologist},
volume = {},
number = {},
pages = {},
doi = {10.1093/geront/gnag201},
pmid = {42629343},
issn = {1758-5341},
abstract = {BACKGROUND AND OBJECTIVES: American Indian and Alaska Native (AIAN) experience disproportionately high rates of Alzheimer's disease and related dementias (ADRD), yet little research examines caregiving experiences and service needs within these communities. Guided by the Sociocultural Stress and Coping Model, this study explored dementia caregiving experiences, cultural contexts, and service needs among American Indian community members, tribal health professionals, and leaders in a Northern Plains tribal community using a community-based participatory research approach.

RESEARCH DESIGN AND METHODS: In 2024, seven focus groups were conducted with 60 American Indian adults (48 community members, 12 health professionals/tribal leaders) living in the Northern Plains. Semi-structured focus groups explored caregiving experiences, cultural beliefs, and service needs. A participant background survey captured demographics and care characteristics. Qualitative data were analyzed using conceptual content analysis with iterative team-based coding.

RESULTS: Three themes emerged across positive, negative, and service need domains. Community members emphasized cultural duty, love/reciprocity, and humor as coping mechanisms. Negative experiences included emotional and intergenerational trauma from childhood dementia exposure, and safety/supervision challenges. Critical service needs included medical guidance, community-based education, and respite services. Health professionals and tribal leaders navigated dual clinician-caregiver identities while advocating for system-level reforms. Both groups identified geographic barriers and resource scarcity.

DISCUSSION AND IMPLICATIONS: Findings reveal cultural strengths sustaining caregiving amid substantial systemic barriers. Effective interventions must be family-centered, community-based, and strength-focused. Healthcare systems require fundamental realignment to accommodate Indigenous epistemologies.},
}

@article {pmid42629457,
year = {2026},
author = {Nonino, F and Vignatelli, L and Richard, E},
title = {Reply to "Pooling Alzheimer's disease: when methodological rigor risks obscuring biological complexity".},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {9},
pages = {},
pmid = {42629457},
issn = {1590-3478},
}

@article {pmid42629610,
year = {2026},
author = {Bundschuh, BF and Kley, F and Wang, Y and Strodel, B},
title = {Membrane Complexity and Phase Behavior Dictate the Stability of Membrane-Inserted Aβ42 Hexamers.},
journal = {Chemphyschem : a European journal of chemical physics and physical chemistry},
volume = {27},
number = {16},
pages = {e70538},
doi = {10.1002/cphc.70538},
pmid = {42629610},
issn = {1439-7641},
mesh = {*Amyloid beta-Peptides/chemistry/metabolism ; Molecular Dynamics Simulation ; *Lipid Bilayers/chemistry/metabolism ; *Peptide Fragments/chemistry/metabolism ; Phosphatidylcholines/chemistry ; Protein Stability ; *Cell Membrane/chemistry/metabolism ; },
abstract = {Protein-membrane interactions are vital to Alzheimer's pathogenesis, as lipid environments modulate both the aggregation and toxicity of amyloid-β (Aβ) peptides. Using atomistic molecular dynamics simulations, this study investigates the stability of an NMR-derived hexameric Aβ42 β-barrel in aqueous solution, a fluid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer, and a complex neuronal membrane. While the hexamer is unstable and conformationally heterogeneous in water, lipid environments provide essential structural reinforcement. Notably, the multicomponent neuronal membrane offers superior stabilization compared to POPC, supporting the β-barrel in a stable transmembrane conformation. This superior stability is driven by the rigid scaffolding of the liquid-ordered phase alongside specific electrostatic anchoring between the ethanolamine headgroups of the POPE component and the acidic Aβ42 residues E22/D23. We characterize a reciprocal relationship where the membrane stabilizes the β-barrel architecture, while the peptide induces localized lipid disorder and flip-flop translocation. Our findings demonstrate how membrane complexity and phase behavior dictate the stability of toxic Aβ42 oligomers, offering key insights into the membrane-mediated mechanisms of neurotoxicity.},
}

*Amyloid beta-Peptides/chemistry/metabolism
Molecular Dynamics Simulation
*Lipid Bilayers/chemistry/metabolism
*Peptide Fragments/chemistry/metabolism
Phosphatidylcholines/chemistry
Protein Stability
*Cell Membrane/chemistry/metabolism

@article {pmid42630070,
year = {2026},
author = {Alsharayri, S and Knox, S and Cutty, M and Mollalo, A},
title = {Dual eligibility and neuropsychiatric symptoms and treatment disparities among Medicare Part D beneficiaries with Alzheimer's disease and related dementias.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261478140},
doi = {10.1177/13872877261478140},
pmid = {42630070},
issn = {1875-8908},
abstract = {BackgroundNeuropsychiatric symptoms (NPS) are common and clinically consequential in Alzheimer's disease and related dementias (ADRD), yet their recognition and treatment may vary across socioeconomic groups. Dual-eligible Medicare-Medicaid beneficiaries represent a vulnerable population, but differences in NPS documentation and management remain unclear.ObjectiveTo examine whether dual eligibility is associated with differences in (1) documented NPS and (2) prescription fills among Medicare beneficiaries with ADRD who received home health (HH) care.MethodsWe conducted a cross-sectional study of 167,484 Medicare Part D beneficiaries with ADRD who received HH care and were identified using the Chronic Conditions Warehouse flag. Dual eligibility was the primary exposure. NPS were identified using diagnosis codes from medical claims. Prescription fills for NPS-related medications were identified using Medicare Part D prescription drug event data (≥2 prescription fills for anxiety-related medications and antidepressants). Logistic regression models estimated associations of dual eligibility with NPS documentation and prescription fills, adjusting for demographic characteristics, original Medicare entitlement, and comorbidity burden.ResultsDual-eligible beneficiaries comprised 30.7% of the cohort. Documented confusion and anxiety were the most prevalent symptoms. Dual-eligible beneficiaries had a higher prevalence of confusion (83.5% versus 82.0%) and anxiety (57.0% versus 53.2%) compared with Medicare-only beneficiaries. After adjustment, dual eligibility was associated with higher odds of documented confusion (aOR 1.18, 95% CI 1.14-1.22) and anxiety (aOR 1.19, 95% CI 1.15-1.22). Dual eligibility was also associated with slightly higher odds of anxiety-related prescription fills (aOR 1.21, 95% CI 1.17-1.26), whereas antidepressant prescription fills did not differ (aOR 1.00, 95% CI 0.95-1.05).ConclusionsDual eligibility was associated with modest differences in NPS documentation and prescription fills, suggesting differences in recognition and management of NPS among beneficiaries with ADRD.},
}

