@article {pmid37021420,
year = {2024},
author = {Suganya, A and Aarthy, SL},
title = {Application of Deep Learning in the Diagnosis of Alzheimer's and Parkinson's Disease: A Review.},
journal = {Current medical imaging},
volume = {20},
number = {},
pages = {e280323215043},
doi = {10.2174/1573405620666230328113721},
pmid = {37021420},
issn = {1573-4056},
mesh = {Humans ; *Deep Learning ; *Parkinson Disease/diagnostic imaging ; *Alzheimer Disease/diagnostic imaging ; Magnetic Resonance Imaging ; Early Diagnosis ; *Image Interpretation, Computer-Assisted/methods ; },
abstract = {Most neurodegenerative diseases such as Alzheimer's and Parkinson's are life-threatening, critical, and incurable affecting mainly the elderly population. Early diagnosis is challenging as disease phenotype is very crucial for predicting, preventing the progression, and effective drug discovery. In the last few years, Deep learning (DL) based neural networks are the state-of-the-art models deployed in industries and academics across different areas like natural language processing, image analysis, speech recognition, audio classification, and many more It has been slowly realized that they have a high potential in medical image analysis and diagnostics and medical management in general. As this field is vast and expanding rapidly, we have put focused on existing DL-based models to detect Alzheimer's and Parkinson's in particular. This study gives a summary of related medical examinations for these diseases. Frameworks and applications of many deep learning models have been discussed. We have given precise notes on pre-processing techniques used by various studies for MRI image analysis. An overview of the application of DLbased models in different stages of medical image analysis has been conferred. It has been realized from the review that more studies are focused on Alzheimer's compared to Parkinson's disease Additionally, we have tabulated the various public datasets available for these diseases. We have highlighted the potential use of a novel biomarker for the early diagnosis of these disorders. Also, some challenges and issues in implementing deep learning techniques for the detection of these diseases have been addressed. Finally, We concluded with some future research directions regarding deep learning techniques for diagnosis of the above diseases.},
}

Humans
*Deep Learning
*Parkinson Disease/diagnostic imaging
*Alzheimer Disease/diagnostic imaging
Magnetic Resonance Imaging
Early Diagnosis
*Image Interpretation, Computer-Assisted/methods

@article {pmid42800367,
year = {2026},
author = {Shen, S and Zhou, Y and Qian, J and Li, T and Hu, X and Ji, X and Zhang, X and Zhou, D},
title = {An intestine-centric view of neurodegeneration: How intestine-derived signals mediate the intestine-brain axis to impact Alzheimer's disease.},
journal = {Journal of neuroimmunology},
volume = {421},
number = {},
pages = {579102},
doi = {10.1016/j.jneuroim.2026.579102},
pmid = {42800367},
issn = {1872-8421},
abstract = {Alzheimer's disease (AD) has emerged as an increasingly prevalent and burdensome public health challenge with global aging, underscoring the urgent need to clarify the key factors involved in its pathogenesis for effective prevention and management. Mounting evidence suggests that disrupted crosstalk between the intestine and brain may contribute to aging-related neurodegeneration, including AD. Acting as a peripheral modulatory hub of the intestine-brain axis, the intestine releases a variety of bioactive substances that regulate brain function. This narrative review synthesizes current evidence on intestine-derived signaling molecules and immune mediators implicated in AD pathogenesis, with a focus on two primary communication routes: the vagus nerve and systemic circulation. In addition, intestine-targeted interventions-including dietary modification, probiotic supplementation, and fecal microbiota transplantation-are summarized. Notably, metagenomics-based intestinal microbiota aging clocks represent an emerging non-invasive strategy for AD risk prediction. Although preclinical findings are encouraging, the translational limitations and heterogeneity of current intestine-brain research remain noteworthy. In summary, this narrative review integrates substantial evidence on the correlation between intestine-derived mediators and AD and provides potential insights for the development of intestine-targeted preventive strategies.},
}

@article {pmid42800428,
year = {2026},
author = {Ott, LR and Hermann, W and Köhling, R and Storch, A and Teipel, SJ and Kirschstein, T},
title = {Comparison of amyloid-β, total tau and phospho-tau in clinical AD patients with and without epileptiform EEG patterns.},
journal = {Epilepsy research},
volume = {228},
number = {},
pages = {107921},
doi = {10.1016/j.eplepsyres.2026.107921},
pmid = {42800428},
issn = {1872-6844},
abstract = {BACKGROUND: Epilepsy is a relevant comorbidity of dementia due to Alzheimer's Disease (AD) and probably directly related to its pathology. We aimed to generate hypotheses how interictal epileptiform discharges (IEDs) may be associated with pathological levels of AD markers from cerebrospinal fluid (CSF).

OBJECTIVE: To perform bivariate analyses between IEDs or EEG background slowing to CSF AD markers including amyloid-β42 to amyloid-β40 ratio (Aβ ratio), total tau and phospho-tau.

METHODS: In this retrospective cross-sectional study, we identified 26 clinical AD patients who presented with at least one of three pathological neurodegeneration markers in the CSF (Aβ ratio ≤0.5, total tau ≥370 pg/ml, phospho-tau ≥66 pg/ml) and received at least one routine EEG.

RESULTS: IEDs and EEG background slowing were present in 5/26 and 14/26 patients, respectively. We observed that patients with IEDs or EEG background slowing had significantly lower phospho-tau levels than patients without (Cohen's d=0.91, P = 0.044 and Cohen's d=1.33, P = 0.005, respectively). Consistent with this, a positive history of seizures tended to be associated with lower phospho-tau levels (Cohen's d=0.79, P = 0.059). Moreover, phospho-tau levels were significantly correlated to dominant posterior EEG frequencies (Spearman's ρ=0.524, P = 0.006), and Aβ ratios were significantly lower in patients with normal EEG background frequencies than in those with EEG slowing (Cohen's d=1.31, P = 0.017).

CONCLUSIONS: Our bivariate analyses revealed the unexpected observation that the presence of IEDs was associated with lower rather than higher phospho-tau levels in clinical AD patients. This finding awaits further confirmation in a larger cohort.},
}

@article {pmid42800626,
year = {2026},
author = {Kurihara, T and Aoyagi, R and Kitase, S and Kuroda, S and Kaneko, M and Miura, T},
title = {Activation of Cu(II)-reducing ability of monoamine neurotransmitters triggered by amyloid-β fibrillization.},
journal = {Archives of biochemistry and biophysics},
volume = {},
number = {},
pages = {111013},
doi = {10.1016/j.abb.2026.111013},
pmid = {42800626},
issn = {1096-0384},
abstract = {The reduction of Cu(II) to Cu(I) in oxidative extracellular environments contributes to oxidative stress because the reoxidation of Cu(I) back to Cu(II) generates reactive oxygen species. Monoamine neurotransmitters such as serotonin (5-HT) and dopamine (DA) possess Cu(II)-reducing ability and coexist with copper ions near the synapse, suggesting that they may serve as potential mediators of oxidative stress. The neurotoxicity of aggregated amyloid-β peptide (Aβ) observed in the brains of Alzheimer's disease patients is thought to arise from oxidative stress induced by complex formation of Aβ with redox-active metal ions. However, the absence of apparent Cu(II)-reducing activity in Aβ suggests the involvement of other reducing agents in the generation of oxidative stress. In this study, we examined the effects of Aβ on the redox reactions between copper and monoamine neurotransmitters 5-HT and DA. The Cu(II)-reducing activities of both neurotransmitters, together with the accompanying production of hydrogen peroxide, were inhibited by either unfibrillized Aβ1-40 or non-amyloidogenic Aβ1-16, whereas fibrillized Aβ1-40 enhanced them. Canonical small-molecule Cu(II) ligands, such as L-histidine, diminished these activities, whereas Cu(I) chelators exerted an enhancing effect. These findings suggest that the activation of monoamine-mediated copper reduction by fibrillized Aβ1-40 may be attributable to the Cu(I)-binding capability that is absent in the monomeric form. This study provides a partial mechanistic basis for the causal link between Aβ aggregation and the onset of Alzheimer's disease.},
}

@article {pmid42800647,
year = {2026},
author = {Ranxhi, B and LeWitt, PA and Tsou, WL and Todi, SV},
title = {Polyamines across neurodegenerative proteinopathies.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107629},
doi = {10.1016/j.nbd.2026.107629},
pmid = {42800647},
issn = {1095-953X},
abstract = {Polyamines (PAs) are evolutionarily conserved metabolites that connect protein quality control with lysosomal, mitochondrial, and redox homeostasis. Their metabolism is situated at a critical intersection of cell-sustaining and neurodegenerative pathways. Here, we synthesize evidence across Alzheimer's disease, Parkinson's disease, polyglutamine repeat disorders, amyotrophic lateral sclerosis, and multiple system atrophy, each of which differ in vulnerability to changes in PA metabolism. Although previous reviews have investigated polyamines in individual neurodegenerative disorders, few have compared their roles across the broader spectrum of neurodegenerative proteinopathies. Here, we address this gap by synthesizing evidence across multiple diseases to examine how PAs influence disease-associated protein aggregation and clearance, and how these effects depend on PA species, concentration, cellular context, disease stage, subcellular localization, redox state, and lysosomal and mitochondrial capacity. Human tissue and biofluid studies report disease-associated changes in PA metabolites, pathway enzymes, and transporter remodeling, as a function of neurodegenerative disorders. Mechanistic studies reveal that spermidine and spermine can alter the assembly, condensation, compartmentalization, and clearance of various neurotoxic proteins, whereas the effects of putrescine are more system- and concentration-dependent. These effects engage both shared pathways and distinct mechanisms, depending on protein identity, cell type, and subcellular location. Curiously, PA manipulation may be protective in one context yet harmful in another. The framework that we propose can distinguish adaptive remodeling from pathogenic dysregulation and can guide disease-relevant therapeutic strategies.},
}

@article {pmid42800673,
year = {2026},
author = {de Leve, SJ and Wang, X and Alavifard, H and Dara, L and DeLeve, LD},
title = {Reversing liver sinusoidal endothelial aging restores clearance of amyloid-beta and LDL.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113608},
doi = {10.1016/j.jbc.2026.113608},
pmid = {42800673},
issn = {1083-351X},
abstract = {In healthy liver, large macromolecules pass freely into the space of Disse through liver sinusoidal endothelial cell (LSEC) fenestration. In aging, LSEC fenestration is largely lost (pseudocapillarization). We hypothesized that restoring aged LSECs' fenestration would enhance passage into the space of Disse of large-diameter (>50 nm) triglyceride-rich lipoproteins to which the majority of circulating amyloid-beta is bound and permit hepatocyte uptake of amyloid-beta: in aged rats, two weeks of the soluble guanylate cyclase activator cinaciguat restored fenestration; circulating amyloid-beta 40 levels halved, returning to levels found in young rats. Surprisingly, cinaciguat also reversed age-related increases in LDL (a smaller, 20-30 nm diameter lipoprotein), which crosses the sinusoidal endothelial barrier even when LSECs are defenestrated. We therefore investigated additional mechanisms by which LSECs promote hepatocyte clearance. Whereas primary hepatocytes had minimal uptake of amyloid-beta 40 or LDL, hepatocytes cultured in young rat LSEC conditioned medium retained their uptake function. Aged rat LSEC conditioned medium did not facilitate hepatocyte amyloid-beta 40 and LDL uptake but treating aged rats with cinaciguat restored aged rat LSECs paracrine signaling. We discovered that heparin-binding epidermal growth factor-like growth factor (HB-EGF) mediates this LSEC-hepatocyte interaction and that HB-EGF is synthesized but not secreted by aged rat LSECs; cinaciguat treatment restores aged LSECs' HB-EGF secretion. Treatment reversed age-associated loss of LDLR and LRP1 surface expression in rat hepatocytes. This study identifies a candidate therapy to address age-related increases in circulating amyloid-beta and LDL and elucidates an intercellular crosstalk mechanism that governs these phenomena.},
}

@article {pmid42800791,
year = {2026},
author = {Wang, Y and Li, B and Liang, Y and Carlson, M and DiGiacomo, P and Moein Taghavi, H and Maclaren, J and Bell, M and Pham, N and Decker, JH and Lv, M and Liang, T and Wong, J and Mormino, E and Henderson, VW and Zaharchuk, G and Rutt, B and Shao, W and Georgiadis, M and Zeineh, M},
title = {Accelerating 7T Gradient-Echo Brain MRI With Generative AI Denoising.},
journal = {Academic radiology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.acra.2026.09.011},
pmid = {42800791},
issn = {1878-4046},
abstract = {RATIONALE AND OBJECTIVES: This study aimed to efficiently denoise short 7 T MRI acquisitions to achieve the image quality of longer scans using a generative Artificial Intelligence (AI) model.

MATERIALS AND METHODS: A 7T Conditional Diffusion Model (7TCDM) was trained on an in-house 7T dataset of 11 examinations consisting of multi-repetition 2D T2-weighted gradient-echo acquisitions. The model utilized native single-acquisition 2D reconstructions, using multi-repetition images as a reference to guide denoising and enhance signal-to-noise ratio and contrast. Performance was compared to the same single-acquisition reconstruction either unprocessed or enhanced by a similarly trained convolutional neural network, vision transformer, and generative adversarial network, using Mean Squared Error (MSE), Peak Signal-to-Noise Ratio (PSNR), Structural Similarity Index Measure (SSIM), and comprehensive neuroradiologic ratings.

RESULTS: 7TCDM was tested on 2D T2-weighted gradient-echo images from 19 participants: eight healthy controls, six individuals with mild cognitive impairment, and five with Alzheimer's disease. Referencing the multi-repetition reference standard, 7TCDM improved the single-acquisition original image by 31.7% in MSE, 4.9% in PSNR, and 7.5% in SSIM, outperforming all other models in all metrics (P < 0.001). Expert rater evaluations confirmed superior image quality, with significantly enhanced detail (P < 0.001) and contrast preservation (P < 0.001) for the hippocampi, for white matter lesions, and for small cortical veins.

CONCLUSIONS: Generative AI denoising provides high-quality denoised images from shorter scans, increasing the feasibility of scanning patients in shorter times while preserving essential anatomical and pathological details.},
}

@article {pmid42800819,
year = {2026},
author = {Okada, JJB and Yang, MS and Yu, RA and Du, L and Theng, B and Shen, G and Lee, WC},
title = {What Increases the Likelihood of Dementia Among Asian Americans? Analysis of Nativity and Life Course Factors.},
journal = {Journal of racial and ethnic health disparities},
volume = {},
number = {},
pages = {},
pmid = {42800819},
issn = {2196-8837},
abstract = {OBJECTIVES: The Alzheimer's Association has reported a 746% increase in dementia-related deaths in Asian American populations between 2000 and 2018, the most significant rise compared to all other racial groups. Asian Americans face a unique myriad of obstacles and factors contributing to significant health disparities, including those in dementia. Our aim is to compare determinants and outcomes of dementia between US-born and foreign-born Asian Americans.

METHODS: Data from the 2019-2022 National Health Interview Survey was analyzed to examine the relationship between nativity and dementia. Other life course risk factors and outcomes of having dementia were also included in the analysis. The study sample included 16,331 US-born and 126,978 foreign-born Asian Americans.

RESULTS: Foreign-born Asian Americans were found to have a higher proportion of dementia compared to US-born Asian Americans (1.1%>0.4%, p = 0.0140). Risk factors that were found to significantly explain the relationship between nativity and dementia included age > 65, ever being married, having some college education, and having Medicaid coverage. Foreign-born Asian Americans with dementia are more likely to suffer from depression (p < 0.001) and experience/have difficulty in social involvement (p < 0.001) compared to US-born Asian Americans with dementia.

CONCLUSION: Our findings reaffirm that nativity contributes to the heterogeneous risk and outcomes of dementia in Asian Americans and the likelihood of having dementia is further impacted by life course factors. Interventions to support Asian American immigrants are needed to reduce the burden of dementia. More studies that identify nativity variations are also recommended to address health disparities that disproportionately affect older immigrants.},
}

@article {pmid42800866,
year = {2026},
author = {Gaetani, L and Bellomo, G and Chiasserini, D and De Rocker, C and Goossens, J and Paoletti, FP and Vanmechelen, E and Parnetti, L},
title = {Correction: Influence of co-pathology on CSF and plasma synaptic markers SNAP25 and VAMP2 in Alzheimer's disease and Parkinson's disease.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {42800866},
issn = {1758-9193},
}

@article {pmid42800954,
year = {2026},
author = {Kang, G and Oldham, MC},
title = {Coordinated dysregulation of modular gene activity in human neuropathologies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.08.25.747130},
pmid = {42800954},
issn = {2692-8205},
abstract = {Understanding which genes are reproducibly dysregulated in which cell types is foundational knowledge for efforts to slow or reverse pathologies. For neuropathologies, such efforts rely primarily on differential expression analysis of single-nucleus RNA-seq (snRNA-seq) data. However, this strategy suffers from experimental and statistical challenges that limit marker gene reproducibility. We describe a novel strategy called Covariation Projection Analysis (CoPA) that combines the power of bulk sampling with the precision of single-cell methods. By 'projecting' bulk gene coexpression modules onto pseudobulked snRNA-seq cell types, CoPA reveals the cellular origins of highly reproducible genomic programs and their relative importance among cell types. By comparing CoPA projection patterns between normal and pathological human brain samples using d ifferential CoPA (dCoPA), we identify gene coexpression modules that are uniformly and reproducibly dysregulated in specific neocortical cell types in Alzheimer's disease or schizophrenia. We share our findings through a novel web application called CoPA Cabana (https://oldhamlab.shinyapps.io/copacabana/).},
}

@article {pmid42801050,
year = {2026},
author = {Youn, BY and Park, S and Song, D and Nam, KC},
title = {Digital twin for neurological conditions: a systematic scoping review.},
journal = {Biomedical engineering letters},
volume = {16},
number = {5},
pages = {1219-1242},
pmid = {42801050},
issn = {2093-985X},
abstract = {Digital twin technology has emerged as a promising approach for advancing precision medicine in complex diseases, particularly in neurology. This scoping review aimed to systematically map the current literature on digital twin applications in neurological conditions, focusing on study characteristics, modeling approaches, data sources, and clinical applications. A comprehensive search across six databases from inception to February 2026 identified 36 studies that met the inclusion criteria. The findings demonstrated a rapid increase in publications since 2023, with Alzheimer's disease (n = 14) and stroke (n = 12) representing the most frequently studied conditions. Data-driven and machine learning-based models were the most common approaches, followed by mechanistic and hybrid models. Major application domains included clinical trial optimization, disease progression modeling, risk prediction, and personalized treatment. However, most studies were proof-of-concept or retrospective in design, with limited external validation and no randomized controlled trials identified. Additionally, many models lacked continuous real-time data integration, indicating that few met the criteria of fully dynamic digital twins. These findings suggest that while digital twins hold substantial potential to transform precision neurology, significant challenges remain in terms of methodological rigor, standardization, and clinical translation. Future research should prioritize prospective validation, integration of multimodal real-world data, and the development of standardized frameworks to support safe and effective implementation.},
}

@article {pmid42801132,
year = {2026},
author = {Mudaranthakam, DP and Yoksh, L and Makovec, A and Ratnayake, I and Pepper, S and Lewandowski, T and Vidoni, ED and Burns, JM},
title = {Financial Toxicity and Multidimensional Economic Strain Among Dementia Caregivers.},
journal = {Alzheimer's & dementia. Behavior & socioeconomics of aging},
volume = {2},
number = {3},
pages = {},
pmid = {42801132},
issn = {2997-3805},
support = {P30 AG072973/AG/NIA NIH HHS/United States ; },
abstract = {INTRODUCTION: Financial toxicity is an underrecognized but significant burden among caregivers of individuals with Alzheimer's disease and related dementias (ADRD). The interaction between economic hardship, caregiver burden, and social determinants of health (SDOH) remains poorly defined.

METHODS: We conducted a cross-sectional survey of 79 ADRD caregivers recruited through the University of Kansas Alzheimer's Disease Research Center. Participants completed the COST measure, Zarit Burden, Resource Utilization in dementia questionnaire, and an SDOH assessment. The primary outcome was moderate-to-severe financial toxicity (COST ≤26).

RESULTS: Financial toxicity affected 50.6% of caregivers. After adjusting for caregiver age and household income, higher caregiver burden was associated with greater financial toxicity (OR = 1.12), while older age was associated with lower odds of financial toxicity (OR = 0.93), and low household income was associated with greater financial toxicity compared with high income households (OR = 7.63).

DISCUSSION: Financial toxicity is common among ADRD caregivers and closely linked to burden and socioeconomic disadvantages, underscoring the need for policy and support interventions.},
}

@article {pmid42801166,
year = {2026},
author = {Wang, Y and Cai, J and Kong, X and Li, J and Ge, Y and Zhang, Y and Chen, Y and Zhu, M and Gong, H and Zhao, D and Pi, J},
title = {Promising Roles of Selenium Nanoparticles in Anti-Tuberculosis Therapy: Opportunities and Challenges.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {627381},
pmid = {42801166},
issn = {1178-2013},
mesh = {*Selenium/chemistry/pharmacology/administration & dosage ; Humans ; Animals ; *Tuberculosis/drug therapy ; *Antitubercular Agents/chemistry/pharmacology/administration & dosage ; *Nanoparticles/chemistry ; Mycobacterium tuberculosis/drug effects ; },
abstract = {Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the most threatening infectious disease worldwide. Selenium, an essential micronutrient, is incorporated into selenoproteins such as glutathione peroxidase, which modulate lipid peroxidation and immune responses, thus playing pivotal roles in host defense against infection and control of Mtb dissemination. As an emerging class of selenium-based medicines, selenium nanoparticles (SeNPs) have demonstrated attractive anti-tuberculosis potential based on their favorable bioactivity, lower toxicity compared, high drug-loading capacity, sustained-release kinetics, and enhanced targeting specificity. Beyond their anti-TB potential, SeNPs have shown significant promise in various biomedical applications, including the treatment of diabetes, liver disease, Alzheimer's disease, and cancer, owing to their ability to modulate oxidative stress, inflammation, and apoptotic pathways. This review explores the relationship between selenium and the occurrence and development of tuberculosis, evaluates the potential of serum selenium as an auxiliary diagnostic biomarker, and outlines common preparation methods for SeNPs, including physical, chemical, and biological synthesis approaches. Furthermore, this review systematically summarizes the anti-tuberculosis functions of SeNPs, detailing multiple mechanisms such as accelerating Mtb-lysosome fusion, modulating intracellular ROS levels, driving M1 macrophage polarization, and inhibiting the PI3K/AKT/mTOR signaling pathway to collectively trigger autophagy and apoptosis in Mtb-infected macrophages. These insights may support the development of new anti-tuberculosis technologies based on SeNPs. Furthermore, we also address the key challenges hindering the clinical translation of SeNPs: the long-term in vivo tissue accumulation patterns of SeNPs have not been fully elucidated, long-term systemic nanotoxicity data remain scarce, almost all anti-tuberculosis studies are restricted to in vitro cell experiments and animal models, and the translational pathway from laboratory studies to clinical practice remains ambiguous.},
}

*Selenium/chemistry/pharmacology/administration & dosage
Humans
Animals
*Tuberculosis/drug therapy
*Antitubercular Agents/chemistry/pharmacology/administration & dosage
*Nanoparticles/chemistry
Mycobacterium tuberculosis/drug effects

@article {pmid42801200,
year = {2026},
author = {Liu, R and Yue, H and Li, X and Sun, W and Yang, J},
title = {The Versatile Roles of Exosomes in Neurodegenerative Disorders: From Pathological Mechanism and Diagnostic Biomarkers to Therapeutic Application.},
journal = {Drug design, development and therapy},
volume = {20},
number = {},
pages = {631482},
pmid = {42801200},
issn = {1177-8881},
mesh = {Humans ; *Exosomes/metabolism/pathology ; *Neurodegenerative Diseases/diagnosis/drug therapy/metabolism/pathology/therapy ; Biomarkers/metabolism/analysis ; Animals ; },
abstract = {Neurodegenerative diseases are characterized by cognitive or motor impairments resulting from the progressive degeneration of neurons or myelin sheaths. Currently, the majority of these disorders remain incurable, leading to significant detriments in patients' quality of life and imposing substantial economic burdens. Exosomes are a type of extracellular vesicles secreted by cells into the extracellular space, typically range from 30 to 150 nanometers in diameter. These vesicles have been identified in a variety of cell types and can participate in various physiological and pathological processes, including intercellular transport of biomolecules, signal transduction, immune modulation, tissue repair, facilitation of tumor metastasis, and evasion of immune surveillance by cancer cells. In recent years, the potential applications of exosomes in neurodegenerative diseases have garnered increasing attention. Their roles encompass early diagnostic biomarker functions, vehicles for drug delivery and therapeutic agents, mediators in the propagation of pathogenic proteins, and regulators of neuroinflammatory responses. In this review, we try to aims to synthesize recent progress in exosome isolation techniques, elucidate the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), and examine the diagnostic and therapeutic applications of exosomes within these conditions. Furthermore, it addresses current limitations in exosome-based applications and explores potential strategies to overcome these challenges. The insights of this review may provide the research directions and guidance for future related researchers in these fields.},
}

Humans
*Exosomes/metabolism/pathology
*Neurodegenerative Diseases/diagnosis/drug therapy/metabolism/pathology/therapy
Biomarkers/metabolism/analysis
Animals

@article {pmid42801246,
year = {2026},
author = {Zrineh, A and Akwan, R and Darawsheh, R and Nasser, A and Elsharkawy, MM},
title = {Alzheimer's Disease: From Molecular Pathogenesis to Disease-Modifying Therapies and Clinical Implementation in Aging Populations.},
journal = {Clinical interventions in aging},
volume = {21},
number = {},
pages = {639690},
pmid = {42801246},
issn = {1178-1998},
mesh = {Humans ; *Alzheimer Disease/drug therapy/genetics/physiopathology/therapy/diagnosis ; Amyloid beta-Peptides/metabolism ; *Aging ; Biomarkers ; Cholinesterase Inhibitors/therapeutic use ; Aged ; },
abstract = {Alzheimer's disease (AD) is the leading cause of dementia worldwide, disproportionately affecting individuals over 65 years of age and imposing a rapidly escalating burden on healthcare systems and caregivers globally. For decades, management relied on symptomatic agents-cholinesterase inhibitors and memantine-that provide modest cognitive benefits without altering disease progression. The recent approvals of the anti-amyloid monoclonal antibodies lecanemab (2023) and donanemab (2024) represent a paradigm shift, offering the first therapies that modestly but significantly slow clinical decline by targeting the underlying amyloid-β pathology. However, these advances are accompanied by important safety concerns, particularly amyloid-related imaging abnormalities, substantial costs, and unresolved questions regarding long-term clinical meaningfulness and equitable access. This comprehensive review synthesizes current knowledge across the full spectrum of AD, encompassing molecular pathophysiology (amyloid cascade, tau hyperphosphorylation, and neuroinflammation), genetic architecture (familial mutations and APOE-mediated risk), evolving biomarker-based diagnostic frameworks, established symptomatic treatments, and newly approved disease-modifying agents. We further examine emerging therapeutic strategies, including tau-targeted therapies, neuroinflammation-directed approaches, multi-target and combination strategies, drug delivery innovations, and prevention trials in preclinical populations. Throughout, we critically evaluate the evidence, acknowledging controversies and limitations while identifying promising future directions. Importantly, integrating these diagnostic and genetic advances into geriatric care settings presents unique implementation challenges, as aging populations often face comorbidities, polypharmacy, and limited access to specialized diagnostic infrastructure. As AD therapeutics enter a new era, integrating pharmacological interventions with biomarker-guided patient selection, rigorous safety monitoring, and modifiable risk factor management will be essential for optimizing outcomes in aging populations.},
}

Humans
*Alzheimer Disease/drug therapy/genetics/physiopathology/therapy/diagnosis
Amyloid beta-Peptides/metabolism
*Aging
Biomarkers
Cholinesterase Inhibitors/therapeutic use
Aged

@article {pmid42801273,
year = {2026},
author = {Ocampo-Mota, J and Padilla, D and Karlinsey Skidmore, B and Cardiel, E and Khanna, S and Pinto, M and Marquez, DX},
title = {Ojo 2-barriers and recommendations for the recruitment, retention, and implementation of remote physical activity interventions for older Latinos.},
journal = {Translational behavioral medicine},
volume = {16},
number = {1},
pages = {},
doi = {10.1093/tbm/ibag066},
pmid = {42801273},
issn = {1613-9860},
support = {//U.S. Department of Health and Human Services/ ; },
mesh = {Humans ; *Hispanic or Latino/psychology ; *Exercise/psychology ; Aged ; COVID-19/prevention & control ; Female ; *Health Promotion/methods ; Male ; SARS-CoV-2 ; Patient Selection ; },
abstract = {BACKGROUND: Older Latinos participate in low levels of physical activity (PA), despite it being a protective factor against chronic diseases, like Alzheimer's disease and related dementias . PA interventions, like the BAILAMOS™ dance program and ¡En Forma y Fuerte! (Fit & Strong!®) exercise program, were created to address a lack of culturally relevant PA programs for older Latinos. The COVID-19 pandemic allowed for these in-person PA interventions to be adapted for remote delivery. The Cognitive Enhancement and Risk-Reduction through Exercise for Brain-Related Outcomes study examined the feasibility and impact of BAILAMOS™ and ¡En Forma y Fuerte! delivered remotely to inactive older Latinos with memory concerns.

PURPOSE: The purpose of the present paper is to describe challenges in the implementation and delivery of remote PA-interventions for older Latino adults; and potential strategies to overcome those challenges.

METHODS: Barriers to implementation and delivery of BAILAMOS™ and ¡En Forma y Fuerte!, and strategies developed by the research team to overcome them, were documented by the research team as they arose. Challenges/strategies were grouped using the Theoretical Domains Framework.

RESULTS: A total of 38 participants were enrolled and randomized into either BAILAMOS™ or ¡En Forma y Fuerte!. Barriers were grouped into the following themes: (i) Environmental Context and Resources, (ii) Skill & Knowledge, and (iii) Social Influences.

CONCLUSIONS: The delivery of a remote PA-intervention to older Latino adults is possible, but researchers should consider barriers that they are likely to encounter. Our findings highlight the importance of technology orientation sessions, ongoing device assistance, flexible program schedules, and participant safety protocols. Additional recommendations include considering the cost of purchasing devices as participants might not already own one, and the time-investment needed for technology support and developing new safety protocols for remote delivery.

CLINICAL TRIAL INFORMATION: C.E.R.E.B.R.O.: NCT05588778 and Fit & Strong!: NCT03180008.},
}

Humans
*Hispanic or Latino/psychology
*Exercise/psychology
Aged
COVID-19/prevention & control
Female
*Health Promotion/methods
Male
SARS-CoV-2
Patient Selection

@article {pmid42801300,
year = {2026},
author = {Thomas, J and Subhashree, S and Mohanty, SN and V S, DP and Sanjesh, R and Jibrin Musa, M},
title = {Multidomain Electroencephalography Biomarker Fusion for Machine Learning-Based Dementia Classification.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {235},
pages = {},
doi = {10.3791/72549},
pmid = {42801300},
issn = {1940-087X},
mesh = {Humans ; *Electroencephalography/methods ; *Machine Learning ; Biomarkers/analysis ; *Dementia/classification/diagnosis ; Alzheimer Disease/diagnosis/classification ; Random Forest ; Classification Algorithms ; Female ; },
abstract = {Electroencephalography (EEG) has been investigated as a noninvasive approach for characterizing brain activity in neurodegenerative conditions. This study evaluated whether multidomain EEG biomarkers could distinguish Alzheimer's disease (AD), frontotemporal dementia (FTD), and healthy controls (HC). The publicly available dataset contained resting-state, eyes-closed EEG recordings from 88 participants, including 36 with AD, 23 with FTD, and 29 healthy controls. Multidomain EEG biomarkers and demographic features were extracted for machine learning classification. The EEG-derived features included root-mean-square (RMS), power spectral density (PSD), and entropy measures. A Random Forest classifier was trained using the combined feature set and interpreted using explainable artificial intelligence. Feature-stability and Cohen's d effect-size analyses were performed to evaluate feature contributions, followed by an ablation analysis. Entropy-based features showed the lowest contribution to classification. The complete multidomain model achieved 96% training accuracy and 92% test accuracy. After the removal of the entropy features, test accuracy increased to 94%. These results describe the classification performance of the selected multidomain EEG and demographic features within the Random Forest framework.},
}

Humans
*Electroencephalography/methods
*Machine Learning
Biomarkers/analysis
*Dementia/classification/diagnosis
Alzheimer Disease/diagnosis/classification
Random Forest
Classification Algorithms
Female

@article {pmid42801323,
year = {2026},
author = {Huang, Z and Wang, Y and Lowerison, MR and Xu, Y and Yi, M and Lin, BZ and Shin, Y and Sekaran, NVC and Llano, DA and Song, P},
title = {Longitudinal Awake Mouse Brain Imaging Using Functional Ultrasound and Functional Ultrasound Localization Microscopy.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e77931},
pmid = {42801323},
issn = {2198-3844},
support = {R21EB030072//National Institute of Biomedical Imaging and Bioengineering and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health/ ; R56NS131516//National Institute of Biomedical Imaging and Bioengineering and the National Institute of Neurological Disorders and Stroke of the National Institutes of Health/ ; 2523603//National Science Foundation CAREER/ ; //Chan Zuckerberg Initiative Ben Barres Early Career Award/ ; },
abstract = {Functional ultrasound (fUS), ultrasound localization microscopy (ULM), and functional ULM (fULM) are three emerging brain ultrasound imaging techniques that measure the cerebrovascular structure and function at different spatial scales. Here we establish an awake, longitudinal fUS-ULM-fULM imaging framework to study structural vascularity, microvascular flow velocity, mesoscale hemodynamic responses, and microvascular functional responses in the same animals across 5 months. No significant linear longitudinal trend was detected for any of the ultrasound measurements in control animals, with structural measures showing lower longitudinal variability than functional readouts. Mean flow velocity showed the strongest longitudinal consistency and the lowest pooled within-subject variability. Behavioral testing and GFAP/Iba1 staining further revealed no detectable memory impairment or chronic neuroinflammatory response during the 5-month serial imaging setup. Application of fUS-ULM-fULM in 5xFAD-positive mice revealed a temporally ordered, cross-scale pattern of cerebrovascular dysfunction, with cerebral blood flow velocity declining first followed by impaired stimulus-evoked responses at the microvascular and then mesoscale levels. No vascular structural changes were detected across 5 months. Overall, this study established a stable longitudinal multimodal ultrasound imaging framework for tracking the awake mouse brain and demonstrated the utility for detecting cerebrovascular structural and functional variations in a preclinical Alzheimer's disease mouse model.},
}

@article {pmid42801558,
year = {2026},
author = {Guo, R and Li, X and Zou, C and Zheng, C and Wu, X and Lu, X and Yan, J and Zhang, J and Luo, X and Ye, S and Zhou, D},
title = {Temporal-Targeted Accelerated 40 Hz tACS Enhances Cognitive Function and Network Integration in Alzheimer's Disease: A Randomized Clinical Trial.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e77851},
pmid = {42801558},
issn = {2198-3844},
support = {No.2024GYX41//Lishui Municipal Public Welfare Technology Application Research Program/ ; 2023S035//Ningbo Public Welfare Science and Technology Plan Project/ ; No.PPXK20182024-0708//Ningbo Medical and Health Brand Discipline/ ; No.2022L002//Ningbo Clinical Medical Research Centre for Mental Health/ ; No.2022030410//Ningbo Top Medical and Health Research Program/ ; },
abstract = {The temporal lobes are key hubs for memory and cognition. Although 40 Hz transcranial alternating current stimulation (tACS) has shown potential cognitive benefits, evidence for accelerated bilateral temporal stimulation remains limited. This study aims to evaluate its cognitive and neural effects. In this randomized, double-blind, controlled trial, 100 Alzheimer's disease (AD) patients were randomized 1:1 to active or sham 40 Hz tACS over the bilateral temporal. Cognitive outcomes at three time points were analyzed using mixed repeated-measures analysis of variance (ANOVA). Resting-state functional near-infrared spectroscopy (fNIRS) data from baseline and Week 4 were analyzed using ANOVA, followed by network-based statistics with family-wise error (FWE) correction. Eighty-five participants completed the trial. Significant Group × Time interactions were observed for Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) total (p = 0.010), memory (p = 0.007), and praxis (p = 0.002), but not for the Mini-Mental State Examination (MMSE) (p = 0.075). The fNIRS analysis revealed a functional network primarily involving the frontal and parietal regions, comprising 38 connections and 18 nodes (pFWE = 0.010). Active-group connectivity changes were associated with ADAS-Cog total, language, praxis, and MMSE variations, but not in the sham group. Accelerated bilateral temporal 40 Hz tACS improved cognition and modulated frontotemporoparietal connectivity. Larger multicenter studies with biomarkers are warranted.},
}

@article {pmid42801635,
year = {2026},
author = {Lee, R and Kim, G and Black, ER and Kim, S},
title = {Co-activation of Selective Nicotinic Acetylcholine Receptor Subtypes Is Required for Neuroprotection against Alzheimer's Disease.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e77858},
pmid = {42801635},
issn = {2198-3844},
support = {TR002535//Kim laboratory for their generous support. We appreciate Dr. Eunhye Park for the technical guidance and Dr. Don Rojas for support with data analysis. This work is supported by the NIH/NCATS Colorado CTSA Grant/ ; 1R03AG072102//Boettcher Foundation's Webb-Waring Biomedical Research Program, BrightFocus Foundation, and the NIH grant/ ; //Colorado State University College of Veterinary Medicine and Biomedical Sciences/ ; },
abstract = {Beta-amyloid peptide (Aβ)-induced suppression of hippocampal GABAergic interneuron activity drives hyperexcitability, amyloid pathology, and cognitive impairment in Alzheimer's disease (AD), suggesting that enhancing hippocampal inhibition may be protective. However, hippocampal interneurons are highly diverse and differentially regulate inhibition and cognition, making it challenging to identify the affected subtypes and optimally restore hippocampal inhibition in AD. We have previously found that Aβ selectively binds to two of the three major hippocampal nicotinic acetylcholine receptor (nAChR) subtypes, α7- and α4β2-nAChRs, but not α3β4-nAChRs, and inhibits these two receptors in hippocampal inhibitory interneurons to decrease their activity, leading to hyperexcitation in excitatory neurons. Here, we further reveal that α7- and α4β2-nAChRs predominantly control nicotinic cholinergic signaling and neuronal activity in hippocampal parvalbumin-positive (PV+) and somatostatin-positive (SST+) inhibitory interneurons, respectively. We also find that systemic co-stimulation of α7- and α4β2-nAChRs is required to reverse hippocampal hyperexcitability, dysfunction of fear learning-associated hippocampal oscillatory activity, and hippocampus-dependent memory loss, and to reduce Aβ pathology in AD model mice. This suggests that co-stimulation of PV+ and SST+ cells via activation of α7- and α4β2-nAChRs together is required to enhance hippocampal inhibition optimally, which reverses hippocampal dysfunction, reduces amyloid pathology, and ultimately prevents memory loss in AD.},
}

@article {pmid42801691,
year = {2026},
author = {Zhu, S and Han, X and Zhang, H and Ye, C and Xia, T and Gu, X},
title = {14-3-3γ Protects Against Postoperative Cognitive Dysfunction by Regulating Tau Thr205 Phosphorylation and Synaptic Integrity.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e77480},
pmid = {42801691},
issn = {2198-3844},
support = {ZDXK202232//Jiangsu Provincial Medical Key Discipline/ ; },
abstract = {BACKGROUND: 14-3-3γ is implicated in neurodegeneration, yet its role in postoperative cognitive dysfunction (POCD) remains unclear.

METHODS: We performed CSF proteomic profiling using the SomaScan 7K platform in the Alzheimer's Disease Neuroimaging Initiative cohort (n = 237) to identify biomarkers associated with neurodegeneration-enriched cognitive vulnerability (NECV). A prospective surgical cohort (n = 213) was used to evaluate circulating 14-3-3γ levels in relation to perioperative cognitive outcomes. Mechanistic studies were conducted using a murine surgery model, AAV-mediated gene manipulation, neuronal cultures, pharmacological intervention, and molecular dynamics simulations.

RESULTS: CSF proteomics identified 14-3-3γ as a candidate biomarker associated with NECV and neurodegenerative progression. Plasma 14-3-3γ levels were associated with POCD and postoperative delirium. In mice, anesthesia and surgery reduced hippocampal 14-3-3γ expression, accompanied by increased Tau phosphorylation at Thr205 among examined sites, synaptic dysfunction, and cognitive impairment. Neuronal 14-3-3γ overexpression rescued these deficits. Mechanistically, 14-3-3γ interacted with Tau in a phosphorylation-dependent manner and regulated Tau phosphorylation homeostasis. Pharmacological stabilization of the 14-3-3γ-Tau interaction using FC-A reduced Tau Thr205 phosphorylation and improved cognition, whereas TauT205E expression diminished this rescue effect.

CONCLUSIONS: 14-3-3γ represents a potential regulator of postoperative cognitive vulnerability and a candidate therapeutic target for POCD.},
}

@article {pmid42801851,
year = {2026},
author = {Abramson, CM and Turner, KL and Arteaga, I and Hernández de Jesús, A and Ginn, B and Nian, Y and Dohan, D},
title = {Pragmatic sensemaking: Mapping the cultural work of people living with dementia and their care-partners.},
journal = {Social science & medicine (1982)},
volume = {409},
number = {},
pages = {119829},
doi = {10.1016/j.socscimed.2026.119829},
pmid = {42801851},
issn = {1873-5347},
abstract = {RATIONALE: Alzheimer's disease and related dementias (ADRD) affect over 100 million people living with dementia (PLWD) and care-partners worldwide, creating intersecting challenges of brain change, social identity, and everyday routines. By examining how physiological and social dimensions intertwine, we chart implications for social scientific models and medical framings of ADRD and complex biosocial conditions more broadly.

OBJECTIVE: We examine how people living with dementia (PLWD) and family care-partners make sense of, and respond to, life with dementia.

METHODS: We completed a team-based multi-site ethnography across three U.S. states: 314 site visits, 117 interviews, and four years of longitudinal observation. In addition to in-depth analysis of cases and accounts, we used network visualizations to map shared understandings (cultural schema) in respondent narratives.

RESULTS: Participants engaged in pragmatic sensemaking: adapting available meanings to make sense of shifting challenges, rather than holding to a singular narrative of life with dementia. Four schemas were empirically central in dementia narratives: health and medicine, social cognition, social roles, and change over time. Case analyses show how people combine and reconfigure these understandings as their circumstances shift. Participants understand ADRD not as solely 'loss' or 'journey,' medical challenge or social circumstance, but as a phenomenon involving all of these, and requiring adaptive responses.

CONCLUSIONS: Although life with dementia can vary with wealth, biography, disease type and stage, people across divergent circumstances relied on pragmatic sensemaking, adapting available meanings to address practical and existential challenges of life alongside ADRD. Pairing computational analysis with ethnography makes this interpretive work visible and reveals patterns conventional accounts overlook, with implications for scholarship on how people respond to complex conditions like ADRD that resist reduction to purely medical or social elements.},
}

@article {pmid42801993,
year = {2026},
author = {Wang, J and Tu, X and Yang, R and Kang, J and Gu, A and Han, B and Kai, G},
title = {Protocatechuic acid alleviates the progression of Alzheimer's disease by regulating p53/GADD45/MAPK signaling pathway.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110512},
doi = {10.1016/j.jnutbio.2026.110512},
pmid = {42801993},
issn = {1873-4847},
abstract = {Alzheimer's disease (AD) is a prevalent neurodegenerative disorder worldwide lacking effective treatments. Protocatechuic acid (PCA), a natural polyphenol found in various foods and medicinal herbs, exhibits diverse bioactivities; but its role in AD remains unclear. This study investigated the neuroprotective effects and mechanisms of PCA. In vitro, PCA significantly attenuated glutamic-induced cytotoxicity, oxidative stress, calcium influx, and apoptosis in PC12, SH-SY5Y, and HT22 cells. In vivo, PCA improved cognitive performance in the Morris water maze, open field, and novel object recognition tests in a D-galactose/AlCl3-induced AD mice, and mitigated hippocampal and cortical histopathological damage. Integrated transcriptomic and network pharmacology analyses identified the apoptosis, p53, and MAPK as key pathways. RT-qPCR and western blot analyses revealed that PCA downregulated p53, GADD45B, GADD45G, and phosphorylated p38. Collectively, these findings demonstrate that PCA alleviates AD progression by inhibiting the p53/GADD45/MAPK axis, positioning it as a promising natural candidate for AD prevention.},
}

@article {pmid42802672,
year = {2026},
author = {Paes, VR and Pereira, FL and Silva, CM and de Moraes, FOC and Padrão, IL and Justo, AFO and Rodriguez, RD and Naslavsky, MS and Leite, REP and Pasqualucci, CAG and Zatz, M and Ferriolli, E and Suemoto, CK and Grinberg, LT},
title = {Lewy Body Disease Across Aging: Clinical and Neuropathological Correlates in a Population Brain Bank.},
journal = {Movement disorders : official journal of the Movement Disorder Society},
volume = {},
number = {},
pages = {},
doi = {10.1002/mds.70515},
pmid = {42802672},
issn = {1531-8257},
support = {K24AG053435/NH/NIH HHS/United States ; R01AG075802/NH/NIH HHS/United States ; 2020/14339-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2024/03917-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; AARG-20-678884/ALZ/Alzheimer's Association/United States ; 24CBIDR-1185483/ALZ/Alzheimer's Association/United States ; AARGD-22-972378/ALZ/Alzheimer's Association/United States ; //Global Brain Health Institute/ ; },
abstract = {BACKGROUND: Lewy body disease (LBD) is defined by neuronal α-synuclein pathology, but how Braak-staged LBD relates to mixed neuropathology and clinical manifestations within a single population-based cohort remains incompletely characterized. This is especially relevant in cohorts enriched for younger individuals, which may better inform real-world biomarker interpretation and predictive value than cohorts dominated by the oldest-old.

OBJECTIVE: The objective of this study was to determine how Braak-staged LBD relates to age, mixed neuropathology, and clinical manifestations within a single population-based cohort.

METHODS: We studied 2480 autopsied participants from the Biobank for Aging Studies in São Paulo, Brazil (mean age 73.25 ± 14.15 years, 49.7% female, mean education 5.17 ± 4.23 years; 2004-2025). Structured postmortem informant interviews assessed cognition (CDR-SB), parkinsonian symptoms (Tanner questionnaire), neuropsychiatric symptoms (Neuropsychiatric Inventory), and family-reported premortem Parkinson's disease (PD) diagnosis. Brains were staged using Braak Parkinson's disease (Braak-PD) staging and evaluated for copathologies.

RESULTS: Overall, 10.4% had LBD, increasing from 0.7% among those younger than 50 years to 20.0% among those aged ≥90 years. Advanced Braak-PD was associated with greater Alzheimer's disease-related neuropathology, TDP-43 pathology, and cerebral amyloid angiopathy. Approximately 26.1% of individuals with Braak-PD V-VI had a family-reported premortem PD diagnosis. In adjusted models, Braak-PD V-VI remained associated with worse cognition (β 3.03, 95% confidence interval [CI]: 1.93-4.14), hallucinations (odds ratio [OR] 3.87, 95% CI: 2.27-6.61), and delusions (OR 2.79, 95% CI: 1.61-4.82), whereas total parkinsonism score was not independently associated. Nocturnal disturbances were already associated with Braak-PD I-II (OR 2.25, 95% CI: 1.13-4.47).