@article {pmid42630074,
year = {2026},
author = {Tu, T and Zhang, QL and Sun, ZP and Kang, C and Li, D and Huo, XH and Zhang, XJ and Zhang, Y and Cui, M and Pan, A and Wang, J and Yan, XX},
title = {Aberrant ɑSMA expression reveals broad mossy fiber reorganization integrating with tangle and plaque formation and mitoenergetic alteration in the human hippocampus.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71778},
doi = {10.1002/alz.71778},
pmid = {42630074},
issn = {1552-5279},
support = {#2021ZD0201103//Ministry of Science and Technology of China/ ; #2021ZD02018//Ministry of Science and Technology of China/ ; #82201595//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Plaque, Amyloid/pathology/metabolism ; Female ; *Hippocampus/pathology/metabolism ; *Actins/metabolism ; *Alzheimer Disease/pathology/metabolism ; Aged ; Male ; *Mossy Fibers, Hippocampal/pathology/metabolism ; Aged, 80 and over ; *Neurofibrillary Tangles/pathology/metabolism ; Electron Transport Complex IV/metabolism ; },
abstract = {INTRODUCTION: Neural network and bioenergetic abnormalities occur with Alzheimer's disease (AD) pathogenesis.

METHODS: We explored mossy fiber (MF) and mitoenergetic alteration using ɑ-smooth muscle actin (ɑSMA) and cytochrome c oxidase (COX) immunolabeling in human hippocampus relative to tangle and plaque formation by referring to Braak (0-VI) and Thal (0-5) staging scores.

RESULTS: In the brain group with Braak/Thal 0/0 scores (control), ɑSMA labeling occurred in CA3 and dentate gyrus. In groups with 1a to IV/0 and II to VI/1 to 5 scores, ɑSMA labeling appeared in CA2 to subiculum, with increased density in these and the dentate subregions. ɑSMA-labeled MF terminals infiltrated into ghost tangles co-expressing amyloidogenic markers and coexisted among β-secreatse-1 labeled neurites and amyloid beta plaques. COX immunolabeling was increased in CA2 to subiculum in the groups with 1a to IV/0 to 1 compared to 0/0.

DISCUSSION: MF reorganization/dystrophy develops and integrates with tangle and plaque formation and mitoenergetic alteration in the human hippocampus.},
}

Humans
*Plaque, Amyloid/pathology/metabolism
Female
*Hippocampus/pathology/metabolism
*Actins/metabolism
*Alzheimer Disease/pathology/metabolism
Aged
Male
*Mossy Fibers, Hippocampal/pathology/metabolism
Aged, 80 and over
*Neurofibrillary Tangles/pathology/metabolism
Electron Transport Complex IV/metabolism

@article {pmid42630075,
year = {2026},
author = {Stenberg, E and Cao, Y and Eliasson, B and Näslund, E},
title = {The effects of bariatric surgery on dementia in patients with diabetes and obesity.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71802},
doi = {10.1002/alz.71802},
pmid = {42630075},
issn = {1552-5279},
support = {//Region Örebro County, Åke Wiberg Foundation, and Region Stockholm/ ; },
mesh = {Humans ; *Bariatric Surgery ; *Obesity/surgery/epidemiology/complications ; *Dementia/epidemiology/prevention & control ; *Diabetes Mellitus, Type 2/epidemiology/complications/surgery ; Female ; Male ; Middle Aged ; Aged ; Incidence ; Risk Factors ; Registries ; Propensity Score ; },
abstract = {INTRODUCTION: Type 2 diabetes (T2D) and obesity are among the most important risk factors for dementia. Although weight loss is an important preventive strategy, the impact of metabolic and bariatric surgery (MBS) on dementia risk remains contradictory.

METHODS: We conducted a propensity score matched study using nationwide, high-quality clinical registries to compare the outcomes in patients with obesity and T2D who underwent MBS with matched controls who did not undergo surgery.

RESULTS: Over a mean follow-up of 9 years, MBS was associated with a reduced risk of dementia (15-year cumulative incidence 1.8% vs. 2.7%, subdistribution hazard ratio [SHR] 0.60, 95% CI 0.47-0.76). The incidence was lower for Alzheimer's disease (1.2% vs. 1.9%, SHR 0.56, 95% CI 0.41-0.76) and vascular dementia (0.4% vs. 0.7%, SHR 0.49, 95% CI 0.29-0.85), but increased for alcohol-related dementia (0.2% vs. 0.04%, SHR 3.67, 95%CI 1.33-10.14).

DISCUSSION: These findings suggest that the collected long-term effects of MBS may reduce the risk of developing dementia in individuals with obesity and T2D.},
}

Humans
*Bariatric Surgery
*Obesity/surgery/epidemiology/complications
*Dementia/epidemiology/prevention & control
*Diabetes Mellitus, Type 2/epidemiology/complications/surgery
Female
Male
Middle Aged
Aged
Incidence
Risk Factors
Registries
Propensity Score

@article {pmid42630093,
year = {2026},
author = {Lep, M and Plesingrova, K and Sedmik, J and Cesnarikova, S and Feole, M and Bernatik, O and Pozo Devoto, VM and Hribkova, H and Amruz Cerna, K and Fojtik, P and Vaskovicova, N and Bartova, S and Pospisilova, V and Vanova, T and Andersen, OM and Bohaciakova, D and Raska, J},
title = {SORL1 variant links endosomal amyloid precursor protein mis-sorting to axonal transport defects and neuronal dysfunction.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71782},
doi = {10.1002/alz.71782},
pmid = {42630093},
issn = {1552-5279},
support = {NU22J-08-00075//Agentura Pro Zdravotnický Výzkum České Republiky/ ; GA24-12028S//Grantová Agentura České Republiky/ ; LX22NPO5107//NextGenerationEU/ ; 101087124//HORIZON EUROPE Framework Programme/ ; 857560//Horizon 2020/ ; ADPriOMICS2023-087//EU Joint Programme - Neurodegenerative Disease Research/ ; MUNI/A/1738/2024//Lékařská fakulta, Masarykova univerzita/ ; },
mesh = {Humans ; *Amyloid beta-Protein Precursor/metabolism ; *Axonal Transport/genetics/physiology ; *Endosomes/metabolism ; *Neurons/metabolism/pathology ; *LDL-Receptor Related Proteins/genetics/metabolism ; *Membrane Transport Proteins/genetics/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Alzheimer Disease/genetics ; Protein Transport ; },
abstract = {INTRODUCTION: SORL1 encodes the sorting receptor SORLA, a major genetic contributor to Alzheimer's disease (AD). Although SORL1 loss disrupts endosomal trafficking and promotes amyloidogenic amyloid precursor protein (APP) processing, the functional consequences of specific missense variants in human neurons remain unclear.