CONCLUSIONS: In this population-based cohort, LBD becomes more frequent with age, occurs in a mixed-pathology context, and is more strongly expressed through cognition and psychosis-related symptoms than through caregiver-reported parkinsonian burden. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.},
}

@article {pmid42802722,
year = {2026},
author = {Zhang, Y and Song, R and Wang, J and Chen, B and Sun, H and Ren, X and Ju, L and Feng, X and Wang, X and Qin, G},
title = {Traditional Chinese medicine for Alzheimer's disease: pathological mechanisms and multi-target interventions.},
journal = {3 Biotech},
volume = {16},
number = {10},
pages = {449},
pmid = {42802722},
issn = {2190-572X},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder driven by multiple interconnected pathological mechanisms. This narrative review systematically searched major biomedical databases for relevant literature published between 2015 and 2026, using predefined keywords combined with manual supplementary searches. Two independent reviewers performed a qualitative screening based on relevance, involving the iterative review of titles, abstracts, and full texts. A targeted selection of representative, high-quality studies centered on TCM and AD pathogenesis/mechanisms was then conducted. Ultimately, studies were included in the narrative review for the mechanistic synthesis of TCM against AD. This review summarizes seven core AD mechanisms, including the Aβ cascade, Tau abnormalities, Neuroinflammation, Regulated cell death, Synaptic plasticity impairment, Gut microbiota-brain axis imbalance, and Oxidative stress, and critically discusses the multi‑target interventions of TCM via key molecules such as GSK-3β, BACE1, SIRT1, NF‑κB, NLRP3, PINK1/Parkin, AMPK, BDNF, PSD‑95, and the Nrf2/HO‑1 pathway. GSK‑3β and NF‑κB act as central hubs linking Aβ/Tau pathology to neuroinflammation, while AMPK, SIRT1, and Nrf2/HO‑1 regulate metabolic and redox homeostasis, PINK1/Parkin control mitophagy, and BDNF/PSD‑95 determine synaptic integrity. TCM's therapeutic superiority lies in its simultaneous modulation of this entire hierarchical network, representing a multi‑target strategy that conventional single‑target drugs cannot replicate. By concurrently modulating these distinct yet interacting nodes, TCM establishes a synergistic therapeutic network that reduces Aβ deposition, attenuates Tau hyperphosphorylation, and mitigates neuronal damage, offering a novel direction for future AD research.},
}

@article {pmid42802826,
year = {2026},
author = {Lee, SY and Mizuguchi, T and Kim, HJ and Kim, YE and Hanna, C and Kim, WJ and Lee, GH and Kim, A and Park, JY and Chung, EJ and Jang, H and Jung, NY and Lee, SM and Seo, SW and Koh, SH and Zetterberg, H and G Apostolova, L and Matsumoto, N and Moon, SY and Kim, EJ and , },
title = {Screening GGC repeat expansion in the NOTCH2NLC in early-onset dementia: The Longitudinal Study of Early Onset Dementia and Family Members (LEAF) Study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70482},
pmid = {42802826},
issn = {2352-8729},
abstract = {BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is neurodegenerative disorder caused by GGC repeat expansion in NOTCH2NLC. Given its frequency in young East Asian adults and overlap with cognitive impairment in young adults, a key feature of early-onset dementia (EOD), we screened NOTCH2NLC GGC repeat expansions in Korean patients with EOD.

METHODS: We screened NOTCH2NLC GGC repeat expansions in 410 Korean patients with EOD using repeat-primed and amplicon length polymerase chain reaction. Plasma biomarkers in adult-onset leukodystrophy were additionally measured using Simoa-based ultrasensitive immunoassays.

RESULTS: GGC repeat expansions were not identified in early-onset Alzheimer's disease (AD) or frontotemporal dementia (FTD), while four of eleven patients with adult-onset leukodystrophy (36.3%) had abnormal expansions. Plasma neurofilament light chain (NfL) level was lower in NIID than in colony-stimulating factor 1 receptor-related disorder.

DISCUSSION: These findings support recent arguments that the concept of NOTCH2NLC-related GGC repeat expansion disorder (NRED) should be reconsidered. Plasma NfL may be useful in differential diagnosis of adult-onset leukodystrophy.},
}

@article {pmid42802831,
year = {2026},
author = {Miklitz, C and Shrestha, M and Philipp, W and Henk, N and Sprinkart, AM and Block, W and Luetkens, JA and Radbruch, A and Lehnen, NC and Nowak, S},
title = {Locally deployed large language model for real-world lecanemab eligibility pre-screening.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {3},
pages = {e70495},
pmid = {42802831},
issn = {2352-8729},
abstract = {INTRODUCTION: The introduction of disease-modifying Alzheimer's therapies requires complex, labor-intensive patient screening. Cloud-based large language models (LLMs) could support this task but are often unsuitable for routine care due to data protection constraints.

METHODS: We evaluated an on-premises, open-weights LLM (gpt-oss-120b) for automated extraction of therapy-relevant variables for lecanemab eligibility from German memory clinic reports. In a two-stage design, LLM-based extraction prompts, a deterministic rule-based extractor, and a shared downstream rule-based classifier were optimized on a development set (n = 97) and evaluated on an independent hold-out set (n = 99), with expert consensus as ground truth.

RESULTS: The LLM-based pipeline achieved 94% accuracy and a Cohen's kappa of 0.90 on the hold-out set, significantly surpassing the rule-based comparator (80% accuracy) and demonstrating performance comparable to human experts.

DISCUSSION: A locally deployed, on-premises LLM may assist eligibility screening as a triage support tool, potentially facilitating access to novel therapies without compromising patient data privacy.},
}

@article {pmid42802939,
year = {2026},
author = {Koch, G and Martorana, A and Santarnecchi, E},
title = {From network observation to network intervention in Alzheimer's disease.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag329},
pmid = {42802939},
issn = {1460-2156},
}

@article {pmid42803225,
year = {2026},
author = {Jamhour, RMAQ and Salman, HA and Alshammari, M and Almuqati, AF and Fayed, MH and Al-Mazaideh, GM},
title = {Alzheimer's Disease: Silent Erosion of Memory - From Discovery to Modern Crisis and the Quest for a Cure.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050423446251215051844},
pmid = {42803225},
issn = {1875-5828},
abstract = {Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive abilities and memory impairment, representing the most common form of dementia worldwide. First described by Alois Alzheimer in 1906, AD continues to pose significant global health and socioeconomic challenges, with incidence anticipated to exceed 14 million cases by 2060. Despite decades of investigation, the specific pathophysiology -comprising multifactorial mechanisms such as genetic predisposition, environmental influences, lifestyle factors, amyloid-β (Aβ) plaques, neurofibrillary tangles, tau pathology, as well as vascular disease - remains incompletely understood. This review provides a comprehensive summary of the current knowledge regarding these mechanisms, and it explores the field's new therapeutic modalities, such as monoclonal antibodies, ultrasound-based treatments, and novel diagnostic tools based on biomarkers. It also discusses the socioeconomic burden of AD and regional challenges in the Middle East, as well as the impact of the COVID-19 pandemic on dementia care. While many of AD's underlying causes are aggressive and difficult to treat, new research in genetics, natural compounds, and groundbreaking therapies offers hope for better diagnosis and treatment. Above all, this study emphasizes the importance of having more effective chemotherapeutic or radiological approaches for ADs, as well as a robust medical system capable of providing these treatments to the patients.},
}

@article {pmid42803376,
year = {2026},
author = {Cutty, M and Maldonado, L and Johnson, J and Pfeil, C and Simpson, KN and Knox, S},
title = {Clinical Group Assignment in Home Health Care for Medicare Beneficiaries With ADRD: A 2019 Pre-PDGM Simulation.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261489746},
doi = {10.1177/07334648261489746},
pmid = {42803376},
issn = {1552-4523},
abstract = {BackgroundThe Patient-Driven Groupings Model (PDGM) assigns home health episodes to clinical groups using primary diagnosis codes. The implications of this approach for beneficiaries with ADRD, whose condition is rarely coded as primary, are unclear.ObjectiveTo compare simulated PDGM clinical group assignment between ADRD-highly likely and ADRD-unlikely episodes.MethodsUsing national 2019 Medicare fee-for-service data, we simulated clinical group assignment and compared primary diagnosis profiles before and after 1:1 propensity score matching.ResultsNine in ten ADRD-highly likely episodes carried a non-ADRD primary diagnosis. After matching on demographics, comorbidity, and functional and cognitive status, clinical group assignment differences between cohorts attenuated but persisted. Most strikingly, ADRD-highly likely episodes were nearly 12 times as frequently assigned to Behavioral Health, the group with the lowest average payment weight, and comprised 92.1% of all matched Behavioral Health episodes. Within clinical groups, primary diagnosis profiles differed between cohorts, suggesting distinct care needs.},
}

@article {pmid42803705,
year = {2026},
author = {Kandilakis, CL and Skondra, M and Papageorgiou, G and Konidari, E and Papalexiou, V and Papadopoulos, L and Charalampopoulou, M and Georgiou, EZ and Marouli, I and Malagkoniari, LM and Kostakiotis, A and Economou, P and Felemegkas, P and Alexopoulos, P},
title = {Comparison of Clock Drawing Test and Rey Complex Figure Test scoring methods for detecting mild and major neurocognitive disorder due to Alzheimer's disease in a real-world clinical setting.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261490548},
doi = {10.1177/13872877261490548},
pmid = {42803705},
issn = {1875-8908},
abstract = {BackgroundDirect comparisons of different scoring methods of the Clock Drawing Test (CDT) and the copy trial of the Rey Complex Figure Test (RCFT) remain limited.ObjectiveThe study aimed to compare the effectiveness of four- and two scoring systems of the CDT and the RCFT, respectively, in detecting mild neurocognitive disorder (MildND) due to Alzheimer's disease (AD) and major neurocognitive disorder (MajorND) due to AD.MethodsThe study included 141 cognitively unimpaired individuals, 209 people with MildND and 76 with MajorND due to AD. The 3-point CDT scoring method (CDT3), the Gestalt-, Freund-, and Rouleau methods were employed, while the RCFT Copy trial was scored with the 36-point Taylor system and the RCFT central-items (RCFTci) method. Statistical analyses included comparison analyses and proportional odds logistic regression (POLR) models, while stratified bootstrap resampling was used to repeatedly partition the sample into training and validation sets (70/30 ratio).ResultsThe Rouleau CDT scoring method achieved the highest classification performance (F1 = 0.67; 95% CI: 0.59-0.74), followed by the Gestalt method (F1 = 0.65; 95% CI: 0.57-0.72), the Freund method (F1 = 0.64; 95% CI: 0.56-0.72), and the CDT3 (F1 = 0.63; 95% CI: 0.55-0.71). The CDT Rouleau method and the RCFT Copy trial showed similar performance (F1 = 0.67; 95% CI: 0.59-0.74), while RCFTci was less effective (F1 = 0.62; 95% CI: 0.54-0.70).ConclusionsThe CDT and RCFT Copy trial demonstrated comparable diagnostic accuracy, yet their distinct characteristics (administration time, scoring complexity) may guide test selection across healthcare settings.},
}

@article {pmid42803706,
year = {2026},
author = {Zhang, J and Jia, X and Zhang, Y and Wang, Q and Liu, P and Jia, X and Yang, Q},
title = {Synergistic effects of cerebrovascular reactivity and gray matter volume on executive function in aging.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261487149},
doi = {10.1177/13872877261487149},
pmid = {42803706},
issn = {1875-8908},
abstract = {BackgroundAge-related impairments in cerebrovascular reactivity (CVR) and gray matter volume (GMV) both contribute to cognitive decline, yet their regional interplay and joint impact on cognition remain unclear.ObjectiveTo investigate how CVR and GMV are coupled and interact regionally to influence cognition in normal aging.MethodsWe examined 181 healthy younger adults (18-34 years) and 120 older adults (60-89 years). CVR and GMV (% intracranial volume) in major brain lobes were quantified using resting-state multi-echo functional MRI and structural MRI, respectively. Age-related alterations were defined by standardizing older adults' values relative to the younger group. Spearman correlations, linear regression models, and interaction analyses were performed.ResultsCVR and GMV were not significantly correlated across frontal, temporal, parietal, or occipital lobes (ρ: -0.15 to -0.06; all p > 0.05). However, significant CVR × GMV interaction effects on executive function were found in parietal and occipital lobes (p-interaction=0.015 and 0.026). In the occipital lobe, compared with the "low CVR decline + low GMV loss" group, "high CVR decline + low GMV loss" (β=-0.47, p = 0.004) and "high CVR decline + high GMV loss" (β=-0.60, p < 0.001), but not "low CVR decline + high GMV loss" (β=-0.23, p = 0.127), were significantly associated with poorer executive function.ConclusionsCVR and GMV interacted to support executive function in parietal and occipital lobes. Occipital CVR decline linked to poorer executive performance irrespective of GMV status. These findings highlight the importance of multi-modal, cross-scale assessments and suggest CVR as a sensitive marker of executive decline beyond structural measures alone.},
}

@article {pmid42803707,
year = {2026},
author = {Motolese, F and Ursini, F and Norata, D and Capone, F and Sapio, E and Di Giesi, ML and Selvaggi, SA and Annesi, G and Rossi, M and Calandrelli, R and Mallio, CA and Bernetti, C and Tondo, M and Zobel, BB and Faiella, E and Pilato, F and Di Lazzaro, V},
title = {Estimating anti-amyloid therapy eligibility in Alzheimer's disease: A real-world retrospective study from an Italian memory clinic.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261488813},
doi = {10.1177/13872877261488813},
pmid = {42803707},
issn = {1875-8908},
abstract = {BackgroundAmyloid-targeting therapies (ATTs) such as donanemab may change the management of Alzheimer's disease (AD). However, ATTs require meticulous eligibility assessment to optimize the benefit-to-risk ratio.ObjectiveTo quantify the proportion of patients eligible for donanemab in a real-world Italian memory clinic, and to assess how this proportion changes under stricter biological criteria.MethodsIn this real-world study, we retrospectively evaluated consecutive patients with new-onset cognitive symptoms at the Fondazione Policlinico Campus Bio-Medico between October 2024 and March 2026. Amyloid status was determined by cerebrospinal fluid (CSF) examination or PET-imaging. Eligibility was determined using European Medicines Agency and Appropriate Use Recommendations (AUR).ResultsWe included 179 consecutive patients (mean age 72.3 ± 7.2 years, 77 [44.0%] female) with mean Mini-Mental State Examination score 26.4 ± 3.3. A clinical diagnosis of AD was made in 78 (43.6%), and 46 (25.7%) were amyloid-positive. Overall, 21 patients (11.7% of the total cohort and 45.6% of amyloid-positive individuals) fulfilled all AUR criteria for donanemab. Requiring concomitant CSF p-tau positivity further reduced eligibility to 13 patients, accounting for 7.3% of the total cohort.ConclusionsAlthough ATTs represent a novel therapeutic option that targets the underlying AD pathology, their real-world applicability remains limited to a small patient fraction, narrowing further under strict biological stratification. Concerns regarding cost-effectiveness and practical implementation persist. Early-stage AD diagnosis and precise stratification are paramount to ensure that the promise of disease-modifying therapies can be translated into tangible clinical impact.},
}

@article {pmid42803709,
year = {2026},
author = {Wen, S and Liu, J and Wang, J and Mao, L and Zhang, Q and Wang, X and Ding, J},
title = {Subregion-specific temporal lobe EEG signatures in amnestic mild cognitive impairment: Evidence from high-density EEG.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261487173},
doi = {10.1177/13872877261487173},
pmid = {42803709},
issn = {1875-8908},
abstract = {BackgroundAmnestic mild cognitive impairment (aMCI), a prodromal stage associated with an increased risk of Alzheimer's disease (AD), is characterized by early neural network dysfunction. The temporal lobe is among the earliest affected regions, yet conventional electroencephalography (EEG) provides limited information regarding subregional electrophysiological alterations.ObjectiveTo characterize temporal-subregional electrophysiological features in aMCI using high-density EEG (HD-EEG).MethodsFifty-five individuals with aMCI and 35 cognitively normal controls underwent neuropsychological assessment and resting-state 128-channel HD-EEG recording. Spectral power was quantified across the whole temporal lobe and its anterior, middle, and posterior subregions. Group differences were assessed using Welch's t-tests and Mann-Whitney U tests. Associations between EEG measures and cognitive performance were examined using Spearman correlation analyses. Exploratory receiver operating characteristic (ROC) and multivariable classification analyses were performed to evaluate discriminatory performance.ResultsCompared with controls, individuals with aMCI showed significantly poorer cognitive performance. HD-EEG analyses revealed increased gamma-band activity across bilateral temporal subregions, whereas elevated delta power and theta/beta ratios were primarily localized to right temporal subregions. Right temporal delta activity was negatively associated with memory performance. Connectivity analyses demonstrated enhanced fast-frequency coupling involving temporal regions, with particularly evident alterations in the left posterior temporal subregion. Classification analyses showed that gamma-band measures derived from left temporal subregions achieved discriminatory performance comparable to conventional whole-temporal measures.ConclusionsHD-EEG identified subregion-specific temporal-lobe electrophysiological alterations in aMCI. Temporal-subregional EEG profiling may provide additional electrophysiological information beyond conventional whole-lobe analyses and improve the characterization of aMCI-related neural alterations.},
}

@article {pmid42803710,
year = {2026},
author = {Campedelli, L and Cicoli, A and Lastretti, M and Spagna, S and D'Aleo, E and Costa, A},
title = {Lithium exposure and risk of dementia and Alzheimer's disease: A systematic review and meta-analysis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261488808},
doi = {10.1177/13872877261488808},
pmid = {42803710},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is the most common cause of dementia, affecting over 55 million people worldwide with no established disease-modifying treatments. Lithium has emerged as a potential neuroprotective agent through multiple molecular mechanisms, and observational studies suggest reduced dementia risk among users, but evidence synthesis is needed.ObjectiveTo evaluate the association between lithium exposure and dementia incidence through systematic review and meta-analysis.MethodsWe conducted a systematic review following PRISMA 2020 guidelines, searching major databases through December 2024. Random-effects meta-analyses with Hartung-Knapp-Sidik-Jonkman adjustment were performed.ResultsTwenty-three primary studies with original data (n > 1.2 million) were included in qualitative synthesis; 11 provided extractable quantitative data, including 8 individual-level and 3 ecological studies. Four cohort studies showed a pooled hazard ratio (HR) of 0.633 (95% CI: 0.517-0.775; p = 0.003), indicating ∼37% lower dementia risk with lithium. Two individual-level studies showed HR 0.656 (95% CI: 0.427-1.009; p = 0.052) for AD diagnosis. Three randomized controlled trials (RCTs) of cognitive outcomes yielded SMD -0.410 (95% CI: -0.810 to -0.020; p = 0.040) based on 229 participants. Two ecological studies using incidence rate ratios (IRR 0.830, 95% CI: 0.810-0.850) were directionally consistent. Substantial heterogeneity reflected clinical diversity, with consistent protective effects across subgroups.ConclusionsLithium exposure was consistently associated with reduced dementia risk. While observational evidence precludes definitive causal inferences, the magnitude, consistency, and biological plausibility support lithium as a promising candidate for dementia prevention research. Large-scale, long-term RCTs are needed to establish causality.},
}

@article {pmid42803712,
year = {2026},
author = {Xiong, SY and Zhao, YL and Fu, Y and Li, QY and Zhang, DD and Qiu, SD and Wang, YC and Yan, Z and Zhang, W and Tan, L},
title = {Associations of social isolation and its subdomains with cognition and cerebrospinal fluid amyloid pathologies in non-demented adults: The CABLE study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489152},
doi = {10.1177/13872877261489152},
pmid = {42803712},
issn = {1875-8908},
abstract = {BackgroundSocial isolation is increasingly recognized as a modifiable risk factor for cognitive impairment. However, the associations with Alzheimer's disease (AD)-related cerebrospinal fluid (CSF) biomarkers remain unexplored.ObjectiveTo evaluate the relationships between social isolation, cognition, and CSF biomarkers and how these are influenced by other factors.MethodsIn this cross-sectional study, 957 non-demented adults from the Chinese Alzheimer's Biomarker and LifestyLE (CABLE) study (mean age: 64.19 years; 46% male) were included. Multiple linear regression models were used to analyze the associations of social isolation and its subdomains (social networks, marital status, and social activities) with cognition and CSF biomarkers after adjustment for age, gender, education, and APOE ɛ4 allele status. Interactive, stratified, and sensitivity analyses were further conducted.ResultsSocial isolation was significantly associated with worse cognitive performance, including lower MMSE (β=-0.09, PFDR=0.008) and MoCA scores (β=-0.11, PFDR=0.002). Social isolation was also associated with CSF amyloid pathology, including decreased Aβ42 (β=-0.14, PFDR=0.004), decreased Aβ40 (β=-0.16, PFDR<0.001), and increased T-tau/Aβ42 ratio (β=0.12, PFDR=0.016) levels. Specifically, smaller social networks were correlated with poorer cognition and decreased CSF Aβ42 and Aβ40 levels, while being without a spouse was associated with decreased CSF Aβ42 and Aβ40 levels and increased P-tau/Aβ42 and T-tau/Aβ42 ratios. Associations were primarily observed among males and APOE ε4 non-carriers in subgroup analyses. Sensitivity analyses confirmed the robustness of our findings.ConclusionsSocial isolation, particularly smaller social networks and being without a spouse, is associated with worse cognitive performance and early CSF amyloid-related biomarkers levels in non-demented adults.},
}

@article {pmid42803713,
year = {2026},
author = {Ippati, S and Torelli, F and Zamboni, G and Iavarone, A and Martorana, A and Botello, B and Cotton, S and Walker, C and Phillips, Z and Avitabile, A},
title = {Diagnosis and management of mild cognitive impairment and mild Alzheimer's disease dementia: Findings from an Italian real-world survey.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261490595},
doi = {10.1177/13872877261490595},
pmid = {42803713},
issn = {1875-8908},
abstract = {BackgroundThe identification and early diagnosis of mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) dementia are critical for timely intervention, yet implementation of biomarker-based diagnostics in the Italian healthcare system remains limited.ObjectiveTo characterize the real-world diagnostic journey, barriers, and management pathways of MCI and mild AD dementia patients in Italy.MethodsData were drawn from the Adelphi Real World Dementia Disease Specific Programme™, a cross-sectional survey of Italian primary care physicians and specialists. Physicians reported on diagnostic assessments, biomarker testing, and treatment initiation for consulting patients with MCI/mild AD dementia.ResultsPhysicians provided data on 325 patients (mean age: 74.1 years; 48.3% female). Patients aged ≥75 had lower Mini-Mental State Examination scores at survey (p = 0.0028) and diagnosis (p = 0.0223) than patients aged <75 years. Short-term memory loss (87.6%) was the most common symptom. Delays in diagnosis were most commonly attributed to limited specialist access (55.8%), prolonged interval between consultations (27.0%), and restricted diagnostic resources (20.4%). Magnetic resonance imaging was the primary imaging modality (65.7%), while biomarker testing such as cerebrospinal fluid and amyloid positron emission tomography were performed in 15.9% and 16.3% of cases, likely hindered by patient's reluctance and cost, respectively, as indicated by specialist-perceived challenges in using biomarkers for early symptomatic AD diagnosis. Patients whose treatment was initiated by specialists were commonly prescribed acetylcholinesterase inhibitors (72.8%).ConclusionsDelays in MCI and mild AD dementia diagnosis persist alongside systemic barriers and limited biomarker use. Improving referral pathways and biomarker access is essential for timely diagnosis and management.},
}

@article {pmid42803714,
year = {2026},
author = {Lôbo, RR and Santos, LTR and Peixoto Junior, AA and Macedo, DS},
title = {Alzheimer's disease polygenic risk scores and postoperative delirium: A promising marker, but not yet a clinical tool.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261491985},
doi = {10.1177/13872877261491985},
pmid = {42803714},
issn = {1875-8908},
abstract = {Recent advances in Alzheimer's disease (AD) biomarkers and genomics have raised interest in personalized approaches to related conditions such as postoperative delirium (POD). Chen et al. report a moderate association between AD polygenic risk scores (AD-PRS) and POD, suggesting genetic susceptibility as a marker of biological vulnerability. However, the clinical utility of AD-PRS remains uncertain, as the study does not demonstrate incremental predictive value over established clinical risk factors. At present, AD-PRS should be considered a research tool. Future studies should assess its predictive performance, cost-effectiveness, and ethical implementation in diverse populations.},
}

@article {pmid42803715,
year = {2026},
author = {Tang, L and Qiu, C and Chi, C and Liu, F and Zhu, X},
title = {Edentulism and cognitive transitions: A multi-state analysis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261487358},
doi = {10.1177/13872877261487358},
pmid = {42803715},
issn = {1875-8908},
abstract = {BackgroundEdentulism has been linked to cognitive decline, yet its effects on the transitions from normal cognition to dementia and ultimately death remain unclear.ObjectiveThis study aimed to evaluate how edentulism influences cognitive state transitions across the aging continuum.MethodsWe conducted a prospective cohort analysis of 22,205 adults aged 50 years or older from China, the USA, and England, with cognitive states assessed over a median follow-up of 12.3 years. Multi-state Markov models were used to estimate transition-specific hazard ratios (HR) and population attributable fractions (PAFs) for edentulism after adjusting for sociodemographic, behavioral, and health covariates. A Cox regression model was used to estimate edentulism associated with the risk of cognitive status and death.ResultsAt baseline, 7.41% of Chinese, 21.64% of US, and 14.24% of English participants were edentulous. During follow-up, 60.1% developed mild cognitive impairment (MCI), 13.6% of those progressed to dementia, and 36.0% died after dementia. Edentulism significantly increased the risk of transition from baseline to death (HR = 1.27, 95% CI:1.13, 1.42) and from MCI to dementia (HR = 1.26, 95% CI:1.12, 1.40). The corresponding PAFs were 4.58% and 6.52%, respectively. Subgroup analyses by age and sex yielded consistent results.ConclusionsEdentulism was associated with faster progression from MCI to dementia and higher death risk. These findings highlight the importance of oral health maintenance as a potential target for Alzheimer's disease and dementia prevention.},
}

@article {pmid42803718,
year = {2026},
author = {Lande, IS and Rozenberg, A and Stessman, J and Jacobs, JM},
title = {Age-dependent associations between physical activity and cognitive function in adults aged 70-100: A cross-sectional and longitudinal study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261487392},
doi = {10.1177/13872877261487392},
pmid = {42803718},
issn = {1875-8908},
abstract = {BackgroundWhile the protective effects of physical activity (PA) on cognitive function and risk for cognitive decline are well documented, it remains unclear if the preventive effect continues at advancing age.ObjectiveThis study aims to examine the association between PA and cognitive impairment between ages 70-100MethodsThe Jerusalem Cross-sectional and Longitudinal Study (1990-2023) prospectively follows a representative community-dwelling cohort born 1920-1921, combining follow-up of the original cohort with repeated recruitment of same-birth cohort participants at each age. During the study, assessments were performed at ages 70, 78, 85, 90, 95, and 100 (n = 604, 1024, 1222, 729, 508, 205, respectively). Comprehensive assessment included Mini-Mental State Examination (MMSE) defining cognitive impairment (≤23/30), and self-reported PA, dichotomized to Sedentary (PA-S) (<4 h weekly) versus Active (PA-A) (at least >4 h a week).ResultsAt ages 70, 78, 85, 90, 95, and 100 the frequency of PA-A was 53.5%, 77.0%, and declined to 64.3%, 16.0%, 25.5%, and 27.1%, respectively. In a longitudinal analysis, PA-S at baseline was found to have a statistically significant association with cognitive impairment at a later age between ages 78-85, 85-90: OR 2.61 (95%CI 1.38-4.82); OR 2.90 (95%CI 1.63- 5.11), respectively. At ages 90-95 a similar not statistically significant effect was found.ConclusionsPA is associated with better cognitive aging and lower risk for cognitive impairment in advanced age. Inclusion of very old adults extends evidence into an age rarely examined and demonstrates that promotion of PA remains relevant even at advanced ages.},
}

@article {pmid42803721,
year = {2026},
author = {Toledo, LG and Tourelle, M and Galvin, JE and Besser, LM},
title = {Associations between systemic inflammation, neighborhood tree canopy, and white matter hyperintensities: The healthy brain initiative.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261485596},
doi = {10.1177/13872877261485596},
pmid = {42803721},
issn = {1875-8908},
abstract = {BackgroundSystemic inflammation is associated with greater white matter hyperintensities (WMH), increasing risk of Alzheimer's disease. Neighborhood greenspaces (e.g., parks) have been associated with reduced inflammation and dementia risk and fewer WMH.ObjectiveTo examine whether systemic inflammation and neighborhood % tree canopy are independently associated with and interact to influence WMH.MethodsWe used cross-sectional data on 161 participants with magnetic resonance imaging (MRI) in University of Miami's Healthy Brain Initiative who were ≥ 50-years old with no to mild cognitive impairment. U.S. Forest Service tree canopy data (2021) were used to derive tree canopy percentage per Census tract. High-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, was categorized as low/moderate (0-3 mg/L) and high (>3 mg/L). Total WMH volume was derived from structural MRI. Multivariable linear regression examined independent associations of hs-CRP and WMH and % tree canopy and WMH, and the association between a four-category hs-CRP-tree canopy variable (based on median cut points) and WMH.ResultsParticipants were 68.7 ± 9.3 years old and 70% were female. Higher hs-CRP was associated with greater WMH, and greater neighborhood % tree canopy was associated with fewer WMH. Compared to those with higher hs-CRP and lower % tree canopy, those with higher hs-CRP and greater % tree canopy had fewer WMH.ConclusionsHigher systemic inflammation and greater neighborhood % tree canopy were independently associated with WMH, and our findings suggest that they interact to influence WMH (e.g., in those with higher inflammation, having greater neighborhood tree canopy associated with lower WMH).},
}

@article {pmid42803723,
year = {2026},
author = {Yeo, D and Kim, S and Lee, K and Son, Y and Lee, H and Kim, S and Hwang, HS and Yon, DK},
title = {Spirometry-defined obstructive airflow limitation and risk of incident dementia: A nationwide cohort study in South Korea.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489594},
doi = {10.1177/13872877261489594},
pmid = {42803723},
issn = {1875-8908},
abstract = {BackgroundWhether spirometry-defined airflow limitation is independently associated with incident dementia and related disability burden remains unclear.ObjectiveTo investigate the association between obstructive airflow limitation and incident dementia and to estimate dementia-related years lived with disability (YLDs) in a nationwide cohort.MethodsWe conducted a nationwide population-based cohort study linking the Korea National Health and Nutrition Examination Survey (2014-2021) with national health insurance claims data. Adults aged ≥40 years with baseline spirometry and no prior dementia were included. Airflow limitation was defined as FEV1/FVC <0.70, with severity classified by percent-predicted FEV1. Inverse probability of treatment weighting balanced baseline covariates. Cox models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident dementia. Dementia-related YLDs were calculated using Global Burden of Disease Study weights.ResultsDuring follow-up (2014-2023), 760 cases (4.79%) of dementia occurred among 15,854 adults. Normal pulmonary function was associated with lower dementia risk than airflow limitation (aHR, 0.62 [95% CI, 0.50-0.77]). Within the normal range, risk decreased across increasing FEV1/FVC tertiles (T1 [lowest], 0.76 [0.60-0.96]; T2, 0.63 [0.49-0.81]; T3 [highest], 0.45 [0.34-0.59]). Among those with airflow limitation, risk increased with severity (mild: 1.32 [0.95-1.84]; moderate: 1.87 [1.41-2.46]). Greater severity was also associated with higher YLDs.ConclusionsSpirometry-defined airflow limitation was associated with higher dementia risk and greater disability burden, suggesting impaired pulmonary function as a potential factor in dementia risk stratification and brain health.},
}

@article {pmid42803724,
year = {2026},
author = {Bruun, M and Rune Nielsen, T and Waldemar, G and Frederiksen, KS},
title = {Older adults' attitudes toward knowing their risk of Alzheimer's disease and preclinical diagnostic communication: A nationwide study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261489585},
doi = {10.1177/13872877261489585},
pmid = {42803724},
issn = {1875-8908},
abstract = {BackgroundCommunication about biomarkers and disclosure of Alzheimer's disease pathology is challenging. Earlier diagnosis has intensified this challenge, but evidence regarding communication of positive biomarker results for Alzheimer's disease to individuals with subjective cognitive decline remains limited.ObjectiveThe study aimed to investigate older adults' attitude toward knowing their risk of Alzheimer's disease, preferences regarding pre-biomarker counseling and diagnostic disclosure, and their views on the use of artificial intelligence in the diagnostic process when presented with a hypothetical scenario of subjective cognitive decline.MethodsWe conducted a cross-sectional nationwide questionnaire survey among an age-selected, sex- and residence-balanced sample from the Danish Civil Registration System where individuals with dementia, nursing home residency, or dementia medication use were excluded. An online questionnaire was sent to 30,000 participants.ResultsA total of 12,939 participants (aged 55-84 years, 53.3% female) answered at least one questionnaire item (response rate: 43.1%). More than two-thirds of the participants were interested in knowing their Alzheimer's disease risk status (76.4%). Information on treatment options, test reliability and risk prediction, along with written material, personal interaction and follow-up consultation, were rated as the most important topics. Simple graphical figures were preferred to accompany risk communication. Finally, 56.4% were positive toward use of artificial intelligence in diagnostics by physicians.ConclusionsOlder adults are interested in knowing their risk of developing Alzheimer's disease and trust physicians' use of artificial intelligence in the diagnostic process. Moreover, their preferences regarding information and methodology may help improve the current guidelines.},
}

@article {pmid42803726,
year = {2026},
author = {Wang, X and Huang, Y and Li, J},
title = {Integrating transcriptomic data to identify calmodulin-related diagnostic biomarkers for Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261487604},
doi = {10.1177/13872877261487604},
pmid = {42803726},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is driven by amyloid-β, tau protein, and neuroinflammation. Calmodulin-mediated calcium signaling centrally links synaptic dysfunction, tauopathy, and inflammation, making it a key mechanistic and therapeutic target.ObjectiveTo identify calmodulin-related diagnostic biomarkers for AD and explore associated immune profiles and molecular subtypes.MethodsThe present work utilized integrative bioinformatics for the characterization of calmodulin-related genes in AD. Differentially expressed calmodulin-related genes were identified from Gene Expression Omnibus datasets and the Human Protein Atlas. Core genes were screened using weighted gene co-expression network analysis combined with three machine learning algorithms (Least Absolute Shrinkage and Selection Operator, random forest, and Support Vector Machine), from which a diagnostic model was subsequently constructed and validated. Immune infiltration was evaluated via ssGSEA and CIBERSORT, transcription factor and ceRNA regulatory networks were established, and small-molecule drugs were predicted. Consensus clustering was further applied to define molecular subtypes.ResultsFrom 50 differentially expressed genes, three core genes-MKNK2, ITPKB, and CEP97-showed strong diagnostic performance. Immune cell alterations were uncovered, regulatory networks and drug candidates predicted, and consensus clustering divided AD patients into two distinct subtypes.ConclusionsITPKB, MKNK2, and CEP97 are identified as calmodulin-related AD biomarkers linked to immune infiltration and subtyping, with potential for early diagnosis and novel therapies.},
}

@article {pmid42803728,
year = {2026},
author = {Ali, M and Shabbir, H and Shaharyar, M and Mukesh, S and Rodriguez, A and Afshani, M and Kalra, D and Koriesh, A},
title = {Efficacy and safety of aducanumab, lecanemab, and donanemab in Alzheimer's disease: A meta-analysis of randomized controlled trials.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261488812},
doi = {10.1177/13872877261488812},
pmid = {42803728},
issn = {1875-8908},
abstract = {BackgroundAnti-amyloid monoclonal antibodies offer a treatment strategy for early Alzheimer's disease, but their modest efficacy must be weighed against important safety concerns.ObjectiveTo evaluate the efficacy and safety of aducanumab, lecanemab, and donanemab in randomized placebo-controlled trials.MethodsPubMed, Cochrane, and ClinicalTrials.gov were searched through February 2026 for randomized placebo-controlled trials evaluating aducanumab, lecanemab, or donanemab in early symptomatic Alzheimer's disease. Outcomes included Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Mini-Mental State Examination (MMSE), amyloid-related imaging abnormalities-edema/effusion (ARIA-E), amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H), and APOE ε4-stratified ARIA-E. Random-effects meta-analyses were performed.ResultsSeven trials were included. Treatment favored intervention for ADAS-Cog (SMD -0.15, 95% CI -0.21 to -0.10), CDR-SB (MD -0.41, 95% CI -0.63 to -0.18), and MMSE (MD 0.44, 95% CI 0.03 to 0.86), although effects were small. Treatment increased ARIA-E (23.9% versus 1.9%; RR 11.65, 95% CI 9.06 to 14.99) and ARIA-H (16.8% versus 6.8%; RR 2.45, 95% CI 1.94 to 3.09). Among treated participants with APOE ε4-stratified ARIA-E data, APOE ε4 carriers had higher ARIA-E risk than non-carriers (29.3% versus 13.8%; RR 2.10, 95% CI 1.67 to 2.64). Brain-volume loss, ventricular enlargement, and treatment-related deaths were narratively identified but not pooled.ConclusionsAducanumab, lecanemab, and donanemab showed statistically significant but small slowing of decline that may not reach patient-perceptible clinical meaningfulness. Increased ARIA risk and additional safety signals support cautious selection, imaging surveillance, and individualized risk-benefit discussions.},
}

@article {pmid42798752,
year = {2026},
author = {Sipilä, J and Heervä, E and Mehdiyeva, A and Kaasinen, V},
title = {Epidemiological associations between neurodegeneration and cancer - time to refine our research approach.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/17582024.2026.2740131},
pmid = {42798752},
issn = {1758-2032},
abstract = {Cancer and neurodegenerative diseases are devastating aging-related disorders. Epidemiological data suggest a general inverse risk association between them, the mechanisms of which might provide new avenues for developing treatments and prevention strategies. In addition to this observation, meta-analyses have provided some conflicting results, apparently related to disease characterization, data validity, survival bias and unhandled exposure to risk factors. Taking these into account it seems that the association might be specific to certain types of cancers and particular types of neurodegenerative diseases. It should also be noted that, in some cases, the association is positive. Future studies investigating epidemiological association between cancer and neurodegeneration need to take into account several methodological aspects to provide data that can inform basic and translational studies on pathomechanisms. Most importantly, diagnoses must be accurate and validated, disease subtypes should be precisely defined and stratified, sources of possible bias must be explicitly addressed, time-varying trends should be analyzed as potential confounders and null association must always be published.},
}

@article {pmid42798843,
year = {2026},
author = {Gerasimov, E and Fedorov, E and Bezprozvanny, I and Pchitskaya, E},
title = {Dissecting neuronal circuit function and dysfunction in Alzheimer's disease mouse models: from conventional calcium imaging analysis to machine learning-based approaches.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1930851},
pmid = {42798843},
issn = {1663-4365},
abstract = {In vivo calcium imaging is a powerful technique for the monitoring activity of large neuronal populations in the intact brain. Two-photon microscopy provides subcellular resolution in head-fixed animals, and miniaturized fluorescence microscopy (miniscope) enables recordings of neuronal network activity in freely behaving animals. Combined with genetically encoded calcium indicators, these methods have revealed important new information about the functioning of neuronal circuits and enabled investigation of neuronal network dysfunction in mouse models of Alzheimer's disease. Typically, such imaging data are analyzed using event-based and statistical approaches, which have been highly informative but fail to capture the higher-order spatiotemporal structure of circuit activity. Here we propose that dimensionality reduction and neuronal manifold analysis, machine learning, and artificial intelligence (AI)-based methods provide powerful data-driven approaches, enabling feature extraction, detection of disease-associated network states, and simultaneous analysis of neural network activity and behavior. Crucially, beyond describing pathology, these approaches could offer a more sensitive and complementary readout for screening candidate therapeutic strategies in neurological disease models. Here, we summarize neuronal activity alterations identified across Alzheimer's disease mouse models using classical and AI-based calcium imaging analyses, and outline future perspectives for AI-driven approaches in this field, from interpretable architectures to multimodal integration of activity and behavior.},
}

@article {pmid42799322,
year = {2026},
author = {Valova, V and Cole, L and Rodriguez, NF and Braet, F and Johnstone, DM and Harwood, R},
title = {A validated deep learning workflow for 3D quantification of amyloid plaques in cleared mouse brain.},
journal = {Journal of microscopy},
volume = {},
number = {},
pages = {},
doi = {10.1111/jmi.70179},
pmid = {42799322},
issn = {1365-2818},
abstract = {Accurate quantification of amyloid plaque pathology is essential for understanding Alzheimer's disease (AD) progression and evaluating therapeutic interventions. Yet, conventional histology relies on sampling thin tissue sections and therefore incompletely captures three-dimensional (3D) plaque distributions, introducing bias and limiting scalability. Here, we present a validated and scalable 3D analysis pipeline for whole-brain quantification of amyloid plaques in cleared mouse brain tissue imaged by light-sheet microscopy. This pipeline also integrates deep learning-based segmentation with atlas registration to enable automated, region-specific quantification across intact brain volumes. Quantitative measurements obtained using this approach showed strong agreement with gold-standard stereology, while enabling higher throughput and comprehensive volumetric assessment of amyloid plaque burden. As a demonstration of its utility in a preclinical setting, we applied the pipeline to assess the neuroprotective effects of chronic saffron supplementation in APP/PS1 mice, identifying a significant reduction in hippocampal plaque load (p < 0.01). Together, these findings establish an accessible and validated framework for scalable 3D quantification of amyloid pathology, providing a platform for neuropathological phenotyping and therapeutic evaluation in preclinical AD research.},
}

@article {pmid42799385,
year = {2026},
author = {Söntgerath, M and Cutini, S and Thöne-Otto, AIT and Engel, A and Regenbrecht, F and Polyakova, M and Mueller, K and Scherf, N and Boehm, F and Anderl-Straub, S and Landwehrmeyer, B and Danek, A and Diehl-Schmid, J and Fassbender, K and Fliessbach, K and Jahn, H and Kornhuber, H and Lauer, M and Prudlo, J and Synofzik, M and Wiltfang, J and Otto, M and Schroeter, ML},
title = {Evaluating the correspondence of neuropsychological profiles with clinical diagnostic criteria for frontotemporal lobar degeneration and Alzheimer's disease: insights from k-means clustering.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1757680},
pmid = {42799385},
issn = {2813-3919},
abstract = {INTRODUCTION: Diagnosis of frontotemporal lobar degeneration (FTLD) is complicated by high heterogeneity within diagnostic groups and overlap between them. Using an unsupervised machine learning technique this study aimed to increase understanding of neuropsychological profiles in the spectrum of FTLD syndromes and to assess the consistency of these neuropsychological profiles with diagnostic criteria.

METHODS: Data from the German FTLD Consortium (FTLD-c) including behavioral variant of frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) syndromes, i.e., semantic variant (svPPA), and non-fluent variant (nfvPPA), healthy controls, and amnestic Alzheimer's disease (AD), and logopenic variant (lvPPA) was used. K-means clustering was applied on neuropsychological and behavioral data. Analysis was repeated for varying cluster numbers (k = 2-9). Resulting clusters were inspected on the correspondence with current diagnostic groups and neuropsychological profiles of the clusters were explored.

RESULTS: The results indicated that, based on neuropsychological profiles, particularly homogeneous clusters emerged for healthy controls, svPPA and bvFTD. In contrast, amnestic AD did not separate well from other diagnostic groups, and nfvPPA and lvPPA clustered together. Inspecting the neuropsychological profiles of the clusters showed that segregation of bvFTD from other patient groups was most supported by companion-rated questionnaires focused on behavior. Patients with svPPA showed impairment in both language and verbal memory tasks. LvPPA and nfvPPA showed impairment in processing speed as well as short term and working memory.

DISCUSSION: Using clustering this study provides insight into data-driven grouping of participants with FTLD based on neuropsychological deep-phenotyping. Whereas our approach confirmed svPPA and bvFTD to have comparatively homogeneous neuropsychological profiles, results suggest that the non-fluent PPA syndromes-lvPPA and nfvPPA-are difficult to segregate clinically, at least with the tests applied in our cohort. Our findings may suggest the need for further specification of clinical diagnostic criteria for these diseases.},
}

@article {pmid42799694,
year = {2026},
author = {Ye, X and Borges, K and Chang, M and Fu, X and Zhang, T},
title = {Recent advances in metabolism and applications of medium-chain triglycerides in neurodegenerative diseases.},
journal = {Critical reviews in food science and nutrition},
volume = {},
number = {},
pages = {1-13},
doi = {10.1080/10408398.2026.2737560},
pmid = {42799694},
issn = {1549-7852},
abstract = {Medium-chain triglycerides (MCTs) have attracted considerable interest in functional foods and nutrition due to their rapid and efficient metabolism. Emerging evidence indicates that MCTs can enhance cerebral energy metabolism, supporting interest in their potential role in nutritional strategies for neurodegenerative diseases and the maintenance of neurological function during healthy aging. This review examines the neuroprotective potential of MCTs from the perspectives of metabolism and application. It elucidates the distinctive metabolic pathways of MCTs, emphasizing their ability to supply alternative energy substrates to the brain through medium-chain fatty acids and ketone body production. Recent advances in chain-length-specific MCT formulations are also summarized, along with their applications in nutritional supplementation. Key challenges and future research directions are discussed, including further investigation into the chain-length-specific effects of MCTs, the need for standardized clinical validation, and rigorous safety assessment. Overall, current evidence suggests that MCT-based interventions can increase ketone availability and may improve selected metabolic or cognitive outcomes, suggesting potential relevance to maintaining functional healthspan, although clinical benefits remain inconsistent. These insights aim to inform future research and the development of MCT-based nutritional strategies for age-related diseases, particularly neurodegenerative diseases.},
}

@article {pmid42799832,
year = {2026},
author = {Hasan, A and Asfour, AAR and Qaba, H and Al-Sharabi, AA and Asfoor, A and Mohammed, S and Al-Adhreai, A and Güner, S and ALSaeedy, M},
title = {Mast Cells in Neuroimmune Interactions: Mechanisms, Pathophysiological Roles, and Therapeutic Implications.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42799832},
issn = {1559-1182},
mesh = {*Mast Cells/immunology/pathology/metabolism ; Humans ; Animals ; *Neuroimmunomodulation/physiology ; },
abstract = {Mast cells (MCs) are versatile immune cells that play a key role in neuroimmune interactions due to their strategic localization in barrier tissues and perineuronal sites, including the meninges, choroid plexus, thalamus, hypothalamus, and hippocampus within the central nervous system (CNS), as well as peripheral sites such as the skin, gastrointestinal tract, and dorsal root ganglia. They rapidly release stored and newly synthesized mediators, including histamine, tryptase, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), substance P, and prostaglandins, which regulate nerve signaling, vascular function, and inflammation. This review presents a framework integrating MC differentiation with distinct CNS microenvironments to explain their neuroprotective and toxic roles. The anatomical and molecular basis of MC-neuron interaction is discussed, with emphasis on bidirectional signaling via neuropeptides, neurotransmitters, and cytokines. MC functions in the CNS are highlighted, including neuroprotection through synaptic plasticity and BBB integrity under homeostatic conditions, as well as neurotoxicity, where aberrant activation promotes BBB breakdown, microglial priming, and neuroinflammatory cascades. Furthermore, the roles in which mast cell dysfunction is implicated in neurodegenerative and psychiatric disorders are examined, including Alzheimer's disease (AD), where amyloid-β triggers MC degranulation, Parkinson's disease (PD), where α-synuclein induces MC activation, multiple sclerosis (MS), autism, anxiety, and depression, as well as peripheral neuroimmune conditions affecting the skin, gut-brain axis, and pain. Current and emerging mast cell-targeted therapies, including stabilizers, histamine receptor blockers, tryptase inhibitors, and anti-IgE biologics, are discussed, along with future challenges in mast cell-based neuroimmunological treatment.},
}

*Mast Cells/immunology/pathology/metabolism
Humans
Animals
*Neuroimmunomodulation/physiology

@article {pmid42799937,
year = {2026},
author = {Giffard, J and Bindoff, AD and Roccati, E and Li, R and Vogel, AP and Goldberg, LR and Bai, Q and King, AE and Vickers, JC and Alty, J},
title = {Motor speech markers of Alzheimer's risk.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42799937},
issn = {2509-2723},
support = {2004051//National Health and Medical Research Council/ ; MRFF1170820//Medical Research Future Fund/ ; 116921//Royal Hobart Hospital Research Foundation/ ; FT220100253//Australian Research Council/ ; },
abstract = {Motor changes are increasingly recognized as part of the Alzheimer's disease (AD) phenotype, yet motor speech function and its clinical utility for early AD risk stratification remain underexplored. This cross-sectional study investigated whether measures of motor speech performance in home-based rapid syllable repetition (diadochokinesis [DDK]) tasks are associated with the established AD risk indicators of subjective cognitive decline (SCD), apolipoprotein E ε4 (APOE ε4) carriage, and plasma phosphorylated tau 181 (p-tau181). A community sample of 339 cognitively unimpaired adults (238 asymptomatic control (AC), 66.3 ± 6.5 years, 71.4% female; 101 SCD, 66.0 ± 6.6 years, 72.3% female) from the Island Study Linking Aging and Neurodegenerative Disease remotely self-administered four DDK tasks ("pa", "ta", "ka", "pataka") from the self-administered online Tasmanian Test protocol. Self-reported cognitive changes were used to classify AC or SCD groups. We conducted nonparametric analyses and percentile-LASSO multiple regression to predict risk indicators from motor speech performance measures, allowing for age, sex, education, anxiety, and depression. No nonparametric associations with SCD or APOE ε4 remained significant after adjustment for multiple comparisons. One measure of relative repetition variability remained significantly associated with plasma p-tau181. In covariate-adjusted regression analyses, motor speech measures were associated with SCD (AUC 0.700), APOE ε4 (AUC 0.715), and natural log-transformed p-tau181 (MAE 0.323). Sensitivity analyses for hearing loss, incomplete data, and depression-screened subsets revealed potentially mitigating effects of depression and blood biomarker data availability bias. This indicates that additional work, especially longitudinal follow-up, is needed to verify these preliminary findings in the search for scalable screening tools for preclinical dementia risk.},
}