METHODS: We used isogenic induced pluripotent stem cell (iPSC)-derived NGN2 neurons and 3D cerebral organoids carrying wild-type, SORL1 p.Y1816C knock-in, or SORL1 knockout alleles. We analyzed SORLA maturation and shedding, APP localization, amyloid-β (Aβ) secretion, endosomal morphology, axonal transport of Rab5+ endosomes and APP, and network activity.

RESULTS: The p.Y1816C variant impaired SORLA maturation and shedding and, together with knockout, caused enlarged early endosomes, APP retention, elevated Aβ secretion, amyloid deposition in organoids, axonal swellings, disrupted axonal transport, and neuronal hyperexcitability.

CONCLUSIONS: The SORL1 p.Y1816C variant is pathogenic in human neurons, and we reveal novel roles for SORLA in axonal transport and neuronal excitability. These findings highlight endosomal trafficking disruption as a central mechanism in AD pathogenesis.},
}

Humans
*Amyloid beta-Protein Precursor/metabolism
*Axonal Transport/genetics/physiology
*Endosomes/metabolism
*Neurons/metabolism/pathology
*LDL-Receptor Related Proteins/genetics/metabolism
*Membrane Transport Proteins/genetics/metabolism
Induced Pluripotent Stem Cells/metabolism
Alzheimer Disease/genetics
Protein Transport

@article {pmid42630134,
year = {2026},
author = {Kumar, A and Sharma, M and Su, Y and Singh, S and Tanley, JE and Casanova, R and Hsu, FC and Craft, S and Mielke, MM and Hughes, TM and Deep, G},
title = {Dissecting Alzheimer's proteomic landscape through NULISA profiling of brain cell-specific extracellular vesicles.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {8},
pages = {e71717},
doi = {10.1002/alz.71717},
pmid = {42630134},
issn = {1552-5279},
support = {75N92020D00001/NH/NIH HHS/United States ; HHSN268201500003I/NH/NIH HHS/United States ; N01-HC-95159/NH/NIH HHS/United States ; 75N92020D00005/NH/NIH HHS/United States ; N01-HC-95160/NH/NIH HHS/United States ; 75N92020D00002/NH/NIH HHS/United States ; N01-HC-95161/NH/NIH HHS/United States ; 75N92020D00003/NH/NIH HHS/United States ; N01-HC-95162/NH/NIH HHS/United States ; 75N92020D00006/NH/NIH HHS/United States ; N01-HC-95163/NH/NIH HHS/United States ; 75N92020D00004/NH/NIH HHS/United States ; N01-HC-95164/NH/NIH HHS/United States ; 75N92020D00007/NH/NIH HHS/United States ; N01-HC-95165/NH/NIH HHS/United States ; N01-HC-95166/NH/NIH HHS/United States ; N01-HC-95167/NH/NIH HHS/United States ; N01-HC-95168/NH/NIH HHS/United States ; N01-HC-95169/NH/NIH HHS/United States ; /HL/NHLBI NIH HHS/United States ; R01AG054069/TR/NCATS NIH HHS/United States ; R01AG058969/TR/NCATS NIH HHS/United States ; P30AG072947/TR/NCATS NIH HHS/United States ; 1R01AG084696/TR/NCATS NIH HHS/United States ; 1RF1AG068629/TR/NCATS NIH HHS/United States ; /AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; *Extracellular Vesicles/metabolism ; *Proteomics/methods ; *Brain/metabolism/pathology ; Biomarkers/blood/metabolism ; Cognitive Dysfunction/metabolism ; Neurons/metabolism ; Microglia/metabolism ; Astrocytes/metabolism ; *Proteome ; Endothelial Cells/metabolism ; Oligodendroglia/metabolism ; },
abstract = {INTRODUCTION: Blood-based biomarkers are essential for early detection, monitoring, and therapeutic development in Alzheimer's disease (AD) and related dementia (ADRD), but current assays lack brain cell specificity and sensitivity to low-abundant proteins.

METHOD: We isolated the following brain cell-derived small extracellular vesicles (sEV) from the plasma of individuals with normal cognition (CN), mild cognitive impairment (MCI), or ADRD: neurons (NDE), astrocytes (ADE), microglia (MDE), oligodendrocytes (ODE), pericytes (PDE), and endothelial cells (EDE). Using NULISAseq, we profiled 122 proteins, spanning AD pathology, neurodegeneration, and neuroinflammation.

RESULTS: sEV proteomes showed distinct brain cell-type-specific signatures. MCI exhibited early dysregulation of neuroprotective, inflammatory, and vascular markers in NDE, MDE, and ODE. ADRD displayed broader alteration tau, amyloid, neuroinflammation, vascular dysfunction, and synaptic loss across multiple sEV populations.