@article {pmid42799938,
year = {2026},
author = {Diniz, GB and Schwartz, K and Erices, CT and Ott, SP and Griggs, DJ and Mendiola, JH and Sutphen, CL and Beckman, D and Register, TC and Hof, PR and Wilson, EN and Morrison, JH},
title = {Plasma and cerebrospinal fluid proteomics reveal distinct patterns of senescence and neuropathology in aging rhesus macaques.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42799938},
issn = {2509-2723},
support = {P51OD01110/NH/NIH HHS/United States ; R24AG07313/NH/NIH HHS/United States ; 3RF1NS121913-S1/NH/NIH HHS/United States ; P50AG047366/NH/NIH HHS/United States ; P30AG066515/NH/NIH HHS/United States ; P30AG072947/NH/NIH HHS/United States ; R24AG073199/NH/NIH HHS/United States ; R01AG087945/NH/NIH HHS/United States ; P30AG066514/NH/NIH HHS/United States ; K25AG086663/NH/NIH HHS/United States ; A25-0261/NH/NIH HHS/United States ; },
abstract = {Aging is the primary risk factor for neurodegenerative disease, yet the protein signatures that distinguish physiological brain aging from pathological decline remain incompletely defined in translational models. Using the targeted NULISAseq proteomic platform, we profiled cerebrospinal fluid (CSF) and plasma from 66 rhesus macaques (Macaca mulatta) spanning adult, pre-geriatric, and geriatric ages, and benchmarked the results against human reference samples. Age-related differences were broader and predominantly positive in plasma, whereas comparatively fewer CSF proteins differed with age. Canonical neurosenescence markers of axonal, astrocytic, and microglial biology, including neurofilaments, GFAP, and TREM2, showed age-related patterns similar to those reported in human aging. Synaptic and barrier proteins behaved differently by compartment: neuronal pentraxins and pleiotrophin were lower in the CSF of older animals, while choroid plexus proteins FOLR1 and IGFBP7 were lower in pre-geriatric animals. While immunohistochemistry confirmed extensive parenchymal amyloid deposition in geriatric brains alongside sparse tau pathology, plasma amyloid-beta and phosphorylated tau species tracked age and cortical amyloid burden more closely than their CSF counterparts. Systemic inflammatory and metabolic stress proteins, including IL6 and GDF15, were higher in older animals, resembling human inflammaging. Finally, we describe a subclustering of geriatric animals based on CSF proteomic signatures that is not explained by chronological age. Together, these results map compartment-specific signatures of senescence and early neuropathology across the non-human primate (NHP) lifespan and support the use of NHP models in translational biomarker studies.},
}

@article {pmid42799957,
year = {2026},
author = {Zhu, S and Liu, M and Chen, J and Zhou, L and Wang, R and Zhang, G},
title = {Long Non-Coding RNA PART1 in Alzheimer's Disease: Clinical Value and Improvement of Neurotoxicity and Apoptosis via miR-770-5p.},
journal = {Neurochemical research},
volume = {51},
number = {5},
pages = {},
pmid = {42799957},
issn = {1573-6903},
mesh = {Humans ; *Alzheimer Disease/metabolism/blood/genetics ; *MicroRNAs/metabolism/genetics ; *Apoptosis/physiology/drug effects ; *RNA, Long Noncoding/blood/genetics/metabolism ; Female ; Amyloid beta-Peptides/toxicity ; Male ; Aged ; Oxidative Stress/physiology ; Cell Line, Tumor ; Peptide Fragments/toxicity ; Cognitive Dysfunction/blood/metabolism ; Down-Regulation ; },
abstract = {Dysregulation of long non-coding RNA (lncRNA) PART1 is associated with neurodegenerative diseases, but its role in Alzheimer's disease (AD) remains unclear. This study investigated the clinical significance of PART1 in AD and its potential neuroprotective mechanisms, aiming to offer new insights for risk prediction and mechanism research. Serum PART1 levels were detected in 258 participants using real-time quantitative PCR (RT-qPCR), including 70 controls, 88 patients with amnestic mild cognitive impairment (aMCI), and 100 patients with AD. In vitro AD models were established using SH-SY5Y cells treated with amyloid-β peptide 25-35 (Aβ25-35). Functional assays were performed, including flow cytometry and Cell Counting Kit-8 (CCK-8) assay, along with the detection of oxidative stress levels. Mechanism studies included bioinformatic predictions and luciferase reporter assays. Serum PART1 was significantly downregulated in patients with aMCI and AD, and positively correlated with Mini-Mental State Examination scores. Low PART1 expression was a risk factor for AD and demonstrated good diagnostic value (AUC = 0.843). Aβ downregulated PART1 in SH-SY5Y cells, while PART1 overexpression attenuated Aβ-induced cytotoxicity, apoptosis, and oxidative stress. PART1 directly targeted and negatively regulated miR-770-5p, which was upregulated in AD. The neuroprotective effects of PART1 were reversed by miR-770-5p mimic. Furthermore, bioinformatic analysis and validation experiments identified GRIA2 as a downstream target of miR-770-5p. In summary, serum PART1 is a promising biomarker for AD. PART1 exerts neuroprotective effects against Aβ-induced damage by downregulating the miR-770-5p/GRIA2 axis, suggesting that PART1 is a potential target for intervention strategies in AD.},
}

Humans
*Alzheimer Disease/metabolism/blood/genetics
*MicroRNAs/metabolism/genetics
*Apoptosis/physiology/drug effects
*RNA, Long Noncoding/blood/genetics/metabolism
Female
Amyloid beta-Peptides/toxicity
Male
Aged
Oxidative Stress/physiology
Cell Line, Tumor
Peptide Fragments/toxicity
Cognitive Dysfunction/blood/metabolism
Down-Regulation

@article {pmid42799979,
year = {2026},
author = {Lifanov, DA and Perepelitsa, ES and Kopylova, AA and Blagova, AV and Salina, KO and Satish, A and Yurchenko, SO and Salmina, AB and Illarioshkin, SN},
title = {Generation of Vascular Organoids from Human iPSCs to Study Neurodegenerative Processes.},
journal = {Bulletin of experimental biology and medicine},
volume = {},
number = {},
pages = {},
pmid = {42799979},
issn = {1573-8221},
abstract = {Organoids are a type of three-dimensional cellular constructs comprising cells of various specializations (phenotypes). In contrast to simple cellular spheroids (aggregates), cells within organoids exhibit more complex differentiation and functional characteristics. This study describes a protocol for generating vascular organoids incorporating vascular endothelial cells. A step-by-step workflow is presented, detailing the necessary reagents and consumables. Additionally, a method for validating differentiation outcomes using immunofluorescence staining is described. Morphological differences are reported between organoids derived from stem cells of a healthy donor and those from patients with Alzheimer's or Parkinson's disease.},
}

@article {pmid42800026,
year = {2026},
author = {Yu, X and Ren, Q and Gao, Y and Xie, S and Dang, R and Meng, J and Su, Z and Li, M and Ao, Y and Liu, A and Wang, Y and Xie, W},
title = {Activation of TREM2 via single-domain antibodies improves synaptic and cognitive function in 5×FAD mice.},
journal = {Cell reports},
volume = {45},
number = {10},
pages = {118063},
doi = {10.1016/j.celrep.2026.118063},
pmid = {42800026},
issn = {2211-1247},
abstract = {Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, and dysfunction of triggering receptor expressed on myeloid cells 2 (TREM2) in microglia increases AD risk. TREM2 activation promotes protective microglial functions and mitigates AD pathology. Although TREM2-activating antibodies show therapeutic potential, the mechanisms underlying TREM2-mediated rescue effects remain unclear. Here, we show that two TREM2-activating single-domain antibodies (sdAbs), 10C11 and 10E12, activate microglia and rescue cognitive deficits in early-stage transgenic mice with five familial Alzheimer's disease mutations (5×FAD) following ventral hippocampal injection. 10E12 reduces Aβ plaques and preserves synaptic function, whereas 10C11 protects synapses without affecting plaque burden. Both antibodies reduce C1q levels in AD model mice, suggesting that TREM2 activation exerts multifaceted functions in AD. Together, this study presents two TREM2-targeting sdAbs with AD therapeutic potential and provides insights into the cellular mechanisms underlying TREM2 activation and microglial modulation.},
}

@article {pmid42800042,
year = {2026},
author = {Ho, BL and Yang, YH},
title = {Blood-based biomarkers in the anti-amyloid era of Alzheimer's disease: clinical utility, implementation challenges, and future directions.},
journal = {Neurodegenerative disease management},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17582024.2026.2734618},
pmid = {42800042},
issn = {1758-2032},
abstract = {BACKGROUND: Implementation of disease-modifying anti-amyloid therapies for Alzheimer's disease remains constrained by the cost and procedural burden of positron emission tomography and cerebrospinal fluid testing. This review evaluates blood-based biomarkers in therapeutic pathways.

METHODS: PubMed/MEDLINE and Embase were searched for literature published from January 2018 onward, with earlier landmark studies included when relevant. Evidence was synthesized on plasma biomarkers in treatment eligibility, biological staging, longitudinal monitoring, therapeutic response, and risk stratification for amyloid-related imaging abnormalities.

RESULTS: Among assays, plasma p-tau217 consistently demonstrates the highest diagnostic accuracy for detecting cortical amyloid pathology across clinical settings. The plasma p-tau217/Aβ1-42 ratio is the first blood-based assay cleared by the FDA to identify amyloid pathology, supporting clinical triage. Complementary biomarkers, including plasma Aβ42/40, glial fibrillary acidic protein, and neurofilament light chain, reflect amyloid burden, astroglial activation, and neurodegeneration. Clinical adoption remains limited by inter-assay variability, inconsistent diagnostic thresholds, and the lack of surrogate endpoints for treatment monitoring and adverse-event assessment.

CONCLUSIONS: Blood-based biomarkers are best incorporated into structured, stepwise diagnostic and therapeutic frameworks rather than replacing established reference standards. Progress will require assay harmonization, prospective validation, and interpretable biomarker-guided care pathways to support scalable, safe implementation of disease-modifying therapies in routine dementia care.},
}

@article {pmid42800170,
year = {2026},
author = {Yang, S and Guo, B and Deng, D and Zhang, Y and Zhou, Q},
title = {Ketamine metabolite HNK ameliorates anhedonia symptom in Alzheimer's disease mice.},
journal = {Biochemical and biophysical research communications},
volume = {838},
number = {},
pages = {154535},
doi = {10.1016/j.bbrc.2026.154535},
pmid = {42800170},
issn = {1090-2104},
abstract = {Anhedonia is frequently observed in Alzheimer's disease (AD) patients and is associated with a higher risk of cognitive decline and dementia, and it potentially serve as preclinical marker and psychopathological risk factor for AD. Current antidepressants show limited efficacy in anhedonia, highlighting a critical unmet medical need. In this study, APP/PS1 mice at 8 months of age exhibited pronounced anhedonia symptom, as assessed by the sucrose preference tests. Strikingly, a single dose of the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) rapidly alleviated this symptom. Mechanistically, HNK increased the prefrontal excitatory/inhibitory (E/I) ratio via enhanced activity in the excitatory neurons, accompanied by reduced phosphorylated eEF2 levels and elevated BDNF and GLT-1 expression. These findings indicate that HNK ameliorates anhedonia in AD mice via mechanisms similar to those shown in standalone depression, and hence offers a promising therapeutic intervention worthy of further pursuing.},
}

@article {pmid42800174,
year = {2026},
author = {Yang, S and Wu, D and Li, Y and Ding, Y},
title = {Microglial FKBP51 drives immunometabolic dysfunction linking perioperative neurocognitive disorders and Alzheimer's disease.},
journal = {Biochemical and biophysical research communications},
volume = {838},
number = {},
pages = {154628},
doi = {10.1016/j.bbrc.2026.154628},
pmid = {42800174},
issn = {1090-2104},
abstract = {BACKGROUND: Perioperative neurocognitive disorders (PND) and Alzheimer's disease (AD) are both important aging related cognitive disorders. Accumulating evidence suggests that they share common pathological mechanisms involving Aβ deposition, neuroinflammation, and immunometabolic imbalance. However, the key regulatory molecules linking these two conditions remain unclear. FKBP prolyl isomerase 51 (FKBP51) is an immune regulatory molecule widely involved in inflammation control and metabolic homeostasis maintenance, but its role in PND and AD is still unknown. This study aimed to investigate whether FKBP51 participates in the shared pathological processes of PND and AD by regulating microglial immunometabolism.

METHODS: This study integrated transcriptomic data from PND and AD brain tissues to screen for commonly abnormally expressed metabolism related genes and analyzed key hub genes in relation to clinical cognitive scores. The Brain RNA-seq database, single cell RNA sequencing data, and immunofluorescence staining were used to determine the cellular localization and expression characteristics of FKBP51. Primary microglia were stimulated with oligomeric Aβ42, and Fkbp5 expression was knocked down using siRNA to evaluate its effects on microglial inflammatory responses and Aβ phagocytosis. Furthermore, single gene GSEA, Seahorse metabolic analysis, and ROS and JC-1 detection were combined to investigate the regulatory role of FKBP51 on microglial mitochondrial function and oxidative phosphorylation.

RESULTS: Bioinformatics analysis identified FKBP51 as a key metabolism related hub gene that was commonly abnormally elevated in both PND and AD brain tissues, and its expression level was significantly correlated with cognitive decline in AD patients. Further studies revealed that FKBP51 was enriched in microglia and was significantly upregulated in brain tissues from AD patients and model mice. Aβ42 stimulation markedly induced FKBP51 expression in microglia. Functional experiments demonstrated that Fkbp5 knockdown enhanced microglial phagocytic capacity for Aβ and reduced the expression and secretion of proinflammatory factors. Mechanistic studies showed that FKBP51 was closely associated with pathways related to fatty acid oxidation and oxidative phosphorylation. Following FKBP51 inhibition, maximal respiration capacity and ATP production in microglia were significantly increased, mitochondrial membrane potential was improved, and ROS accumulation was markedly reduced. These metabolic improvements were accompanied by restoration of microglial phagocytic function and alleviation of the inflammatory state.

CONCLUSIONS: This study reveals that FKBP51 is an important immunometabolic regulatory molecule linking the shared pathological processes of PND and AD. Abnormal upregulation of FKBP51 promotes microglial functional imbalance by inhibiting mitochondrial oxidative phosphorylation and inducing oxidative stress, thereby exacerbating Aβ related neuroinflammation and cognitive impairment. Targeting FKBP51 mediated microglial metabolic reprogramming may provide a novel intervention strategy for aging related cognitive disorders such as PND and AD.},
}

@article {pmid42800202,
year = {2026},
author = {Liang, PW and Yu, RL and Hong, WP and Sung, PS and Tan, CH},
title = {Disease-specific roles of multidimensional apathy in linking cognitive and social functioning across neurodegenerative diseases.},
journal = {Parkinsonism & related disorders},
volume = {152},
number = {},
pages = {108997},
doi = {10.1016/j.parkreldis.2026.108997},
pmid = {42800202},
issn = {1873-5126},
abstract = {BACKGROUND: Apathy is a multidimensional neuropsychiatric syndrome involving cognitive, emotional, and behavioral domains. Cognitive impairment and apathy are both associated with reduced social functioning, but how specific apathy dimensions relate cognition to social functioning across neurodegenerative diseases remains unclear.

OBJECTIVE: This study compared multidimensional apathy profiles across Parkinson's disease (PD), Alzheimer's disease-like mild cognitive impairment (AD-like MCI), and normal controls (NC), and investigated whether specific apathy dimensions mediate the association between cognitive function and social functioning.

METHODS: A total of 297 participants were enrolled, comprising 96 PD, 66 AD-like MCI, and 135 NC. All participants provided demographic information and underwent neuropsychological tests, a multidimensional apathy measure, and a social functioning measure. Depressive symptoms, sex, age, and education were included as covariates. Mediation analyses were conducted using PROCESS Model 4 with bootstrapping.

RESULTS: A coherent triadic association among cognitive function, apathy, and social functioning was observed exclusively in the PD group. Hierarchical regression showed that cognitive and social motivation (CSM) independently predicted social functioning beyond executive function and covariates. Mediation analysis demonstrated that mental shifting was indirectly associated with social functioning through CSM (indirect effect = -.014, 95% CI [-.033, -.002]), with a non-significant direct effect. This pattern was not observed in the AD-like MCI or NC groups.

CONCLUSIONS: These findings reveal a PD-specific pattern of associations among impaired mental shifting, CSM, and reduced social functioning. Its absence in AD-like MCI suggests distinct apathy mechanisms across neurodegenerative diseases and highlights CSM as a potential intervention target.},
}

@article {pmid42800281,
year = {2026},
author = {Alhasan, AS and Alhasan, MS and Milburn, J and Ghunaim, HA and Khalil, M and Almaghraby, A and Alharthi, O and Hamoud, S and Essibayi, MA and Elhassan, YH and Feltrin, F and Singh, S and Lakhani, DA and Azzam, AY},
title = {Sex composition and FDG-PET prediction of Alzheimer's disease conversion: response to Rudroff.},
journal = {The journal of nutrition, health & aging},
volume = {30},
number = {10},
pages = {100988},
doi = {10.1016/j.jnha.2026.100988},
pmid = {42800281},
issn = {1760-4788},
}

@article {pmid42788140,
year = {2026},
author = {Eldehna, WM and El-Damasy, AK and Lim, J and Hewala, MM and Elsayed, ZM and Al-Warhi, T and El-Hamaky, AA and Paik, MJ and Keum, G and Elnagar, MR and Kim, H and Tawfik, HO},
title = {Discovery of tricyclic benzo[4,5]imidazo[2,1-b]thiazole-3-hydroxyindolin-2-one hybrids as selective MAO-B and cholinesterase inhibitors.},
journal = {RSC advances},
volume = {},
number = {},
pages = {},
pmid = {42788140},
issn = {2046-2069},
abstract = {A series of 13 novel 3-hydroxyindolin-2-one-benzo[4,5]imidazo[2,1-b]thiazole hybrids was designed, synthesized, and evaluated as potential anti-Alzheimer agents targeting monoamine oxidase B (MAO-B) and cholinesterases. The target compounds were obtained by condensing a benzo[4,5]imidazo[2,1-b]thiazole-based ketone with substituted and N-alkylated isatins and were structurally confirmed by [1]H NMR, [13]C NMR, and elemental analysis. All synthesized compounds were screened for their inhibitory activities against MAO-A and MAO-B enzymes. Most derivatives displayed weak MAO-A inhibition while exhibiting a marked preference for MAO-B inhibition. Among them, compounds 6c and 6b emerged as the most potent MAO-B inhibitors, with IC50 values of 0.90 ± 0.005 and 0.97 ± 0.010 µM, respectively. Structure-activity relationship studies revealed that substitution at the C-5 position of the isatin ring, particularly with halogen atoms, significantly enhanced MAO-B inhibitory activity, whereas N-alkylation generally reduced both potency and selectivity. Based on their superior MAO-B inhibitory profiles, compounds 6b and 6c were further evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Notably, compound 6c exhibited potent dual cholinesterase inhibition, showing AChE inhibitory activity comparable to that of donepezil and superior BuChE inhibition. Furthermore, SwissADME analysis indicated favorable drug-likeness properties for the most active compounds. Molecular docking studies demonstrated favorable binding interactions of the lead compounds within the active sites of MAO-B and AChE, while a 200 ns molecular dynamics simulation confirmed the stability of the MAO-B-6c complex. Collectively, these findings identify 6c as a promising multitarget lead compound combining selective MAO-B inhibition with potent cholinesterase inhibitory activity and highlight the 3-hydroxyindolin-2-one-benzo[4,5]imidazo[2,1-b]thiazole scaffold as a valuable platform for the development of novel therapeutic agents for Alzheimer's disease.},
}

@article {pmid42788819,
year = {2026},
author = {Busquets, MA and Sabaté, R and Álvarez-Berbel, I and Espargaró, A},
title = {Applications of Prussian blue nanoparticles in the treatment of neurodegenerative diseases.},
journal = {Nanomedicine (London, England)},
volume = {},
number = {},
pages = {1-18},
doi = {10.1080/17435889.2026.2734070},
pmid = {42788819},
issn = {1748-6963},
abstract = {Neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, are characterized by progressive neuronal dysfunction associated with oxidative stress, chronic neuroinflammation, mitochondrial impairment, and pathological protein aggregation. Despite advances in symptomatic treatments, effective disease-modifying therapies remain limited. This review examines the emerging role of Prussian blue nanoparticles (PBNPs) as multifunctional nanoplatforms for neurodegenerative diseases and related neurological conditions, including ischemic stroke and nerve regeneration. Their intrinsic enzyme-mimetic (nanozyme) activities enable the catalytic scavenging of reactive oxygen and nitrogen species, mimicking key antioxidant enzymes such as superoxide dismutase and catalase. PBNPs may also modulate neuroinflammation, microglial activation, and the aggregation of neurotoxic proteins, including β-amyloid and α-synuclein. Advances in nanoparticle engineering to improve brain delivery, targeting, and pharmacokinetics are highlighted. Finally, the review critically addresses toxicological challenges, including biodistribution, organ accumulation, degradation, long-term persistence, and the potential effects of surface modifications, which remain key considerations for the safe clinical translation of PBNP-based therapeutic and theranostic strategies.},
}

@article {pmid42789105,
year = {2026},
author = {Godinho, WDN and Filho, FSLV and Amaral, CML and Guedes, MIF and de Serpa, GL and Loureiro, ACC and Ceccatto, VM and Soares, PM},
title = {High-intensity interval training modulates APP expression and reduces neuronal apoptosis in a β-amyloid-induced model of Alzheimer's disease: hippocampal evidence.},
journal = {Experimental brain research},
volume = {244},
number = {11},
pages = {},
pmid = {42789105},
issn = {1432-1106},
mesh = {Animals ; Male ; *Alzheimer Disease/metabolism/chemically induced/pathology/therapy ; *Apoptosis/physiology ; Rats, Wistar ; *Hippocampus/metabolism/pathology ; Amyloid beta-Peptides/toxicity ; Disease Models, Animal ; Rats ; *High-Intensity Interval Training/methods ; *Amyloid beta-Protein Precursor/metabolism ; *Neurons/metabolism/pathology ; Peptide Fragments/toxicity ; Maze Learning/physiology ; Fibronectins ; },
abstract = {High-intensity interval training (HIIT) has emerged as a promising non-pharmacological strategy for neuroprotection, although its molecular effects in Alzheimer's disease (AD) remain unclear. This study investigated the effects of HIIT on gene expression (FNDC5, PPARGC1A, APP), protein expression, cognitive performance, and neuronal apoptosis in a β-amyloid-induced rat model of AD. Sixty male Wistar rats were divided into four groups: sham sedentary (SS), sham trained (ST), Alzheimer sedentary (AS), and Alzheimer trained (AT). AD-like pathology was induced by intrahippocampal infusion of β-amyloid (Aβ1-42). Animals underwent an 8-week HIIT protocol. Gene expression was assessed by qPCR using the ΔCt method, and statistical analyses were performed using two-way ANOVA or mixed-design ANOVA followed by Tukey's post hoc test. HIIT significantly increased PPARGC1A expression (p < 0.05), while FNDC5 gene expression remained unchanged (p > 0.05). However, FNDC5 protein expression was increased in trained groups. APP gene expression was significantly reduced at the transcriptional level (p < 0.05), whereas APP protein abundance differed among experimental conditions without a uniform training-related reduction. HIIT improved physical performance (p < 0.0001) and reduced hippocampal neuronal apoptosis (p < 0.05). In the Morris water maze, improvement was observed only within the Alzheimer-trained group, with no significant differences between groups. HIIT was associated with molecular and cellular adaptations consistent with a neuroprotective response in this β-amyloid-induced model, including metabolic-pathway modulation, reduced APP transcription, and attenuated neuronal apoptosis. These effects were not accompanied by robust between-group cognitive improvement.},
}

Animals
Male
*Alzheimer Disease/metabolism/chemically induced/pathology/therapy
*Apoptosis/physiology
Rats, Wistar
*Hippocampus/metabolism/pathology
Amyloid beta-Peptides/toxicity
Disease Models, Animal
Rats
*High-Intensity Interval Training/methods
*Amyloid beta-Protein Precursor/metabolism
*Neurons/metabolism/pathology
Peptide Fragments/toxicity
Maze Learning/physiology
Fibronectins

@article {pmid42789112,
year = {2026},
author = {McCann, E and Coleman, F and Lee, S and Fazlollahi, A and O'Sullivan, JD and Nestor, PJ},
title = {Dorsal and ventral stream visuoperceptual processing deficits in Lewy body disease.},
journal = {Journal of neurology},
volume = {273},
number = {10},
pages = {},
pmid = {42789112},
issn = {1432-1459},
support = {Start-up package from UQ//Queensland Brain Institute/ ; Mater Misericordiae Limited//Queensland Brain Institute/ ; Research Training Program Recipient//Australian Government Department of Education/ ; },
mesh = {Humans ; *Lewy Body Disease/complications/physiopathology/psychology ; Female ; Neuropsychological Tests ; Male ; Aged ; *Visual Perception/physiology ; Attention/physiology ; Aged, 80 and over ; *Perceptual Disorders/etiology ; Executive Function/physiology ; Alzheimer Disease/physiopathology/complications ; Middle Aged ; Hallucinations/etiology/physiopathology ; Visual Pathways/physiopathology ; },
abstract = {INTRODUCTION: Hypometabolism of visual-processing cortices is the hallmark of dementia in Lewy body diseases (LBD) yet visuoperceptual impairments remain under-researched compared to other cognitive domains.

METHODS: Novel, sensitive measures of dorsal- and ventral-stream visual processing were developed and administered to n=53 LBD patients, spanning cognitively asymptomatic to dementia, and compared to n=29 Alzheimer's disease (AD) patients. Further analyses stratified LBD for visual hallucination status and contrasted visuoperceptual performance to measures of attention/executive function.

RESULTS: Visuoperceptual impairments were more prominent in LBD than AD, being detectable even in some that were cognitively asymptomatic. LBD demonstrated comparable ventral and dorsal impairments, whereas ventral visuoperceptual performance was relatively preserved compared to dorsal in AD. In LBD, visuoperceptual impairments were strongly associated with visual hallucination and explained a significant amount of performance on visually presented executive function/attention measures. The effect sizes of impairment in demented LBD were substantially larger on the novel visuoperceptual tests compared to standard non-visually presented tests of attention (Digit Span) and executive function (phonemic fluency).

DISCUSSION: Early dorsal and ventral stream impairments are a hallmark of dementia in LBD, differing quantitatively and qualitatively from AD. These deficits in LBD were more pronounced than those of attention and executive function.},
}

Humans
*Lewy Body Disease/complications/physiopathology/psychology
Female
Neuropsychological Tests
Male
Aged
*Visual Perception/physiology
Attention/physiology
Aged, 80 and over
*Perceptual Disorders/etiology
Executive Function/physiology
Alzheimer Disease/physiopathology/complications
Middle Aged
Hallucinations/etiology/physiopathology
Visual Pathways/physiopathology

@article {pmid42789205,
year = {2026},
author = {Fakorede, S and Lateef, OM and Udefa, AL and Ajagbe, AO and Roy, S and Akosile, PO and Awobona, TA and Anyanwu, GE},
title = {The Interplay of Metabolic Dysfunction, Neuroinflammation, and Mitochondrial Dysfunction in Balance Impairment: Insights from Type 2 Diabetes Mellitus and Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42789205},
issn = {1559-1182},
mesh = {Humans ; Animals ; *Mitochondria/metabolism/pathology ; *Diabetes Mellitus, Type 2/metabolism/physiopathology/complications ; *Alzheimer Disease/metabolism/physiopathology/complications/pathology ; *Neuroinflammatory Diseases/metabolism/physiopathology/pathology/complications ; *Postural Balance/physiology ; Inflammation ; },
abstract = {Balance impairment and postural instability represent critical challenges for the aging population, serving as primary precursors to falls and functional decline in individuals with Type 2 Diabetes Mellitus. While traditional clinical models have largely separated these conditions, attributing balance loss in T2DM to peripheral neuropathy and in AD to central cortical atrophy, mounting evidence suggests a convergence of multi-system impairments driven by a shared central pathophysiology. This narrative review proposes an integrative framework centered on a vicious, self-reinforcing cycle involving metabolic dysfunction, chronic neuroinflammation, and mitochondrial failure as the core mechanistic link driving balance impairment. We detail how systemic and cerebral insulin resistance, coupled with glucotoxicity, trigger the activation of the NLRP3 inflammasome and the subsequent release of pro-inflammatory cytokines. This inflammatory environment exacerbates mitochondrial bioenergetic failure and oxidative stress, selectively targeting high-energy motor circuits such as the striatum and basal ganglia while simultaneously contributing to musculoskeletal sarcopenia and peripheral nerve demyelination. By synthesizing the intricate interplay between these molecular pathways, this review moves beyond disease-specific silos to offer a novel perspective on the shared pathophysiology of postural instability. Furthermore, we explore the therapeutic potential of metabolic modulators, such as GLP-1 receptor agonists, and mitochondrial-targeted antioxidants, alongside multimodal rehabilitation strategies. Ultimately, this unified model provides a foundation for developing precision-based interventions to mitigate fall risk and preserve functional independence in vulnerable aging populations.},
}

Humans
Animals
*Mitochondria/metabolism/pathology
*Diabetes Mellitus, Type 2/metabolism/physiopathology/complications
*Alzheimer Disease/metabolism/physiopathology/complications/pathology
*Neuroinflammatory Diseases/metabolism/physiopathology/pathology/complications
*Postural Balance/physiology
Inflammation

@article {pmid42789261,
year = {2026},
author = {Poimenova, IA and Mikheev, IV and Manuilenko, VA and Proskurnina, EV and Proskurnin, MA},
title = {Vibrational Spectroscopy in Alzheimer's Disease Research and Diagnostics: From Molecular Biomarkers to Spectral Fingerprints.},
journal = {Critical reviews in analytical chemistry},
volume = {},
number = {},
pages = {1-22},
doi = {10.1080/10408347.2026.2738019},
pmid = {42789261},
issn = {1547-6510},
abstract = {Alzheimer's disease (AD) research is increasingly shaped by biologically anchored criteria and blood-based biomarker workflows, but the role of vibrational spectroscopy within this landscape remains difficult to define because infrared (IR), Raman, and surface-enhanced Raman scattering (SERS) methods measure different chemical information and are often validated in different matrices. This review critically evaluates IR-, Raman-, and SERS-based approaches to AD biomarker research from an analytical-chemistry perspective. The review distinguishes clinically anchored biomarkers, including amyloid-β-related measures and phosphorylated tau species, from exploratory spectroscopic readouts such as β-sheet enrichment, amyloid aggregation state, and multicomponent biochemical fingerprints. We compare relevant spectral regions, sample-matrix compatibility, detection limits, sample preparation, assay formats, and integration with chemometrics and machine learning. Current evidence indicates IR-based methods are most mature as structural and compositional Странные точки между словами на скриншоте tools, whereas spontaneous Raman spectroscopy is mainly used for rapid spectral fingerprinting of biosamples. SERS expands Raman analysis toward low-abundance AD-related analytes through plasmonic substrates, nanotags, lateral-flow formats, and immuno- or aptamer-assisted recognition. Machine learning models improve classification but require donor-level splitting, and molecular anchoring of discriminative features. Overall, vibrational spectroscopy should be positioned as a complementary platform for biochemical phenotyping and orthogonal molecular readout development.},
}

@article {pmid42789386,
year = {2026},
author = {Patai, EZ and Stawarczyk, D and Herweg, N and Gomes, CA and Zhang, H and Schulze-Bonhage, A and Kunz, L and Axmacher, N},
title = {Navigation strategies predict spatial memory and hippocampal recruitment.},
journal = {Cell reports},
volume = {45},
number = {10},
pages = {117971},
doi = {10.1016/j.celrep.2026.117971},
pmid = {42789386},
issn = {2211-1247},
abstract = {Navigation in the real world may rely on a multitude of strategies with distinct advantages and disadvantages; however, the characterization of spontaneous strategy use is scarce. We explore data across three groups engaged in virtual navigation: patients with epilepsy undergoing invasive electrophysiological recordings, two groups undergoing fMRI scanning: young adults at genetic risk for Alzheimer's disease (APOE-ε4 carriers), and healthy controls. We establish metrics to quantitatively characterize participants' trajectories, reflecting putative strategies: straightness, deviation to boundary, and overlap of paths. We find that strategy use is variable within participant, changes across the experiment, and is adaptive in a group-dependent manner. While hippocampal blood-oxygen dependent (BOLD) activity and theta power are generally inversely related, hippocampal recruitment is both group- and strategy specific. Our results underscore the idiosyncratic nature of spatial navigation by revealing how these behaviors are altered by disease, the subsequent compensatory neural dynamics, and the link between mesoscopic and macroscopic neural signals.},
}

@article {pmid42789462,
year = {2026},
author = {Fresnais, D and Fure, B},
title = {Anxiety Symptoms and Risk of Dementia Progression in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.},
journal = {Dementia and geriatric cognitive disorders},
volume = {},
number = {},
pages = {1},
doi = {10.1159/dem/aciag007},
pmid = {42789462},
issn = {1421-9824},
abstract = {INTRODUCTION: Anxiety is among the earliest and most common neuropsychiatric symptoms in cognitive impairment. Emerging evidence suggests that anxiety may elevate the risk of cognitive decline in mild cognitive impairment (MCI). This systematic review and meta-analysis was performed to quantitatively synthesize evidence from cohort studies on the association between anxiety symptoms and dementia conversion in MCI.

METHODS: A systematic literature search was performed in Medline and other relevant databases to find cohort studies examining the association between anxiety symptoms and dementia progression in MCI.

RESULTS: Fifteen cohort studies were included in the systematic review, of which fourteen were included in meta-analyses. Anxiety was significantly associated with an increased risk of all cause dementia, HR = 1.25; 95% CI, 1.11-1.41; p < 0.001, and Alzheimer's disease, HR = 1.32; 95% CI, 1.16-1.49; p < 0.001, while pooled odds ratios did not show a significant association OR = 1.15; 95% CI, 0.84-1.57; p = 0.39.

CONCLUSION: Anxiety symptoms may be associated with an elevated risk of dementia conversion in MCI. Further large-scale prospective cohort studies are needed to determine the strength and clinical importance of these findings.},
}

@article {pmid42789572,
year = {2026},
author = {Ranjan, R and Kawnayn, G and Yusuf, MA and Uddin, MN and Mamun, MT and Al Mamun, A and Hossain, S and Hassan, MS and Imtiaz, N and Hakim, M},
title = {Age at dementia diagnosis, subtype associations, and neuroimaging differentiation in Bangladesh: The CARED study.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0359109},
doi = {10.1371/journal.pone.0359109},
pmid = {42789572},
issn = {1932-6203},
mesh = {Humans ; Bangladesh/epidemiology ; Male ; Female ; Cross-Sectional Studies ; *Neuroimaging/methods ; Aged ; *Dementia/diagnostic imaging/diagnosis/classification/epidemiology ; Middle Aged ; *Alzheimer Disease/diagnostic imaging/diagnosis/epidemiology ; Dementia, Vascular/diagnostic imaging ; ROC Curve ; Magnetic Resonance Imaging ; Brain/diagnostic imaging ; Age Factors ; },
abstract = {BACKGROUND: Evidence on age at diagnosis of dementia and differentiation of dementia subtypes in Bangladesh is limited. This study aimed to determine age at diagnosis, examine factors associated with dementia subtypes, and evaluate the discriminatory utility of neuroimaging scales in a Bangladeshi clinical population.

METHODS: The Community Awareness and Research on Early Dementia (CARED) study was a cross-sectional observational study conducted 2019-2024 at a tertiary care centre in Bangladesh. A total of 658 adults presenting with cognitive impairment, undergoing evaluation for suspected dementia were included. Diagnoses were established using DSM-5 criteria by a multidisciplinary team. Patients were categorized into dementia subtypes. Pseudodementia was retained as separate comparator group. Multivariable regression analyses were performed to identify factors associated with dementia subtypes. Receiver operating characteristic (ROC) curve analyses were used to assess the discriminatory performance of neuroimaging scales.

RESULTS: Among 658 patients, Alzheimer's-related dementia (ARD) accounted for 51.7% of cases. The mean age at diagnosis was significantly higher in ARD compared with non-Alzheimer's-related dementia (nARD) (67.7 ± 10.8 vs 64.3 ± 11.4 years, P < 0.001). In multivariable analysis, nARD was associated with an earlier age at diagnosis by 4.3 years compared with ARD. Vascular dementia was associated with hypertension, OR 4.2 (95% CI 1.1-16.6), P = 0.04, and smoking, OR 13.1 (95% CI 1.6-103.3), P = 0.01. Neuroimaging scales demonstrated variable discriminatory performance. Medial temporal atrophy showed good discrimination for ARD (AUROC 0.752), while Fazekas scores demonstrated good performance for vascular dementia (AUROC 0.838) and mixed dementia (AUROC 0.836). Global cortical atrophy showed moderate discriminatory ability for frontotemporal dementia (AUROC 0.659).

CONCLUSIONS: Age at diagnosis varied across dementia subtypes in this Bangladeshi clinical cohort, with non-Alzheimer's diagnosed earlier than Alzheimer's. Structured MRI visual rating scales showed variable subtype-specific discriminatory performance, suggesting that they may provide adjunctive information for dementia subtype differentiation when interpreted alongside multidisciplinary clinical assessment.},
}

Humans
Bangladesh/epidemiology
Male
Female
Cross-Sectional Studies
*Neuroimaging/methods
Aged
*Dementia/diagnostic imaging/diagnosis/classification/epidemiology
Middle Aged
*Alzheimer Disease/diagnostic imaging/diagnosis/epidemiology
Dementia, Vascular/diagnostic imaging
ROC Curve
Magnetic Resonance Imaging
Brain/diagnostic imaging
Age Factors

@article {pmid42789798,
year = {2026},
author = {Reina-Gonzalez, P and Anchan, A and Bekos, J and Abu-Salah, A and Sarkar, S},
title = {Novel Targets and Treatments for Neurodegenerative Diseases Revealed by Drosophila.},
journal = {Annual review of pharmacology and toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-pharmtox-060325-064705},
pmid = {42789798},
issn = {1545-4304},
abstract = {Neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, and others lack any disease-modifying therapy due to the lack of mechanistic understanding of the disease etiology. The genetic tractability, short lifespan, and conserved cellular biology of Drosophila melanogaster have positioned the fly as a powerful model organism for a pathway-driven therapeutic discovery across NDDs. Fly models expressing human pathogenic proteins, including Aβ, tau, α-synuclein, and others, recapitulate core features of these NDDs such as proteostasis defects, RNA dysregulation, mitochondrial dysfunction, lipid signaling abnormalities, and innate immune activation. Unbiased genetic and pharmacologic screens in these systems have identified conserved therapeutic nodes such as PARP signaling and insulin/IGF pathways. In this review, we discuss these advances to define conserved therapeutic axes identified in Drosophila and evaluate their translational potential for neurodegenerative disorders.},
}

@article {pmid42790169,
year = {2026},
author = {Zhang, B and Nan, J and Zhang, Y and Zhang, B and Ke, C and Wang, W and Wu, T and Xia, J and Yang, F and He, M and Tian, L and Yang, Z and Liang, C},
title = {Phytocannabinoid cannabidiol (CBD) in neurodegenerative diseases: From polypharmacology to drug development.},
journal = {European journal of medicinal chemistry},
volume = {320},
number = {},
pages = {119360},
doi = {10.1016/j.ejmech.2026.119360},
pmid = {42790169},
issn = {1768-3254},
abstract = {Cannabidiol (CBD) is a non-intoxicating phytocannabinoid that has attracted interest as a multi-target neurotherapeutic candidate for neurodegenerative diseases. CBD is a lipophilic terpenophenolic chemotype whose phenolic redox chemistry, membrane partitioning, cytochrome P450-mediated metabolism, and formulation-dependent exposure are central to its biological activity and translational limitations. In addition, CBD engages a broad target network relevant to neurodegeneration. Major components include cannabinoid receptors, transient receptor potential channels, peroxisome proliferator-activated receptor-γ, adenosine and serotonin signaling systems, voltage-gated calcium channels, and redox-regulatory pathways. These mechanisms converge on neuroinflammation, excitotoxicity, mitochondrial dysfunction, impaired proteostasis, and synaptic injury. Preclinical studies across models of Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis consistently support CBD's anti-inflammatory, antioxidant, mitochondria-protective, and neuroprotective pharmacology. The magnitude of these effects depends on dose, treatment timing, model system, and route of administration. Clinical evidence remains preliminary and is mainly symptomatic, with signals in agitation, sleep disturbance, spasticity, quality of life, and neuropsychiatric symptoms rather than proven disease modification. Key barriers to development include low and variable oral bioavailability, incomplete brain exposure data, uncertain active metabolite contributions, limited target-engagement biomarkers, and insufficient exposure-response definition. Future development of CBD and optimized cannabinoid-derived analogues will require medicinal chemistry strategies to improve potency, selectivity, metabolic stability, CNS exposure, and formulation performance. Parallel biomarker-driven clinical trials are needed to define pharmacokinetic-pharmacodynamic relationships and evaluate disease-modifying potential.},
}

@article {pmid42790258,
year = {2026},
author = {Papandreou, C and Skyfa, VA and Tsilidis, KK and Julvez, J and Sakka, P and Hadjigeorgiou, G and Dardiotis, E and Kosmidis, MH and Yannakoulia, M and Patas, K and Ntanasi, E and Mamalaki, E and Brikou, D and Drouka, A and Chatzipanagiotou, S and Charisis, S and Gu, Y and Scarmeas, N},
title = {Serum metabolite signature of the mediterranean diet adherence and cognitive function: Evidence from two cohorts.},
journal = {Clinical nutrition (Edinburgh, Scotland)},
volume = {66},
number = {},
pages = {106785},
doi = {10.1016/j.clnu.2026.106785},
pmid = {42790258},
issn = {1532-1983},
abstract = {BACKGROUND AND AIMS: The Mediterranean diet (MD) has been consistently associated with favorable cognitive outcomes. However, reliance on self-reported dietary assessment limits accurate characterization of diet-health associations. Circulating metabolites may capture the endogenous metabolic imprint of habitual dietary patterns and provide complementary biological information beyond questionnaire-based measures. We aimed to identify a serum metabolite signature associated with MD adherence and to examine its cross-cohort reproducibility and associations with cognitive performance and trajectories.

METHODS: We analyzed 595 serum metabolites measured by mass spectrometry in 337 adults aged ≥65 years (cognitively normal or with mild cognitive impairment [MCI]) from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). MD adherence was estimated using a validated food-frequency questionnaire (FFQ). A two-stage penalized regression approach was used to derive a metabolite signature of MD adherence. External validation (applying the HELIAD-derived metabolites and coefficients) and recalibration (re-estimating coefficients) were performed in 148 adults aged ≥40 years from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) (cognitively normal or MCI), where MD adherence was assessed using four repeated 24-h dietary recalls. Associations with cognitive performance (global and five domain-specific scores) were examined cross-sectionally and prospectively (median follow-up: 2.8 years in HELIAD; 1.2 years in ALBION).

RESULTS: A 23-metabolite signature enriched in lysophospholipids, plasmalogen and ether-linked phospholipids, long-chain polyunsaturated phosphatidylcholines, and steroid hormone sulfates explained 28.7% of the variance in the MedDietScore in HELIAD (r = 0.54). Direct cross-cohort transferability was limited in ALBION (R[2] = 0.02), but predictive performance improved following cohort-specific recalibration (R[2] = 0.21). The metabolite signature was positively associated with memory performance cross-sectionally and with subsequent language change in HELIAD. Calibration analyses suggested attenuation of FFQ-based associations, with larger effect estimates after correction but wider confidence intervals.

CONCLUSION: A reproducible serum metabolite signature reflects diet-related metabolic variation associated with MD adherence and is linked to cognitive performance in older adults. Rather than functioning as a direct biomarker of adherence, this profile captures the endogenous metabolic imprint of habitual dietary patterns and may complement self-reported dietary measures in nutritional epidemiology.},
}

@article {pmid42790402,
year = {2026},
author = {Reis, C and Hainke, L and Headley, G and Navarro, S and Zanto, TP and Certain, R},
title = {Feasibility of immersive 40 Hz gamma sensory stimulation in early-stage Alzheimer's disease.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {10},
pages = {100679},
doi = {10.1016/j.tjpad.2026.100679},
pmid = {42790402},
issn = {2426-0266},
abstract = {Alzheimer's disease (AD) remains in need of effective therapeutic strategies that are safe, scalable, and broadly accessible. Gamma sensory stimulation (GSS) is a non-invasive neuromodulation approach under investigation as a potential intervention for AD, supported by a favorable safety profile and emerging evidence of biological and clinical effects. This study evaluates the feasibility of delivering immersive GSS through virtual reality (VR) in individuals with early-stage AD. In this single-session, within-subject, sham-controlled early feasibility study, 11 participants with mild cognitive impairment due to AD or mild AD underwent immersive audiovisual stimulation delivered via VR while electroencephalography (EEG) was recorded. Participants engaged in three VR environments of increasing visual and cognitive complexity, in which audiovisual content was modulated at 40 Hz; two environments also included a sham condition. Primary outcomes were safety, tolerability, and 40 Hz neural responses. Secondary analyses compared neural responses and recall and recognition of encoded video-word pairs between 40 Hz and sham stimulation. All participants completed the session without serious adverse events or discontinuations. Stimulation-emergent symptoms were predominantly absent or mild. 40 Hz GSS elicited significantly stronger EEG responses at the stimulation frequency than both baseline and sham stimulation (p < 0.001), confirming target engagement. In exploratory analyses, items encoded during 40 Hz stimulation were better recalled and recognized than those encoded during sham stimulation (all FDR-adjusted p < 0.05). In this single-session study, immersive GSS was well tolerated and elicited frequency-specific 40 Hz EEG responses in individuals with early-stage AD, with no serious safety concerns identified, supporting the feasibility of this delivery approach. The encouraging acute neural and task-specific behavioral differences between 40 Hz and sham stimulation are hypothesis-generating and motivate controlled pilot studies evaluating the effects of repeated use on validated cognitive and functional outcomes.},
}

@article {pmid42790482,
year = {2025},
author = {Ishola, IO and Abdulwahab, KO and Olubodun-Obadun, TG and Oluwatimilehin, IE and Agbaje, TI and Agbaje, OE},
title = {Hesperidin nanoparticles prevent scopolamine-induced cognition impairment through amplification of antioxidant defense system and cholinergic neurotransmission in mice.},
journal = {Nigerian journal of physiological sciences : official publication of the Physiological Society of Nigeria},
volume = {40},
number = {1},
pages = {119-126},
doi = {10.54548/njps.v40i1.14},
pmid = {42790482},
issn = {0794-859X},
mesh = {Animals ; *Scopolamine/toxicity ; *Hesperidin/pharmacology/administration & dosage ; *Antioxidants/pharmacology/metabolism ; Male ; Mice ; *Nanoparticles/administration & dosage ; *Synaptic Transmission/drug effects ; Oxidative Stress/drug effects ; Maze Learning/drug effects ; *Cognitive Dysfunction/chemically induced/prevention & control/metabolism ; Cognition/drug effects ; Cognitive Enhancement ; Acetylcholinesterase/metabolism ; Memory/drug effects ; },
abstract = {The rapid increase in aging population and age-linked cognitive impairment as well as dementia of Alzheimer's type are becoming more prevalent globally. Genetic and environment interactions played key role in dementia pathology. Oxidative stress and cholinergic disruptions are well linked with dementia. Hence, phytochemicals with neuroprotective and antioxidant properties could help ameliorate mitochondrial dysfunction and toxic effects misfolded amyloid-beta and tau proteins in dementia of Alzheimer's type. Previous studies have alluded to the beneficial action of hesperidin in mild cognitive impairment but delivery could be better enhanced in nanoparticulate form. Hence, this study sought to investigate the memory enhancing ability of hesperidin nanoparticles (HES_) on scopolamine-induced memory impairment in mice. Mice were randomly assigned into 6 groups (n=6) and treated as follows; vehicle only, vehicle + SCOP (1mg/kg, i.p.), HES (1,10 and 50mg/kg, p.o., respectively) + SCOP and donepezil (1mg/kg; p.o.) + SCOP for 14 consecutive days followed by behavioral assessment for memory function using open field test, Y-maze, novel object recognition and Morris water maze for locomotion, working, cognition and spatial learning, respectively. The animals were euthanized and brain samples were collected for biochemical assays (oxidative stress markers and acetylcholinesterase activity). SCOP or HES administration did not affect locomotor activity, however, SCOP reduced the percentage alternation behaviour in the Y-maze and discrimination index in NOR tests with no significant change in escape latency time in MWM task indicative of working memory, cognition and spatial learning impairment. In contrast, the pre-administration of HES produced a dose-dependent and significant increase in working memory, cognition and spatial learning abilities. Similarly, HES_ pretreatment reduced scopolamine-induced increase in lipid peroxidation and acetylcholinesterase activity and deficit in antioxidant enzyme activity in the hippocampus and prefrontal cortex caused by SCOP. The results of the present study further showed the potential of hesperidin in nanoparticle form in the enhancement of memory formation through the amplification of antioxidant defense and cholinergic neurotransmission.},
}