DISCUSSION: Combining NULISAseq with brain cell-derived plasma sEV enables the detection of multicellular molecular changes in ADRD, supporting their use as a minimally invasive platform for biomarker discovery.},
}

Humans
*Alzheimer Disease/metabolism/pathology
*Extracellular Vesicles/metabolism
*Proteomics/methods
*Brain/metabolism/pathology
Biomarkers/blood/metabolism
Cognitive Dysfunction/metabolism
Neurons/metabolism
Microglia/metabolism
Astrocytes/metabolism
*Proteome
Endothelial Cells/metabolism
Oligodendroglia/metabolism

@article {pmid42630226,
year = {2026},
author = {Kim, H and Parker, C and Severance, JJ and Wiechmann, A},
title = {When mild impairment is not safe: mini-mental state examination scores of ≤21 are associated with emergency response failure.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1916712},
doi = {10.3389/fnagi.2026.1916712},
pmid = {42630226},
issn = {1663-4365},
abstract = {INTRODUCTION: Unrecognized emergency-response deficits contribute to preventable harm and loss of independence in older adults with cognitive decline. Although the Mini-Mental State Examination (MMSE) is widely used to assess global cognition, clinicians often use MMSE scores to inform judgments about everyday functioning. However, the relationship between MMSE performance and emergency-response ability remains unclear. The Test of Executive Functioning in an Emergency (TEFE) is a brief, performance-based assessment that evaluates a patient's ability to relay critical information and contact emergency services. This study examined whether an MMSE threshold was associated with failure on TEFE 911 tasks.

METHODS: A retrospective analysis included 905 patients from a university-affiliated memory clinic with Alzheimer's disease, vascular dementia, mixed dementia, mild cognitive impairment, or normal cognition. Associations between MMSE scores and TEFE 911 knowledge and behavioral task failure were examined using correlation, adjacent-score comparisons, receiver operating characteristic (ROC) analyses, Youden's J, and multivariable logistic regression adjusted for demographic and diagnostic covariates.

RESULTS: MMSE and TEFE scores were moderately correlated (r = 0.596, p < 0.0001). Failure rates were higher at MMSE scores of 21 than 22. ROC analyses demonstrated good discrimination for 911 task failure (AUC = 0.860-0.867). An MMSE cutoff of ≤21 yielded 61.9% sensitivity and 88.9% specificity for failure on 911 tasks and remained independently associated with failure after adjustment (adjusted OR = 3.71, 95% CI: 1.82-7.56).

DISCUSSION: Patients with MMSE scores ≤21 may warrant further performance-based assessment of emergency-response ability. Prospective studies should determine whether this threshold predicts real-world safety outcomes.},
}

@article {pmid42630294,
year = {2026},
author = {Shafi, S and Ansari, GA},
title = {Developing artificial intelligence-based techniques for brain MRI image segmentation.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1894751},
doi = {10.3389/fnins.2026.1894751},
pmid = {42630294},
issn = {1662-4548},
abstract = {INTRODUCTION: Brain MRI image segmentation is essential for the accurate diagnosis and treatment of neurological disorders, including brain tumors, Alzheimer's disease, and multiple sclerosis. Artificial intelligence (AI), particularly deep learning, has emerged as an effective approach for improving the precision and efficiency of medical image segmentation while reducing manual effort.

METHODS: This study utilized a publicly available Kaggle brain MRI dataset containing labeled images for supervised learning. A Convolutional Neural Network (CNN)-based framework was developed for automatic brain MRI segmentation. The methodology incorporated preprocessing techniques, including noise removal, normalization, and data augmentation, to improve image quality and model performance. The proposed model was evaluated using Accuracy, Dice Score, and Intersection over Union (IoU).

RESULTS: Experimental results demonstrated that the proposed AI-based segmentation framework achieved high segmentation accuracy and effectively distinguished normal brain tissue from abnormal regions. The model outperformed conventional image-processing methods by providing improved segmentation precision, reducing manual intervention, and enhancing the reliability of medical image analysis.

DISCUSSION: The findings demonstrate the potential of AI-based deep learning techniques for automated brain MRI segmentation in clinical applications. The proposed framework can support clinicians by improving diagnostic accuracy and reducing processing time. Future work will focus on implementing more advanced deep learning architectures and expanding the dataset to further improve segmentation performance and clinical applicability.},
}

@article {pmid42630395,
year = {2026},
author = {Fan, R and Wu, X},
title = {From fragmented neurotechnologies to closed-loop brain health systems: integrating artificial intelligence, digital health, digital twins, and advanced materials for brain disorders.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {14},
number = {},
pages = {1904561},
doi = {10.3389/fbioe.2026.1904561},
pmid = {42630395},
issn = {2296-4185},
abstract = {Brain disorders have traditionally been managed through fragmented clinical pathways in which diagnosis, monitoring, intervention, and long-term follow-up are treated as separate processes. This paradigm is increasingly insufficient for conditions such as Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, glioma, epilepsy, and neuropsychiatric disorders, whose trajectories are dynamic, heterogeneous, and strongly shaped by biological, behavioral, environmental, and health-system factors. Recent advances in artificial intelligence, digital health, digital twin modeling, and advanced biomaterials provide an opportunity to move beyond isolated technological applications toward integrated brain health systems. In this Perspective, we argue that the major translational opportunity is not simply to apply artificial intelligence to neuroimaging, use wearable devices for neurological monitoring, or develop biomaterials for brain repair in parallel. Rather, the field should aim to build closed-loop systems in which computational models identify disease states, digital platforms continuously update patient trajectories, and advanced materials deliver adaptive therapeutic or regenerative interventions. We propose that future progress depends on three related shifts: moving from episodic diagnosis to longitudinal brain-state modeling; redefining advanced materials as programmable therapeutic interfaces rather than passive carriers; and evaluating success at the level of health-system integration rather than single-device performance. This framework may help reorient brain disease innovation from fragmented neurotechnologies toward clinically deployable, patient-specific, and dynamically adaptive brain health systems.},
}

@article {pmid42630537,
year = {2026},
author = {},
title = {Correction to "Translational Medicine in Alzheimer's Disease: The Journey of Donanemab From Discovery to Clinical Application".},
journal = {Chronic diseases and translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1002/cdt3.70063},
pmid = {42630537},
issn = {2589-0514},
abstract = {[This corrects the article DOI: 10.1002/cdt3.155.].},
}