Animals
*Scopolamine/toxicity
*Hesperidin/pharmacology/administration & dosage
*Antioxidants/pharmacology/metabolism
Male
Mice
*Nanoparticles/administration & dosage
*Synaptic Transmission/drug effects
Oxidative Stress/drug effects
Maze Learning/drug effects
*Cognitive Dysfunction/chemically induced/prevention & control/metabolism
Cognition/drug effects
Cognitive Enhancement
Acetylcholinesterase/metabolism
Memory/drug effects

@article {pmid42790531,
year = {2026},
author = {Rana, E and Maurya, S},
title = {Letter on: "Assessment of heart rate variability and occurrence of falls in Alzheimer's disease: an exploratory study".},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {8},
pages = {1-2},
doi = {10.1055/s-0046-1827045},
pmid = {42790531},
issn = {1678-4227},
}

@article {pmid42790532,
year = {2026},
author = {Rodrigues, EA and Danaga, AR and Carvalho, EFT and Filho, CAS and Ponce, JB and Jacinto, AF},
title = {Reply to: "Assessment of heart rate variability and occurrence of falls in Alzheimer's disease: an exploratory study".},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {8},
pages = {1-2},
doi = {10.1055/s-0046-1829033},
pmid = {42790532},
issn = {1678-4227},
}

@article {pmid42790614,
year = {2026},
author = {Sun, C and Sha, S and Kang, J and Gao, X and Cheng, X and Huo, X and Hang, Z and Zhou, L and Li, Y and Xing, C and Luo, E and Du, H},
title = {Targeting neuronal injury with intranasal Arc-engineered exosomes rescues cognitive deficits in Alzheimer's disease via the mTOR-autophagy pathway.},
journal = {Nanomedicine : nanotechnology, biology, and medicine},
volume = {},
number = {},
pages = {103028},
doi = {10.1016/j.nano.2026.103028},
pmid = {42790614},
issn = {1549-9642},
abstract = {The pathological complexity of Alzheimer's disease (AD) necessitates multifaceted therapeutic strategies. By integrating single-nucleus RNA sequencing analysis of 143,214 nuclei, this study identified excitatory neurons as the pivotal locus of cellular damage, manifesting significant dysregulation of pathways associated with proteostasis and autophagy. To counteract these cellular deficits, we developed a neuron-centric targeting strategy utilizing neural stem cell-derived exosomes engineered to overexpress the scaffolding protein Arc (Arc-exo). Following intranasal administration, Arc-exo demonstrated efficient central nervous system accumulation and achieved precision delivery by leveraging the intrinsic neurorestorative properties of the Arc protein and its specific affinity for neurons. Experimental results demonstrated that Arc-exo significantly alleviated AD pathological symptoms by reducing β-amyloid deposition, suppressing neuroinflammation, and repairing neuronal damage. Further mechanistic investigation revealed that Arc-exo restored cellular homeostasis by inhibiting the mTOR signaling pathway and reactivating autophagy. This study highlights engineered exosomes as efficient nanoplatforms for precision therapy in neurodegenerative diseases.},
}

@article {pmid42790732,
year = {2026},
author = {Lahouel, A and Harrouche, K and Oguz, E and Türkan, F and Cetin, A and Khelili, S},
title = {A synthetic Benzothiazole-Thiourea Derivative with Multi-Target Potential Activity for Alzheimer's Disease: Antioxidant Properties and Mechanistic Insights.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {111199},
doi = {10.1016/j.neuropharm.2026.111199},
pmid = {42790732},
issn = {1873-7064},
abstract = {H74 is a benzothiazole derivative bearing a thiourea moiety molecule that was synthesized in our laboratory. The antioxidant activity and the potential effects of H74 on multiple targets associated with Alzheimer's disease (AD) were investigated. The anticholinesterase and the antioxidant activities of H74 were tested in vitro. The antioxidant activity of H74 was further evaluated in vivo in aged NMRI mice. The cytotoxicity of H74 was evaluated in Uppsala 87 Malignant Glioma (U87-MG) cells using the MTT assay. Whereas, the drug-likeness and potential multitarget activity of H74 against AD were analyzed using in silico approaches. H74 was potent in inhibiting Acetylcholinesterase (AChE) activity and reducing ABTS and DPPH radicals and scavenging H2O2. H74 inhibited as well lipid peroxidation in rat liver homogenate and the autoxidation of reduced glutathione (GSH) in alkaline medium. The administration of H74 to aged NMRI mice for three days (50 mg/kg/day, i.p.) induced antioxidant effect in the brain reflected by a significant decrease in MDA levels and an increase in GSH levels, although the increase in GSH was not statistically significant. However, H74 showed cytotoxicity by reducing the viability of U87 MG cells. ADME analysis revealed that H74 fits in the drug-likeness rules. SwissTargetPrediction suggested that H74 might interact with several major targets of AD, namely, Cyclin dependent kinase 5, (CDK5), Glycogen synthase kinase 3 beta (GSK3β), beta-Secretase 1(BACE1), AChE. Molecular docking results further suggested that H74 might act as a potential inhibitor to these enzymes. Molecular dynamics (MD) simulations supported the structural stability of the simulated protein-H74 complexes throughout the 200 ns simulation period. Further studies are required to experimentally validate the multitarget effects of H74 on AD-related targets and to evaluate its efficacy in experimental models of AD.},
}

@article {pmid42790767,
year = {2026},
author = {Bi, H and Sun, M and Ma, Q and Li, X and Wang, Y},
title = {RNA m6A demethylase FTO in central nervous system disorders: Mechanisms and therapeutic implications.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {},
number = {},
pages = {111942},
doi = {10.1016/j.pnpbp.2026.111942},
pmid = {42790767},
issn = {1878-4216},
abstract = {The fat mass and obesity-associated protein (FTO) is an obesity-related protein that is widely expressed in different tissues throughout the human body, with relatively high expression levels observed in the brain. Initial investigations into FTO mainly concentrated on its involvement in the development of obesity and diabetes. However, accumulating evidence has subsequently identified FTO as an N6-methyladenosine (m6A) demethylase, suggesting that it may participate in various neurological processes, including neural differentiation, synaptic plasticity, and neuroinflammation, through modulation of RNA m6A methylation. Increasing studies have demonstrated that FTO is involved in the pathophysiological mechanisms and therapeutic responses of a range of central nervous system (CNS) disorders, including Parkinson's disease, epilepsy, Alzheimer's disease, stroke, brain tumors, depression, autism, and substance use disorders. This review summarizes the potential roles of FTO in the pathogenesis and treatment of CNS disorders, with the aim of providing novel perspectives and potential therapeutic targets for further research and clinical intervention in CNS diseases.},
}

@article {pmid42790799,
year = {2026},
author = {Abinawanto, and Sophian, A},
title = {Intrinsically disordered proteins and liquid-liquid phase separation: Molecular grammar, condensate physiology, and disease-relevant phase transitions.},
journal = {Biochimica et biophysica acta. Proteins and proteomics},
volume = {},
number = {},
pages = {141183},
doi = {10.1016/j.bbapap.2026.141183},
pmid = {42790799},
issn = {1878-1454},
abstract = {Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) of proteins constitute a substantial and functionally critical fraction of the eukaryotic proteome. Through multivalent, low-affinity interactions encoded in their low-complexity domains (LCDs), IDPs drive liquid-liquid phase separation (LLPS)-a physicochemical process that produces membraneless biomolecular condensates serving as dynamic reaction hubs within cells. Recent advances have substantially refined the conceptual framework governing condensate biophysics: the phase separation coupled to percolation (PSCP) model now recognizes that condensates are viscoelastic network fluids arising from the synergy between density transitions and connectivity (percolation) transitions, rather than simple LLPS alone. This updated mechanistic understanding, combined with proteome-wide computational tools and AI-driven prediction models, is rapidly transforming the field. Physiologically, condensates regulate transcription at super-enhancers, modulate RNA metabolism in stress granules, and orchestrate ribosome biogenesis in the nucleolus. Pathologically, aberrant liquid-to-solid transitions of disease-associated IDPs-including TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia, tau in Alzheimer's disease, and α-synuclein in Parkinson's disease-represent a convergent pathomechanism across neurodegenerative proteinopathies. Post-translational modifications, particularly phosphorylation, arginine methylation, and ubiquitination, function as a dynamic regulatory code controlling condensate assembly and dissolution. The emerging paradigm of condensate-modifying therapeutics (c-mods) identifies biomolecular condensates as druggable entities and proposes four mechanistic strategies-dissolvers, inducers, localizers, and morphers-to restore normal phase behavior in disease. This review integrates the most current molecular, cellular, and biomedical insights into IDP-driven phase separation, highlighting open questions and translational opportunities.},
}

@article {pmid42790827,
year = {2026},
author = {Dong, YR and Wang, JR and Yang, Y and Cao, SP and Zhou, MC and Zeng, SX and Mi, HQ and Wang, JH and Zang, CX and Li, FF and Bao, XQ and Zhang, D},
title = {Src inhibition attenuates neuroinflammation via promoting p62 UFMylation-dependent microglial mitophagy.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {118503},
doi = {10.1016/j.bcp.2026.118503},
pmid = {42790827},
issn = {1873-2968},
abstract = {Src tyrosine kinase, a prototypical oncogene, has recently emerged as a critical modulator of neuroinflammation. However, the precise molecular mechanisms underlying its regulatory role remain poorly characterized. Herein, pharmacological inhibition of Src attenuated lipopolysaccharide-induced neuroinflammatory responses in both in vivo and in vitro experiments. Proteomic analysis identified that microglial mitophagy and p62 UFMylation were involved in Src-mediated neuroinflammation. Further studies demonstrated that Src inhibition reduced the phosphorylation of UFL1, the E3 ligase of UFM1 conjugation, which correlated with decreased UFMylation of p62. Notably, the function of p62 was regulated by a dynamic interplay between UFMylation and ubiquitination. Consequently, diminished p62 UFMylation competitively facilitated ubiquitination of p62 at the same residue. This led to p62 degradation and induced microglial mitophagy, ultimately alleviating neuroinflammation. Moreover, Src inhibition significantly ameliorated neuroinflammatory pathology and cognitive deficits in LPS-challenged mice, an effect attributed to p62 UFMylation-mediated microglial mitophagy. Collectively, our findings revealed that the Src-UFL1-p62 signaling axis governing microglial mitophagy and neuroimmune homeostasis, positioning Src kinase as a promising therapeutic target for Alzheimer's disease and related neuroinflammatory disorders.},
}

@article {pmid42790907,
year = {2026},
author = {Fu, J and Li, F and Chen, S and Yang, J and Huang, J and Pang, D and Wei, Q and Li, C and Song, W and Ou, R and Zhao, B and Chen, X and Shang, H},
title = {Trends, patterns and outcomes in hospitalisations for Alzheimer's disease: a 14-year retrospective analysis in Southwest China (2011-2024).},
journal = {BMJ open},
volume = {16},
number = {9},
pages = {e114860},
doi = {10.1136/bmjopen-2025-114860},
pmid = {42790907},
issn = {2044-6055},
mesh = {Humans ; Female ; *Alzheimer Disease/therapy/epidemiology/economics/mortality ; Retrospective Studies ; China/epidemiology ; *Hospitalization/trends/economics/statistics & numerical data ; Aged ; Male ; Length of Stay/trends/statistics & numerical data ; Hospital Mortality/trends ; Risk Factors ; Comorbidity ; Aged, 80 and over ; Patient Readmission/statistics & numerical data/trends ; Health Care Costs ; },
abstract = {OBJECTIVES: To analyse temporal trends, clinical outcomes and healthcare costs of Alzheimer's disease (AD)-related hospitalisations in Southwest China over 14 years and identify modifiable risk factors for adverse outcomes.

DESIGN: Retrospective time-series analysis of electronic health records.

SETTING: A tertiary referral centre in Southwest China (covering Sichuan, Guizhou, Yunnan and Xinjiang provinces); single-centre study.

PARTICIPANTS: 4970 hospitalisations of patients with a confirmed diagnosis of AD (ICD-10: G30) discharged between January 2011 and December 2024, with a mean age of 77.8±0.14 years, and 51.7% were female.

INTERVENTIONS: Not applicable (observational study).

Primary outcomes were poor hospital outcomes, defined as prolonged length of stay (>14 days), frequent readmissions (≥4 admissions over the study period) and in-hospital mortality. Secondary outcomes included annual trends in hospitalisation rates, total costs and prevalence of comorbidities.

RESULTS: Comorbidities (64.75% of admissions, mainly infections and fractures) and admission to non-neurology departments independently increased risks of prolonged stay (OR=5.248, 95% CI 4.287 to 6.425; p<0.001), frequent readmissions (OR=1.735, 95% CI 1.236 to 2.435; p=0.001) and in-hospital mortality (OR=2.176, 95% CI 1.506 to 3.146; p<0.001). Hospitalisations rose annually by 7.65% (95% CI 3.00% to 12.31%; p=0.001) and total costs by 8.32% (p<0.001), yet the composite poor-outcome rate declined from 70% to 50% after 2018 (annual percent change, -6.32%, p=0.004), coinciding with fewer comorbidity-driven admissions and increased neurology department care.

CONCLUSIONS: Comorbidities and non-neurology admissions were associated with increased risks of adverse outcomes in this cohort. The post-2018 temporal improvements coincided with a decline in comorbidity-driven admissions and increased neurology department use. Further prospective studies are needed to confirm these associations.

TRIAL REGISTRATION: Not applicable (observational study; not registered).},
}

Humans
Female
*Alzheimer Disease/therapy/epidemiology/economics/mortality
Retrospective Studies
China/epidemiology
*Hospitalization/trends/economics/statistics & numerical data
Aged
Male
Length of Stay/trends/statistics & numerical data
Hospital Mortality/trends
Risk Factors
Comorbidity
Aged, 80 and over
Patient Readmission/statistics & numerical data/trends
Health Care Costs

@article {pmid42791416,
year = {2026},
author = {Kawakami, N and Hasegawa, T and Kakinuma, K and Iseki, C and Kanno, S},
title = {Painless legs and moving toes phenotype in corticobasal syndrome with biomarker evidence of Alzheimer's disease: a case report.},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
volume = {47},
number = {10},
pages = {},
pmid = {42791416},
issn = {1590-3478},
support = {24K14371//Japan Society for the Promotion of Science/ ; },
}

@article {pmid42791463,
year = {2026},
author = {Li, Z and Liu, Z and Zhang, Y and Lei, Y and Wang, Y},
title = {Brain-Wide Multi-Trait Genetic Integration Implicates Lysosomal and Metabolic Axes Linking Visual Disturbance and Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {42791463},
issn = {1559-1182},
mesh = {*Alzheimer Disease/genetics/metabolism/complications ; Humans ; *Brain/metabolism/pathology ; Genome-Wide Association Study ; *Lysosomes/metabolism/genetics ; *Vision Disorders/genetics/metabolism/complications ; *Genetic Predisposition to Disease ; *Quantitative Trait, Heritable ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; },
abstract = {Visual impairment has been proposed as a potentially modifiable risk factor for dementia, including Alzheimer's disease (AD), but the biological mechanisms linking visual disturbance to AD remain unclear. It is unknown whether AD and visual disturbance share specific genetic determinants, how such effects are distributed across brain regions, and whether they converge on discrete molecular pathways that could be targeted for prevention or treatment. Multi-trait analysis of GWAS was applied to summary statistics from large-scale GWAS of AD and a visual disturbance (VD) phenotype, yielding VD-informed AD association statistics (VDAD). Gene-level associations were then mapped across brain tissues by integrating single-tissue and cross-tissue transcriptome-wide association studies, brain proteome-wide association analyses and gene-based tests. A small set of genes (GRN, PVR and RAB29) emerged as consistently associated with both AD and VDAD. A broader panel of genes showed partially overlapping but also phenotype-specific architectures, with PM20D1 and LRRC37A2 more prominent in AD and SLC41A1 and MTCH2 more strongly implicated in VDAD. These signals were anchored to frontal cortical, hippocampal, cerebellar and striatal tissues, suggesting involvement of circuits that integrate visual input with memory, motor control and balance. Network and pathway analyses highlighted a GRN-centered lysosomal axis and metabolic pathways linked to PM20D1 and SLC41A1 as candidate mechanisms bridging visual disturbance and AD risk. These findings support the view that visual disturbance-related AD risk is shaped by a limited set of genes and pathways that are supported across complementary molecular analyses and mapped to distributed brain/CNS reference tissues. These findings generate testable hypotheses for future studies with detailed visual phenotyping.},
}

*Alzheimer Disease/genetics/metabolism/complications
Humans
*Brain/metabolism/pathology
Genome-Wide Association Study
*Lysosomes/metabolism/genetics
*Vision Disorders/genetics/metabolism/complications
*Genetic Predisposition to Disease
*Quantitative Trait, Heritable
Phenotype
Polymorphism, Single Nucleotide/genetics

@article {pmid42791497,
year = {2026},
author = {Nevyhoštěná, M and Komersová, A and Svoboda, R and Pejchal, V and Pospíšilová, A and Muselík, J and Łapa, A and Koczurkiewicz-Adamczyk, P},
title = {Personalized 3D-Printed Affinisol-Based Pharmaceutical Delivery Systems: The Case Study for Alternative Sulfonamides for Alzheimer's Disease.},
journal = {Macromolecular bioscience},
volume = {26},
number = {9},
pages = {e70266},
doi = {10.1002/mabi.70266},
pmid = {42791497},
issn = {1616-5195},
support = {SGS_2026_006//Internal Grant Agency of the University of Pardubice/ ; },
mesh = {*Printing, Three-Dimensional ; *Alzheimer Disease/drug therapy/pathology ; Humans ; *Sulfonamides/chemistry/pharmacology/therapeutic use/pharmacokinetics ; Tablets ; Solubility ; *Precision Medicine ; *Drug Delivery Systems ; Drug Liberation ; },
abstract = {The use of hot melt extrusion combined with fused deposition modeling 3D printing was explored to enhance the solubility and bioavailability of poorly water-soluble compounds intended for Alzheimer's disease (AD) therapy. AD, a neurodegenerative disorder with no definitive treatment, affects millions worldwide, underscoring the urgent need for effective and personalized therapeutic strategies. Four sulfonamide-derived compounds, identified as potential AD therapeutics, were synthesized and successfully incorporated (loads between 10 and 50 wt.%) into customized, 3D-printed oral dosage forms. These 3D-printed tablets were evaluated for properties such as hardness, thermo-analytical characterization, dissolution, cytotoxicity, and stability. Notably, successful amorphization of the incorporated APIs was observed in most 3D-printed tablets, which may be critical for improving solubility. In vitro dissolution testing revealed multiple favorable release profiles, with several formulations demonstrating sustained or enhanced drug release suitable for the therapeutic requirements of AD. When compared to the dissolution data of the corresponding conventional matrix tablets, the present 3D-printed tablets offered superior or comparable dissolution characteristics, demonstrating the potential of personalized medicine and remote digital control for optimizing patient-specific treatments.},
}

*Printing, Three-Dimensional
*Alzheimer Disease/drug therapy/pathology
Humans
*Sulfonamides/chemistry/pharmacology/therapeutic use/pharmacokinetics
Tablets
Solubility
*Precision Medicine
*Drug Delivery Systems
Drug Liberation

@article {pmid42791509,
year = {2026},
author = {El-Feky, AM and Ibrahim, NE and Aboulthana, WM},
title = {Harvest-Time-Dependent variations in phytochemistry and in vitro bioactivities of Vitis vinifera Leaves.},
journal = {BMC complementary medicine and therapies},
volume = {26},
number = {1},
pages = {},
pmid = {42791509},
issn = {2662-7671},
mesh = {*Vitis/chemistry ; *Plant Leaves/chemistry ; *Plant Extracts/pharmacology/chemistry ; Antioxidants/pharmacology/chemistry ; *Phytochemicals/pharmacology/chemistry ; Chromatography, High Pressure Liquid ; Animals ; Flavonoids/analysis ; Anti-Inflammatory Agents/pharmacology ; },
abstract = {BACKGROUND: Vitis vinifera L. leaves are rich in bioactive phytochemicals, but their composition and biological activities may vary considerably with harvest time. This study investigated harvest-dependent changes in the phytochemical profile and in vitro biological activities of grape leaves.

METHODS: Methanolic extracts of V. vinifera leaves collected in March, May, and September were evaluated for photosynthetic pigments, total polyphenols, flavonoids, and tannins. HPLC analysis was used to characterize individual phenolic and flavonoid constituents, while major compounds were isolated and structurally identified. The extracts were further assessed for antioxidant and radical-scavenging, antidiabetic, anti-Alzheimer's, anti-inflammatory, anti-arthritic, and cytotoxic activities.

RESULTS: Harvest time markedly affected the phytochemical composition and biological activities of the leaves. The May-harvested leaves showed the highest levels of total chlorophyll, polyphenols, flavonoids, and tannins, whereas carotenoids were comparatively higher in the September and March samples. HPLC analysis revealed greater accumulation of phenolic and flavonoid constituents in the May extract, with chlorogenic acid, rosmarinic acid, gallic acid, and naringenin among the predominant compounds. Consistently, the May extract exhibited the strongest antioxidant and radical-scavenging activities and showed superior inhibitory effects in the antidiabetic, anti-Alzheimer's, anti-inflammatory, anti-arthritic, and cytotoxic assays compared with the other harvest periods.

CONCLUSION: Harvest time substantially influences the accumulation of bioactive constituents and the in vitro biological potential of V. vinifera leaves. Among the investigated periods, May appeared to be the most favorable harvest time for obtaining grape leaves enriched in bioactive phytochemicals with promising biological activities, supporting their potential valorization as a value-added viticultural by-product.},
}

*Vitis/chemistry
*Plant Leaves/chemistry
*Plant Extracts/pharmacology/chemistry
Antioxidants/pharmacology/chemistry
*Phytochemicals/pharmacology/chemistry
Chromatography, High Pressure Liquid
Animals
Flavonoids/analysis
Anti-Inflammatory Agents/pharmacology

@article {pmid42791531,
year = {2026},
author = {Goldhardt, O and Robles, CM and Eberl, M and Dreyer, T and Soosaipillai, A and Diamandis, EP and Priller, J and Hoffmann, D and Wettengel, JM and Bustamante, HA and Salazar, P and Thaler, M and Otth, C and Slater, IPE and Grimmer, T},
title = {Herpes simplex virus and kallikrein-related peptidases - a functional connection in Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {42791531},
issn = {1758-9193},
mesh = {Humans ; *Alzheimer Disease/cerebrospinal fluid/virology/enzymology ; *Kallikreins/cerebrospinal fluid/genetics/metabolism ; tau Proteins/cerebrospinal fluid ; Amyloid beta-Peptides/cerebrospinal fluid ; Female ; Male ; Aged ; Biomarkers/cerebrospinal fluid ; *Herpesvirus 1, Human/immunology ; Aged, 80 and over ; Peptide Fragments/cerebrospinal fluid ; *Herpes Simplex/cerebrospinal fluid ; Animals ; RNA, Small Interfering/metabolism ; },
abstract = {BACKGROUND: The viral hypothesis of Alzheimer's disease (AD) proposes that neurotropic pathogens may interact with amyloid and tau pathology, but the evidence remains controversial. We investigated whether cerebrospinal fluid (CSF) kallikrein-related peptidase 6 (KLK6) is associated with AD biomarkers and with an intrathecal anti-HSV immune response in patients with AD, and whether HSV-1 infection alters KLK6 expression in cell culture models.

METHODS: CSF KLKs and AD biomarkers were analyzed in patients with AD. HSV-1 serostatus and anti-HSV-1/2 CSF-to-serum antibody index (HSV-AI) were used as markers of previous or ongoing intrathecal anti-HSV immune response. In vitro, HSV-1 infection and KLK6 knockdown were examined in human cell models.

RESULTS: CSF-KLK6 correlated with tau and amyloid biomarkers. In HSV-1-seropositive patients, HSV-AI was associated with CSF-KLK6, although the effect size was modest and the association was strongly context-dependent on the Aβ42/40 ratio. In vitro, productive HSV-1 infection induced and stabilized KLK6 protein expression, and KLK6 knockdown reduced HSV-1 protein expression and infectious progeny in HaCaT cells.