@article {pmid42630799,
year = {2026},
author = {Peng, L and Wu, Z and Yuan, X and Zhou, C and Fu, H},
title = {The potential connection between inflammatory bowel disease and Alzheimer's disease: mechanistic insights and therapeutic implications.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1910604},
doi = {10.3389/fimmu.2026.1910604},
pmid = {42630799},
issn = {1664-3224},
mesh = {Humans ; *Alzheimer Disease/immunology/metabolism/epidemiology/drug therapy ; *Inflammatory Bowel Diseases/immunology/metabolism/drug therapy/epidemiology ; Animals ; Gastrointestinal Microbiome/immunology ; Dysbiosis ; Glymphatic System/metabolism/immunology ; },
abstract = {Inflammatory bowel disease (IBD) and Alzheimer's disease (AD) are two chronic conditions previously considered pathologically unrelated. However, accumulating epidemiological evidence suggests that patients with IBD may have an elevated risk. This review systematically analyzes the mechanistic links between IBD and AD, emphasizing the roles of gut microbiota dysbiosis, systemic and neuroinflammation, and glymphatic dysfunction. We propose a putative conceptual framework incorporating the 'gut-glymphatic axis' as a potential conduit through which IBD-associated microbial and immune perturbations may influence AD pathology. Key pathways include short-chain fatty acids, tryptophan metabolites, trimethylamine N-oxide, and bile acids, all of which modulate neuroinflammation and amyloid-β clearance. Additionally, circadian disruption and impaired aquaporin-4 polarity in the glymphatic system may represent novel links between intestinal inflammation and neurodegenerative changes. Preclinical animal models suggest that colitis exacerbates AD-like pathology via NLRP3 inflammasome activation, neutrophil infiltration, and microglial dysfunction. Natural bioactive compounds-such as ginsenosides, curcumin, baicalin, berberine, and magnolol-show dual therapeutic potential in both IBD and AD by targeting shared inflammatory and microbiota pathways. However, validated comorbidity models and clinical trials are lacking. This review provides a scientifically grounded basis for future mechanistic studies and integrated interventions for IBD-AD comorbidity.},
}

Humans
*Alzheimer Disease/immunology/metabolism/epidemiology/drug therapy
*Inflammatory Bowel Diseases/immunology/metabolism/drug therapy/epidemiology
Animals
Gastrointestinal Microbiome/immunology
Dysbiosis
Glymphatic System/metabolism/immunology

@article {pmid42630903,
year = {2026},
author = {Hung, KC and Weng, HL and Lai, YC and Chen, IW},
title = {U-shaped pattern in the association between serum magnesium levels and long-term dementia risk after traumatic brain injury: a retrospective cohort study.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1870929},
doi = {10.3389/fnut.2026.1870929},
pmid = {42630903},
issn = {2296-861X},
abstract = {BACKGROUND: In the general population, abnormal serum magnesium levels are associated with an increased risk of cognitive decline and dementia. However, whether this association extends to patients with traumatic brain injury (TBI), a population with distinct neurobiological vulnerabilities, remains unknown.

METHODS: Using the TriNetX Global Collaborative Network, we identified adults aged ≥50 years with a history of intracranial injury (ICD-10-CM: S06). Patients with repeatedly low serum magnesium levels (< 1.7 mg/dL, two measurements within 1 year) were compared with those with normal levels (1.70-2.20 mg/dL) using 1:1 propensity score matching. A 1-year landmark period was applied to reduce the reverse causation. The primary outcome was incident dementia over 10 years of follow-up. The secondary outcomes included dementia subtypes, cognitive dysfunction, and all-cause mortality. To explore a potential U-shaped relationship, a parallel analysis was conducted comparing patients with repeatedly high magnesium levels (>2.20 mg/dL) with the same reference cohort. Sensitivity analyses, subgroup analyses by sex and TBI severity, and multivariable Cox regression were performed.

RESULTS: After matching, 11,716 patients were retained in each cohort. Low magnesium levels were associated with a higher 10-year risk of incident dementia [2.53% vs. 1.78%; hazard ratio (HR) 1.62, 95% confidence interval (CI), 1.36-1.94; p < 0.001]. Among the secondary outcomes, associations were observed for vascular dementia (HR 1.97, p = 0.001), other dementia types (HR 1.63, p < 0.001), cognitive dysfunction (HR 1.43, p = 0.009), and all-cause mortality (HR 1.29, p < 0.001), whereas Alzheimer's disease did not reach significance (HR 1.43, p = 0.075). High magnesium levels were similarly associated with an increased risk of dementia (HR 1.57, p < 0.001). The findings were consistent across sensitivity and subgroup analyses and after multivariable adjustment (adjusted HR 1.50, p < 0.001).

CONCLUSION: In adults with prior TBI, both low and high serum magnesium levels were associated with a greater long-term risk of dementia, suggesting a U-shaped relationship. Prospective studies are needed to determine whether monitoring or modifying magnesium status can alter the post-traumatic dementia trajectory.},
}

@article {pmid42630973,
year = {2026},
author = {Kaur, B and Nada, H and Zhang, L and Gabr, M},
title = {Structure-Guided Optimization of CHI3L1 Modulators Reveals G721-0377 as a Lead Compound for Restoring Astrocyte Function in Alzheimer's Disease.},
journal = {ACS bio & med chem Au},
volume = {6},
number = {4},
pages = {329-341},
doi = {10.1021/acsbiomedchemau.5c00279},
pmid = {42630973},
issn = {2694-2437},
abstract = {Alzheimer's disease (AD) involves astrocytic dysfunction characterized by impaired lysosomal activity, defective amyloid clearance, and neuroinflammation, processes strongly regulated by the inflammatory effector CHI3L1. G721-0282, a reported CHI3L1-binding small molecule with demonstrated modulation of downstream signaling pathways including MAPK and STAT3, provides a validated chemical starting point for targeting CHI3L1-driven astrocytic pathology in AD, but it exhibits suboptimal potency and drug-like properties that limit its translational potential. We therefore performed a virtual screening of commercially available analogues of G721-0282 to enable structure-guided optimization, generating a detailed structure-activity map, and prioritizing 24 derivatives. Biophysical analyses identified compound G721-0377 as the most promising candidate, with optimized substitutions resulting in enhanced CHI3L1-binding affinity (K d = 45 μM), representing a ∼3-5-fold improvement over related analogs (K d = 65-236 μM). Compound G721-0377 also exhibited favorable physicochemical and pharmacokinetic properties, including improved solubility, balanced permeability, reduced microsomal clearance, and an enhanced cardiac safety margin. Given their micromolar potency, all functional studies were conducted in vitro. Functionally, G721-0377 uniquely reversed CHI3L1-induced astrocytic dysfunction, restoring amyloid uptake, lysosomal proteolysis and acidification, suppressing CHI3L1 and IL-6 secretion, and inhibiting NF-κB activation to levels comparable to a neutralizing anti-CHI3L1 antibody. Collectively, these findings establish G721-0377 as a promising early stage lead compound with improved affinity, safety, and robust functional efficacy, supporting its further development as a disease-modifying therapeutic for AD.},
}

@article {pmid42631058,
year = {2026},
author = {Medrano, M and Pacheco-Herrero, M and Borges, Z and Laureano, JR and Dominguez-Garcia, J and Gil-Ventura, R and Castro-Tejada, G},
title = {Characterization of the intestinal microbial profile in mild cognitive impairment and Alzheimer's disease.},
journal = {Dementia & neuropsychologia},
volume = {20},
number = {},
pages = {e20250440},
doi = {10.1590/1980-5764-DN-2025-0440},
pmid = {42631058},
issn = {1980-5764},
abstract = {UNLABELLED: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are major contributors to dementia, with growing prevalence in Latin America. Evidence suggests that gut microbiota alterations may influence neurodegeneration, but data on Hispanic population are lacking.

OBJECTIVE: Characterize gut microbiota in individuals with AD, MCI, and controls in the Dominican Republic, exploring clinical, demographic, and dietary associations.

METHODS: Prospective-translational study including 88 participants aged ≥60 years. Performed clinical, cognitive, and functional assessments. Stool samples analyzed using 16S rRNA gene sequencing. Bioinformatic processing using Quantitative Insights into Microbial Ecology Version 2 (QIIME2) and R. Alpha and beta diversity, taxonomy, and differential abundance were evaluated. Dietary influences were assessed using PERMANOVA.

RESULTS: No significant differences in alpha diversity (Shannon index 4-5, Simpson index 0.94-0.99, p>0.05) or beta diversity (p>0.05) were observed between groups. Firmicutes (51.9%) and Bacteroidota (34.1%) dominated the microbiota. Higher Desulfobacterota abundance in MCI and AD (0.54 and 0.61%, respectively, vs. 0.34% in controls; p<0.05). The Firmicutes/Bacteroidota ratio was lower in men with MCI (1.09) compared to controls and AD (1.70). MCI and AD were associated with increased levels of the genera Bilophila, Odoribacter, and Parabacteroides (p<0.05) and reduced levels of Mitsuokella and Eubacterium ruminantium. Dietary interactions, e.g., mango, lettuce, and carrot, influenced specific taxa (p<0.05).

CONCLUSION: This study pioneers gut microbiota characterization in AD and MCI in the Dominican Republic, identifying microbial alterations in cognitive impairment and highlighting regional dietary and ethnic factors. Longitudinal and multi-omics studies are warranted to clarify causality and therapeutic potential.},
}

@article {pmid42631064,
year = {2026},
author = {Tao, X and Nassuna, T and Zhai, RG},
title = {Polyamine Metabolism in Brain Health and Disease.},
journal = {Neuropharmacology and therapy},
volume = {3},
number = {},
pages = {49-62},
doi = {10.15212/npt-2025-0028},
pmid = {42631064},
issn = {2990-8779},
abstract = {Polyamines, primarily spermidine and spermine, are small polycationic molecules essential for cell growth, signaling, and survival. Through electrostatic interactions with nucleic acids, lipids, and proteins, they regulate gene expression, organelle function, and adaptive responses to environmental cues. Polyamine metabolism also intersects with a myriad of other cellular pathways, including methionine, acetyl-CoA, and oxidative stress pathways, and is therefore involved in epigenetic control, cellular metabolism, and stress-response regulation. In the brain, beyond these general cellular functions, polyamines act as dynamic modulators of neurodevelopment, neural maintenance, and synaptic plasticity by influencing local proteostasis, transmitter release, and ion channel activity in both neurons and glia. Emerging evidence indicates that disruption of polyamine homeostasis contributes to neurological disorders as diverse as rare inborn errors of metabolism and common neurodegenerative diseases. Mutations in polyamine metabolic or transport genes lead to syndromes characterized by intellectual disability, hypotonia, movement disorders, and neurodegeneration; therefore, polyamine balance is critical for brain development and maintenance. In conditions such as Alzheimer's and Parkinson's diseases, dysregulated polyamine synthesis, catabolism, or lysosomal transport perturbs autophagic flux and proteostasis, thereby promoting Tau and α-synuclein aggregation, oxidative stress, and neuronal loss. Multi-omics analyses have further revealed that polyamine metabolism shapes glial inflammatory responses. Therapeutically, modulation of polyamine metabolism offers multiple intervention points. Spermidine supplementation or administration of polyamine analogues has been found to enhance autophagy and improve cognitive performance in models of aging and Alzheimer's disease. Additional strategies to reestablish metabolic equilibrium and support neuronal resilience include targeted manipulation of key enzymes, such as ornithine decarboxylase 1 (ODC1), spermidine/spermine acetyltransferase 1 (SAT1), spermine oxidase (SMOX), and spermine synthase (SMS), or restoration of lysosomal polyamine export via ATP13A2. This review synthesizes current understanding of polyamine metabolism in brain health and disease, by integrating molecular, cellular, and systems-level perspectives, and further highlights emerging therapeutic directions aimed at harnessing this pathway to mitigate neurological pathology.},
}

@article {pmid42631141,
year = {2026},
author = {O'Neill, HM and Kumar, K and Rathore, VS},
title = {From plate to brain: role of mediators and moderators on the impact of diet on Alzheimer's disease.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1898935},
doi = {10.3389/fnut.2026.1898935},
pmid = {42631141},
issn = {2296-861X},
abstract = {Diet represents one of the most clinically accessible modifiable risk factors for Alzheimer's disease (AD), with potential to influence disease onset and progression through multiple biological pathways. Emerging evidence from observational studies suggests that adherence to specific dietary patterns, including the Mediterranean (MedDiet) and Mediterranean-DASH intervention for neurodegenerative delay (MIND) diets, is associated with reduced AD risk and slower cognitive decline. However, the mechanistic pathways underpinning these associations remain incompletely understood, and evidence from randomized controlled trials has been less consistent. A critical but frequently overlooked distinction lies between mediators, defined as the biological mechanisms linking diet to AD outcomes, and moderators, which are individual or contextual factors that influence the magnitude and direction of these associations. Integrating mediators and moderators within a unified analytical framework is increasingly recognized as essential for advancing precision nutrition approaches to AD prevention (with multiple recent publications explicitly calling for this approach and providing empirical examples of its implementation). This mini-review, developed as the conceptual foundation for a planned meta-analysis, synthesizes current evidence on key mediating pathways, including neuroinflammation, brain insulin resistance, oxidative stress, blood-brain barrier dysfunction, hyperhomocysteinaemia, and gut-brain axis dysregulation. We further examine major moderating factors such as apolipoprotein E (APOE) ε4 genotype, biological sex, age, disease stage, and socioeconomic context that may determine who benefits from dietary interventions and under what conditions.},
}

@article {pmid42622814,
year = {2026},
author = {Elliott, L and Post, E and McClendon, A and Singer, J},
title = {The impact of psychosocial factors on neurocognitive functioning in family caregivers of persons with Alzheimer's disease and related dementias.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261476965},
doi = {10.1177/13872877261476965},
pmid = {42622814},
issn = {1875-8908},
abstract = {BackgroundLimited research has examined neurocognitive decline in family caregivers of persons with Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), despite most caregivers being over 65 and more susceptible to age-related declines due to increased stressors. The lack of insight into how psychosocial factors interact with caregivers' neurocognitive functioning limits our ability to identify targets for reducing neurocognitive risk.ObjectiveInvestigate the effects of psychosocial factors on neurocognitive functioning of AD/ADRD caregivers.MethodsThe caregiver sample (n = 42) consisted predominantly of older adults (Mage = 69.40, SDage = 11.58) who were caring for a spouse (64.3%). On average, caregivers provided 99 h of care per week for several years (M = 3.42, SD = 2.39). Multiple linear regressions were conducted to examine the effects of psychological (i.e., depression, anxiety, pre-death grief, perceived stress) and social (i.e., social support, social network) factors on caregivers' neurocognitive functioning (i.e., visuospatial memory, verbal memory, processing speed, intelligence, executive functioning).ResultsSocial support significantly predicted visuospatial memory and processing speed. As social support increased, delayed visuospatial memory and processing speed improved when controlling for social network size.ConclusionsCaregivers may face additional stressors and have limited time or opportunities for social engagement. Social support may be especially important for spousal caregivers losing a primary support source (i.e., spouse). Findings suggest social support is a potential intervention target for reducing caregivers' risk of neurocognitive decline.},
}

@article {pmid42622822,
year = {2026},
author = {Zhang, H and Lai, J and Wang, T and Li, T and Liu, S and Sun, DL and Chen, W and Kuang, W and Li, X and Zhang, M and Liao, Z and Xiang, X and Tuerxun, M and Zhang, X and Zhang, N and Xiao, S and Jessen, F and Yu, E and Yu, X and Wang, H},
title = {Adaptation and feasibility of the International Registry for Alzheimer's Disease and Other Dementias real-world datasets in old-age mental healthcare practice in China.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261478137},
doi = {10.1177/13872877261478137},
pmid = {42622822},
issn = {1875-8908},
abstract = {BackgroundAnti-amyloid disease-modifying therapies (DMTs) for early Alzheimer's disease (AD) are entering routine care, increasing the need for harmonized, registry-ready real-world data. The International Registry for Alzheimer's Disease and Other Dementias (InRAD) proposed a minimum dataset (MDS) and extended dataset (EDS), but their applicability to psychiatry-led old age mental healthcare practices in China is uncertain.ObjectiveTo adapt the InRAD dataset for real-world AD DMT practice across multiple psychiatry institutions in China and assess the feasibility of routine data capture for the proposed MDS/EDS.MethodsWe conducted a modified Delphi consensus study and a multicenter feasibility survey. Forty-nine experts classified domains/items into the MDS or EDS using predefined agreement thresholds. Thirty-five DMT-initiating mental healthcare teams reported the routine availability of the proposed data elements.ResultsHighly consistent with InRAD, ten domains were included in the China-adapted MDS/EDS, covering patient profiles and lifestyle, diagnostic work-up and biomarkers, treatment, outcomes, safety, treatment-monitoring examinations, and registry discontinuation. However, item prioritization reflected local practice, emphasizing diagnostic traceability, functional and neuropsychiatric outcomes, caregiver burden, and structured safety capture. Feasibility results revealed that many MDS elements were collected, but the consensus-defined MDS exceeded what is currently captured in a standardized, analysis-ready format; most EDS items were moderately feasible, while WHO-5 (patient version) and DAT-scan were least feasible.ConclusionsAn InRAD-aligned dataset is broadly acceptable for psychiatry-led AD DMT practices in China, but implementation gaps remain. A phased registry approach with standardized definitions and workflow-supported capture may improve the completeness and comparability of real-world DMT evidence.},
}

@article {pmid42622974,
year = {2026},
author = {Talebi, A and Nabili, S and Alaei, M and Koohsarian, P and Doostmohammadi, A and Dadashpour, M},
title = {Exosome-derived biomarkers as non-invasive tools in stroke, Parkinson's disease, and Alzheimer's disease.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42622974},
issn = {1573-7365},
mesh = {Humans ; *Exosomes/metabolism ; Biomarkers/metabolism ; *Alzheimer Disease/metabolism/diagnosis ; *Parkinson Disease/metabolism/diagnosis ; *Stroke/metabolism/diagnosis ; Animals ; MicroRNAs/metabolism ; },
abstract = {Neurological disorders, including stroke, Parkinson's disease (PD), and Alzheimer's disease (AD), are among the most prevalent and debilitating neuropathological conditions, affecting over 50 million people globally. Effective prevention and treatment strategies require a comprehensive understanding of reliable and disease-specific biomarkers. Such insights can enhance diagnostic precision, enable early detection, and support the development of targeted therapeutic approaches. In this review, we focus on exosome-derived proteins and small non-coding RNAs as promising non-invasive biomarkers for stroke, PD, and AD, given the accessibility and stability of exosomes in biological fluids. Furthermore, we examine their potential diagnostic and therapeutic relevance, emphasizing their functional roles, specificity, and sensitivity. Finally, we discuss current limitations, emerging challenges, and future research directions to guide the advancement of exosome-based biomarker discovery and clinical translation in neurological disorders. However, we emphasize that the comparative effectiveness of exosomal microRNAs (miRNAs) versus protein biomarkers requires direct validation in future head‑to‑head cohort studies.},
}

Humans
*Exosomes/metabolism
Biomarkers/metabolism
*Alzheimer Disease/metabolism/diagnosis
*Parkinson Disease/metabolism/diagnosis
*Stroke/metabolism/diagnosis
Animals
MicroRNAs/metabolism

@article {pmid42623026,
year = {2026},
author = {Yılmaz, F and Menteşe, E and Eyüpoğlu, OE and Kahveci, B and Emirik, M},
title = {Design, Synthesis, and Biological Evaluation of Benzimidazol-2-One Hybrids as Potential Anti-Alzheimer's Disease Agents.},
journal = {Drug development research},
volume = {87},
number = {6},
pages = {e70369},
pmid = {42623026},
issn = {1098-2299},
support = {FDK-2018-951//Recep Tayyip Erdogan Üniversitesi/ ; },
mesh = {*Alzheimer Disease/drug therapy ; *Cholinesterase Inhibitors/pharmacology/chemistry/chemical synthesis ; *Benzimidazoles/chemistry/pharmacology/chemical synthesis ; Drug Design ; *Monoamine Oxidase Inhibitors/pharmacology/chemistry/chemical synthesis ; Butyrylcholinesterase/metabolism ; Humans ; Antioxidants/pharmacology/chemistry/chemical synthesis ; Acetylcholinesterase/metabolism ; Monoamine Oxidase/metabolism ; Structure-Activity Relationship ; Animals ; Molecular Docking Simulation ; Coumarins/chemistry ; },
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder for which single-target therapies often provide insufficient benefit, motivating the development of multi-target-directed ligands (MTDLs). In this study, a novel series of benzimidazolone-based hybrids incorporating piperazine, coumarin, and triazole moieties was designed, synthesized, and evaluated for inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and monoamine oxidase-B (MAO-B), as well as antioxidant potential via on-line HPLC-based assays. Structures were confirmed by [1]H-NMR, [13]C-NMR (APT), and elemental analysis. Several compounds showed notable, micromolar-range inhibitory activity, though less potent than the reference drugs. Kinetic analysis showed that the leading compounds inhibited their respective enzymes via a mixed-type mechanism. Compound 1 showed the strongest AChE inhibition (IC50 = 0.777 ± 0.014 µM), compound 9b the highest BChE inhibition (IC50 = 0.659 ± 0.005 µM), and compound 9c the most potent MAO-B inhibition (IC50 = 2.431 ± 0.003 µM). Compound 8a showed the highest CUPRAC copper-reducing capacity, while 7c displayed the strongest DPPH radical-scavenging activity. Liposomal formulations of 4c, 7c, and 8a exhibited enhanced antioxidant responses relative to their free forms. In silico ADME predictions (SwissADME) indicated favorable drug-likeness and blood-brain barrier permeation for the compact scaffold (compound 1) and the piperazine-based hybrids, whereas the larger bis-conjugated derivatives were limited by high polarity and molecular weight. Overall, these benzimidazolone-based hybrids represent promising multi-target candidates for AD drug development.},
}

*Alzheimer Disease/drug therapy
*Cholinesterase Inhibitors/pharmacology/chemistry/chemical synthesis
*Benzimidazoles/chemistry/pharmacology/chemical synthesis
Drug Design
*Monoamine Oxidase Inhibitors/pharmacology/chemistry/chemical synthesis
Butyrylcholinesterase/metabolism
Humans
Antioxidants/pharmacology/chemistry/chemical synthesis
Acetylcholinesterase/metabolism
Monoamine Oxidase/metabolism
Structure-Activity Relationship
Animals
Molecular Docking Simulation
Coumarins/chemistry

@article {pmid42623143,
year = {2026},
author = {Chen, Y and Ge, L and Lazarovici, P and Zheng, W},
title = {Artemisinin Attenuates Aβ1-42 Aggregation via the CaMK IV/PKA-CREB-Ace-H4 Cascade in Neuronal Cultures and 3xTg-AD Models.},
journal = {The American journal of Chinese medicine},
volume = {},
number = {},
pages = {1-23},
doi = {10.1142/S0192415X26500667},
pmid = {42623143},
issn = {1793-6853},
abstract = {Alzheimer's disease (AD), a progressive neurodegenerative disease with a rising global prevalence, is characterized by amyloid-β (Aβ) aggregation, tau hyperphosphorylation, inflammation, oxidative damage, and neuronal apoptosis. Studies have increasingly recognized epigenetic modifications as key regulators in the development of AD. Epigenetic modifications, particularly histone acetylation, are increasingly recognized as critical regulators of cell survival and AD pathogenesis. Although artemisinin (ART) exhibits potent anti-oxidative, anti-inflammatory, and neuroprotective properties, its impact on histone acetylation in AD remains uncharacterized. This study investigated whether ART regulates histone acetylation to confer neuroprotection and rescue behavioral deficits in Alzheimer's disease models. Using SH-SY5Y cells, primary neurons, and 3xTg-AD mice, we found that ART restores histone acetylation homeostasis by enhancing histone H4 acetylation. Mechanistically, this effect is driven by the activation of the CaMK IV/PKA-CREB signaling cascade. Treatment with ART reduced ROS, improved mitochondrial function, decreased Aβ1-42 deposition, and suppressed neuronal apoptosis. However, these beneficial effects were abolished by PKA or CaMK IV inhibitors. Consequently, ART treatment significantly reduced reactive oxygen species (ROS) generation, restored mitochondrial function, decreased Aβ1-42 deposition, suppressed neuronal apoptosis, and alleviated AD-like neuropathology and cognitive deficits. Crucially, the neuroprotective and epigenetic benefits of ART were entirely abolished by pharmacological inhibitors of PKA or CaMK IV. This study is the first to demonstrate that artemisinin ameliorates AD pathology and behavioral impairments via the CaMK IV/PKA-CREB-Ace-H4 axis, establishing ART as a promising therapeutic candidate for epigenetic intervention in AD.},
}