CONCLUSIONS: KLK6 is associated with AD biomarkers and with an intrathecal anti-HSV immune response in a subset of patients with AD. The in vitro data support a functional relationship between HSV-1 infection and KLK6, but the clinical findings are associative and do not demonstrate ongoing CNS HSV-1 replication or causality. These findings warrant independent validation. However, this research provides further evidence for a role of HSV-1 in the pathophysiology of AD.},
}

Humans
*Alzheimer Disease/cerebrospinal fluid/virology/enzymology
*Kallikreins/cerebrospinal fluid/genetics/metabolism
tau Proteins/cerebrospinal fluid
Amyloid beta-Peptides/cerebrospinal fluid
Female
Male
Aged
Biomarkers/cerebrospinal fluid
*Herpesvirus 1, Human/immunology
Aged, 80 and over
Peptide Fragments/cerebrospinal fluid
*Herpes Simplex/cerebrospinal fluid
Animals
RNA, Small Interfering/metabolism

@article {pmid42791560,
year = {2026},
author = {Gnörich, J and Kusche-Palenga, J and Kling, A and Dehsarvi, A and Bronte, A and Frontzkowski, L and Zatcepin, A and Zaganjori, M and Schöberl, F and Roemer-Cassiano, SN and Rauchmann, BS and Kurz, C and Palleis, C and Bernhardt, AM and Jäck, A and Katzdobler, S and Scheifele, M and Bauer, T and Bischof, GN and Eimeren, TV and Drzezga, A and Häckert, J and Perneczky, R and Rullmann, M and Buerger, K and Werner, RA and Zwergal, A and Levin, J and Bartenstein, P and Sabri, O and Barthel, H and Stöcklein, S and Höglinger, G and Franzmeier, N and Brendel, M},
title = {Dynamic [[18]F]PI-2620 recording facilitates prediction of β-amyloid positivity and simultaneous staging of tau and neurodegeneration.},
journal = {Molecular neurodegeneration},
volume = {21},
number = {1},
pages = {},
pmid = {42791560},
issn = {1750-1326},
mesh = {Humans ; Positron-Emission Tomography/methods ; *Amyloid beta-Peptides/metabolism ; Female ; *Tauopathies/diagnostic imaging/metabolism ; Male ; Aged ; *tau Proteins/metabolism ; *Alzheimer Disease/diagnostic imaging/metabolism ; Middle Aged ; Brain/metabolism ; Biomarkers ; Magnetic Resonance Imaging ; *Neurodegenerative Diseases/diagnostic imaging/metabolism ; Fluorine Radioisotopes ; Pyridines ; },
abstract = {BACKGROUND: Patients with Alzheimer's disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers and structural MRI, A/T/N assessment incorporates β-amyloid-PET (A), tau-PET (T), and [[18]F]FDG-PET (N). We evaluated if dynamic features of tau-PET with [[18]F]PI-2620 allow prediction of β-amyloid positivity and simultaneous staging of tau and neurodegeneration in individual patients using a single imaging session.

METHODS: We studied 129 patients with tauopathies, comprising 47 patients with β-amyloid-positive 3/4-repeat tauopathy and 82 patients with β-amyloid-negative primary 4-repeat tauopathies, alongside 17 healthy controls. Participants underwent 60-minute dynamic [[18]F]PI-2620 tau-PET. Kinetic modelling simultaneously provided tracer efflux rate (K2a) as a predictor for β-amyloid status, distribution volume ratio (DVR) for regional tau burden, and relative perfusion (R1) as a marker of neurodegeneration. These parameters were validated against β-amyloid-PET, [[18]F]FDG-PET, volumetric MRI, and cerebrospinal fluid biomarkers using receiver operating characteristic and correlation analyses and visual assessments. [[18]F]PI-2620K2a-based prediction of β-amyloid positivtiy was additionally tested in an independent, clinically heterogeneous validation cohort of 97 individuals.

RESULTS: [[18]F]PI-2620K2a differentiated tau isoform compositions despite clinically overlapping presentations and tau-PET patterns, demonstrating reduced cortical tracer clearance in 3/4-repeat compared with 4-repeat tauopathies. [[18]F]PI-2620K2a remained sensitive in individuals with visually negative or low [[18]F]PI-2620DVR signals and outperformed both tau burden and perfusion for predicting β-amyloid status, achieving an area under the curve of 0.99, a positive predictive value of 91.5%, and a negative predictive value of 95.1%. Performance remained robust in the independent validation cohort, with an area under the curve of 0.98, a positive predictive value of 87.9%, and a negative predictive value of 95.3%. [[18]F]PI-2620DVR quantified regional tau patterns, with cortical predominance in 3/4-repeat tauopathy and subcortical involvement in 4-repeat tauopathies. [[18]F]PI-2620R1 exhibited strong quantitative and visual associations with established markers of neurodegeneration. Integration of K2a, DVR, and R1 in disease-specific composite regions enabled individualized three-dimensional A/T/N staging.

CONCLUSIONS: Dynamic [[18]F]PI-2620 PET imaging facilitates assessment of the β-amyloid status and regional staging of tau and neurodegeneration during a single acquisition. This one-stop-shop approach may reduce radiation exposure, streamline diagnostic workflows, and facilitate personalized disease profiling.},
}

Humans
Positron-Emission Tomography/methods
*Amyloid beta-Peptides/metabolism
Female
*Tauopathies/diagnostic imaging/metabolism
Male
Aged
*tau Proteins/metabolism
*Alzheimer Disease/diagnostic imaging/metabolism
Middle Aged
Brain/metabolism
Biomarkers
Magnetic Resonance Imaging
*Neurodegenerative Diseases/diagnostic imaging/metabolism
Fluorine Radioisotopes
Pyridines

@article {pmid42791577,
year = {2026},
author = {Min-Kaung-Wint-Mon, and Kida, H and Kimura, R and Mitsushima, D},
title = {Riluzole shifts glial responses to protect synapses and memory in Aβ oligomer-treated rats.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {42791577},
issn = {1742-2094},
support = {JPMJSP2111//JST SPRING/ ; 23K06348//Ministry of Education, Culture, Sports, Science, and Technology of Japan/ ; YU AI project//Yamaguchi University/ ; },
mesh = {Animals ; *Riluzole/pharmacology/therapeutic use ; Male ; *Amyloid beta-Peptides/toxicity ; *Synapses/drug effects/pathology ; Rats ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Neuroglia/drug effects/metabolism ; *Peptide Fragments/toxicity ; *Memory/drug effects ; *Memory Disorders/chemically induced/drug therapy/pathology ; Rats, Sprague-Dawley ; },
abstract = {BACKGROUND: Soluble Aβ1-42 (amyloid beta) oligomers are potent neurotoxins that disrupt synaptic function, alter glial responses, and lead to memory impairment in Alzheimer's disease (AD). Riluzole, a glutamate modulator approved for amyotrophic lateral sclerosis, reduces neuronal hyperexcitability, yet its in vivo effects on Aβ oligomer-induced cognitive dysfunction and glial alterations remain incompletely understood. Here, we investigated whether riluzole ameliorates Aβ1-42 oligomer-induced memory impairment and associated hippocampal pathology.

METHODS: Aβ1-42 oligomers were bilaterally microinjected into the dorsal CA1 region of freely moving male rats, followed by daily riluzole administration for 7 days. Then, the animals underwent a battery of behavioural tests before being sacrificed for immuno-histochemical studies. Glial engulfment of Aβ and synapse was visualized through multiplex immunohistochemistry combined with super-resolution microscopy and three-dimensional (3D) reconstruction.

RESULTS: Behavioral analyses revealed that riluzole significantly improved hippocampus-dependent memory, including contextual learning and spatial working memory, without affecting locomotor activity, anxiety-like behavior, or pain sensitivity. At the cellular level, riluzole reduced neuronal Aβ accumulation which was strongly associated with improved learning performance across individual animals. It enhanced robust Aβ internalization and lysosomal processing within astrocytes and microglia. Though Aβ-induced glial recruitment and activation persisted, riluzole enhanced morphological remodeling and shifted glial cells towards neuroprotective phenotype. Riluzole also attenuated Aβ-induced neuronal apoptosis, dendritic degeneration, and dendritic spine loss across the dorsal CA1 sublayers, and limited complement-mediated synaptic elimination by microglia.

CONCLUSION: By enhancing glial Aβ clearance and preserving synaptic integrity, riluzole effectively counteracts Aβ-driven cognitive decline. Together, these findings highlight coordinated glial remodeling as a physiologically relevant mechanism at a therapeutically actionable stage of AD.},
}

Animals
*Riluzole/pharmacology/therapeutic use
Male
*Amyloid beta-Peptides/toxicity
*Synapses/drug effects/pathology
Rats
*Neuroprotective Agents/pharmacology/therapeutic use
*Neuroglia/drug effects/metabolism
*Peptide Fragments/toxicity
*Memory/drug effects
*Memory Disorders/chemically induced/drug therapy/pathology
Rats, Sprague-Dawley

@article {pmid42791883,
year = {2026},
author = {Alshamlan, H},
title = {DiAbot: A Conversational AI System Coupling Large Language Models with an Interpretable Decision Tree for CDR-Style Dementia Screening.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/bioengineering13091013},
pmid = {42791883},
issn = {2306-5354},
abstract = {Alzheimer's disease and related dementias are projected to affect more than 150 million people worldwide by 2050. Early staging with validated instruments such as the Clinical Dementia Rating (CDR) scale is essential for timely intervention, yet access to clinician-administered CDR assessment remains constrained by workforce, time, and geographic barriers. This study complements a previously published machine learning pipeline for Alzheimer's disease prediction by addressing the downstream task of dementia staging. Because the global CDR score is already derived from the six sub-domain ratings through an established rule-based procedure, the contribution reported here lies not in discovering that mapping but in encoding it in a transparent, deployable form: an explainable decision tree classifier embedded in DiAbot, a large-language-model-fronted conversational system that supports self-administered CDR-style assessment. We extracted 13,453 CDR records from the Alzheimer's Disease Neuroimaging Initiative (ADNI), removed administrative variables, invalid entries, and missing rows (final n = 13,290), and trained decision tree classifiers under two impurity criteria, Information Gain and Gini Index, using a 70/30 stratified record-level hold-out and ten-fold stratified record-level cross-validation. This classifier-level evaluation uses the six domain scores as recorded during ADNI's clinician-administered assessment, not scores elicited by the DiAbot chatbot; the trained classifier was separately embedded in a web application in which a prompt-engineered large language model conducts a CDR-style interview and normalizes responses to ordinal domain scores, but the end-to-end accuracy of that full conversational pipeline (chatbot elicitation through to final CDGLOBAL) has not yet been measured, and is not what the headline accuracy figures below report. The Information Gain Decision Tree reproduced the established mapping from the six CDR sub-domain scores to the CDGLOBAL with 99.86% accuracy under the record-level hold-out protocol (matching macro-averaged precision, recall, and F1-score), with a ten-fold record-level cross-validated mean of 99.81% (SD 0.07); this result represents fidelity to the established CDR scoring rule rather than independent dementia-diagnosis accuracy. Gini-based trees performed almost identically (99.79% hold-out, 99.74% cross-validated). Memory dominated feature importance, consistent with its role as the primary domain in the official CDR scoring algorithm. Residual misclassifications were confined to adjacent CDR stages. Because the CDGLOBAL is deterministically derived from the six sub-domain scores, these figures should be read throughout as evidence of high-fidelity reconstruction of the established CDR scoring relationship, not as general dementia-diagnosis accuracy comparable to imaging- or biomarker-based classifiers; further, participant-independent generalization remains unverified under the record-level protocol evaluated here. An interpretable classifier embedded in a conversational front-end can nonetheless make standardized CDR-style staging more widely accessible while preserving clinical inspectability; the resulting system is positioned as a screening-stage adjunct to, and not a replacement for, clinician-administered CDR assessment.},
}

@article {pmid42791913,
year = {2026},
author = {Ghesquiere, M and Christinaki, E and Lemmens, S and Van Eijgen, J and Beeckmans, L and Ghinis, A and Jacobs, T and Keer, KV and Wehbi, Z and De Groef, L and Dahdouh-Guebas, Y and Charle, W and Vande Casteele, T and Vandenbulcke, M and Vanderlinden, G and Laere, KV and Schaeverbeke, J and Vandenberghe, R and Ceccarini, J and De Vos, M and Stalmans, I},
title = {Multimodal Retinal Imaging for the Detection of Early Alzheimer's Disease: Combining Biochemical, Structural, and Vascular Biomarkers.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {13},
number = {9},
pages = {},
doi = {10.3390/bioengineering13091041},
pmid = {42791913},
issn = {2306-5354},
support = {12ZZM23N//Research Foundation - Flanders/ ; 1SHC824N//Research Foundation - Flanders/ ; 2020/0032, 2021/0036//Internationale Stichting Alzheimer Onderzoek/ ; FWO-ERANET S007721N//Research Foundation - Flanders/ ; G0C0319N//Research Foundation - Flanders/ ; C24/18/095//KU Leuven/ ; Sequoia Fund for Research on Ageing and Mental Health//KU Leuven/ ; 1292326N//Research Foundation - Flanders/ ; 12Y1623N//Research Foundation - Flanders/ ; G093218N//Research Foundation - Flanders/ ; C24-17-063//KU Leuven/ ; },
abstract = {Alzheimer's disease (AD) pathology is increasingly recognized to manifest in the retina, offering a non-invasive window for early biomarker discovery. This proof-of-concept study investigated whether multimodal retinal imaging-hyperspectral imaging (HSI), optical coherence tomography (OCT), and color fundus photography (CFP)-can differentiate individuals with and without cerebral amyloid-beta (Aβ) pathology in 40 participants with PET-confirmed Aβ status (17 Aβ+, cognitively normal or with mild cognitive impairment; 23 Aβ- cognitively normal controls). HSI-derived gray-level co-occurrence matrix (GLCM) texture, OCT-derived ganglion cell-inner plexiform layer (GC-IPL) thickness, and CFP-derived vascular biomarkers (VBMs) were extracted, and logistic regression with leave-one-out cross-validation assessed classification performance per modality, alone and combined; the cohort was supplemented with AD dementia patients for an exploratory cross-sectional comparison across disease-stage groups. HSI showed nominally lower GLCM correlation at 466 nm in Aβ+ participants, most pronounced in the inferior macula (AUC = 0.72). GC-IPL thickness showed a similar inferior-predominant regional pattern. Combining HSI and GC-IPL features yielded the best performance (AUC = 0.84; sensitivity = 0.82; specificity = 0.78), although this improvement over the unimodal models did not reach statistical significance, whereas vascular biomarkers contributed minimally. In an exploratory cross-sectional comparison across AD stage groups drawn from two cohorts, HSI features showed a non-monotonic pattern, decreasing in early Aβ+ stages and rising again in dementia. These findings provide preliminary evidence of complementary information between HSI and OCT for detecting retinal biomarkers of early-stage AD, supporting multimodal retinal imaging as a scalable screening approach warranting validation in larger, longitudinal cohorts.},
}

@article {pmid42792229,
year = {2026},
author = {Butterfield, DA},
title = {Oxidative Stress and Its Mitigation in Neurodegenerative Disorders.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/antiox15091190},
pmid = {42792229},
issn = {2076-3921},
abstract = {There is significant evidence that, in neurodegenerative disorders, oxidative stress in the brain is fundamental to the pathophysiology and progression of such conditions, among which is Alzheimer disease (AD) [...].},
}

@article {pmid42792773,
year = {2026},
author = {Shah, KC and Littlestone, E and Ahmmad, MR and Wang, C and Xu, Y and Zhang, X},
title = {A Cross-Region Meta-Analysis and Machine Learning Identifies a 37-Gene Signature Associated with Alzheimer's Disease.},
journal = {Biomedicines},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/biomedicines14092032},
pmid = {42792773},
issn = {2227-9059},
support = {//University of South Florida/ ; },
abstract = {Background/Objectives: Alzheimer's disease (AD) shows marked transcriptomic heterogeneity across brain regions, limiting reproducibility. We aimed to identify robust cross-region gene signatures using meta-analysis. Methods: Differential expression (limma-voom) was performed on five bulk RNA-seq datasets (n = 230; 154 AD donors, 76 controls) from the hippocampus to cortical regions. Consensus DEGs were identified via Stouffer's Z, random effects, and MetaVolcanoR models. Pathway enrichment and associations with Braak stage were evaluated. Validation was conducted in two independent cohorts, with predictive performance assessed using machine learning. Results: Thirty-seven consensus DEGs (16 up, 21 down; FDR ≤ 0.05) were identified across ≥4 datasets. The enrichment results revealed increased expression of glial and ECM-associated genes and decreased expression of synaptic and GABAergic genes. Thirty-six of 37 genes correlated with Braak stage, with all 37 remaining significantly associated after covariate adjustment. The signature predicted AD with AUCs of 0.784 and 0.861 for validation in two independent cohorts. Conclusions:: We identified a consistent cross-region signature linking synaptic and glial changes to neuropathological severity, highlighting new mechanisms and potential biomarkers.},
}

@article {pmid42792797,
year = {2026},
author = {Kaveh, R and Kamari, F and Høilund-Carlsen, PF and Blaabjerg, M and Christensen, AA and Poulsen, FR and Ghaedi, S and Alavi, A and Andalib, S},
title = {Traumatic Brain Injury and the Road to Alzheimer's Disease.},
journal = {Biomedicines},
volume = {14},
number = {9},
pages = {},
doi = {10.3390/biomedicines14092056},
pmid = {42792797},
issn = {2227-9059},
abstract = {Alzheimer's disease (AD) is associated with both mild and moderate to severe traumatic brain injury (TBI). This narrative review gives an account of the association of TBI and AD and highlights possible cellular and molecular pathways linking these pathologies. Following TBI, the immune system of the brain is rapidly activated and gives rise to acute neuroinflammation. While neuroinflammation is protective in nature, it may persist chronically in the case of less-controlled prolonged responses, triggering neuroprotective loss and neurotoxicity. Moreover, reduced clearance of amyloid-beta may occur, along with its overproduction and aggregation. Tau protein regulation is also altered by kinase and phosphatase enzymes, resulting in the accumulation of hyperphosphorylated tau protein in neurons and glial cells and the emergence of intracellular tau neurofibrillary tangles. More to the point, vascular impairment following TBI has been reported to contribute to cognitive decline and AD. Blood-brain barrier breakdown following TBI allows for infiltration of peripheral immune cells and blood-derived proteins into the brain, which exacerbates neuroinflammation, interrupts synaptic signaling, and promotes oxidative stress. The neuroinflammatory response, dynamic alterations in amyloid and tau biology, and vascular impairment are thought to interact within a broader network of processes associated with AD neurodegeneration, rather than acting as isolated mechanisms.},
}

@article {pmid42792975,
year = {2026},
author = {Luo, Y and Deng, J and Loh, Y and Lu, H and Wang, N and Tang, C and Zhang, B},
title = {Identification and Validation of the Nrf2/Slc2a1 Axis in Alzheimer's Disease.},
journal = {Genes},
volume = {17},
number = {9},
pages = {},
doi = {10.3390/genes17091081},
pmid = {42792975},
issn = {2073-4425},
support = {//Talent-Bidding Project for Key Tasks of the First Clinical Medical College of Guangzhou University of Chinese Medicine/ ; },
mesh = {*NF-E2-Related Factor 2/metabolism/genetics ; *Alzheimer Disease/metabolism/genetics/pathology ; Animals ; Oxidative Stress ; Signal Transduction ; Humans ; Hippocampus/metabolism/pathology ; Mitochondria/metabolism/pathology ; Disease Models, Animal ; Neurons/metabolism/pathology ; Mice ; Male ; Reactive Oxygen Species/metabolism ; },
abstract = {Background/Objects: Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive decline. Although Nrf2 is a key regulator of oxidative stress in AD, the molecular factors associated with Nrf2 signaling and their potential regulatory relationships remain incompletely understood. This study aimed to systematically identify and validate a novel Nrf2-associated signaling axis in AD. Results: Slc2a1 was identified as a key Nrf2-associated candidate gene. In the SCOP-induced AD model, reduced Nrf2 expression was accompanied by decreased Slc2a1 expression, cognitive impairment, hippocampal neuronal injury, excessive ROS accumulation, and mitochondrial abnormalities. Pharmacological modulation of Nrf2 was associated with corresponding changes in Slc2a1 expression, while Nrf2 activation was accompanied by improvements in oxidative stress and neuronal injury. Conclusions: This study identifies a potential functional relationship between Nrf2 signaling and Slc2a1 expression in AD-related pathology and proposes the Nrf2/Slc2a1 pathway as a potential mechanistic framework linking oxidative stress to mitochondrial abnormalities.},
}

*NF-E2-Related Factor 2/metabolism/genetics
*Alzheimer Disease/metabolism/genetics/pathology
Animals
Oxidative Stress
Signal Transduction
Humans
Hippocampus/metabolism/pathology
Mitochondria/metabolism/pathology
Disease Models, Animal
Neurons/metabolism/pathology
Mice
Male
Reactive Oxygen Species/metabolism

@article {pmid42793029,
year = {2026},
author = {Rafique, A and Farooq, A and Cho, CE and Bakovic, M},
title = {Epigenomic Remodeling by Lipid Metabolism: A Cross-Disease Perspective on Cancer and Brain Disorders.},
journal = {Genes},
volume = {17},
number = {9},
pages = {},
doi = {10.3390/genes17091134},
pmid = {42793029},
issn = {2073-4425},
support = {450256/CAPMC/CIHR/Canada ; },
mesh = {Humans ; *Lipid Metabolism/genetics ; *Neoplasms/genetics/metabolism/pathology ; *Epigenesis, Genetic ; Animals ; *Chromatin Assembly and Disassembly ; *Brain Diseases/genetics/metabolism ; Epigenomics ; },
abstract = {Lipid metabolism is no longer viewed simply as a source of membrane biomass or ATP. It is now proposed as a regulatory system that determines which metabolites reach the nucleus, which chromatin-modifying enzymes are engaged, and which transcriptional states become stable during disease progression. This review develops a mechanistic cross-disease framework emphasizing metabolite flux, subcellular compartmentalization, cell-type specificity, and the temporal persistence of chromatin states. We synthesize recent evidence linking lipid metabolism to chromatin remodeling in cancer, Alzheimer's disease, and Parkinson's disease, and we highlight how emerging single-cell multi-omics and spatial lipidomics may shape potential metabolism-targeted epigenetic therapies. In both cancer and brain disorders, lipid flux alters the availability of acetyl-CoA, S-adenosylmethionine, NAD+, and bioactive fatty acid derivatives, thereby reshaping histone acetylation, DNA and histone methylation, chromatin accessibility, and transcription-factor activity. In cancer, de novo lipogenesis, acetate scavenging, fatty acid oxidation, and phospholipid remodeling sustain nuclear acetyl-CoA pools, promote oncogenic super-enhancers, and support survival under hypoxia, acidosis, and therapy stress. In neurodegenerative disease, mitochondrial dysfunction, cholesterol dyshomeostasis, sphingolipid imbalance, oxysterol accumulation, and microglial lipid droplet formation may distort the epigenetic programs required for neuronal maintenance, synaptic plasticity, and inflammatory resolution. However, neurodegenerative disorders are not uniformly hypoacetylated; instead, they exhibit stage-, region- and cell-type-specific chromatin remodeling, with hypoacetylation at some vulnerable loci coexisting with hyperacetylation at others. By comparing lipid-epigenome coupling across proliferative and degenerative conditions, we argue that the same metabolic nodes can yield markedly different pathological outcomes depending on cellular context, providing a basis for more precise therapeutic design.},
}

Humans
*Lipid Metabolism/genetics
*Neoplasms/genetics/metabolism/pathology
*Epigenesis, Genetic
Animals
*Chromatin Assembly and Disassembly
*Brain Diseases/genetics/metabolism
Epigenomics

@article {pmid42793080,
year = {2026},
author = {Yam, ATY and Chai, YL and Hilal, S and Yuan, C and Mok, VCT and Venketasubramanian, N and Tan, BY and Sim, MA and Lai, MKP and Chen, CP and Chong, JR},
title = {Decreased Plasma IGF-1 Is Associated with Cortical Atrophy, but Not Concomitant Cerebrovascular Disease in Alzheimer's Dementia.},
journal = {Biomolecules},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/biom16091248},
pmid = {42793080},
issn = {2218-273X},
support = {MOH-000707-01//National Medical Research Council/ ; HLTRP/2022/PS-01//National University of Singapore/ ; },
mesh = {Humans ; *Alzheimer Disease/blood/pathology/complications/diagnostic imaging ; *Insulin-Like Growth Factor I/metabolism/analysis ; *Cerebrovascular Disorders/blood/complications/pathology ; Atrophy/blood ; Female ; Male ; Aged ; Biomarkers/blood ; Middle Aged ; },
abstract = {Dysregulated insulin signaling in the brain has been linked to cognitive impairment and dementia. Insulin-like growth factor 1 (IGF-1) is a peptide growth hormone crucial for neurogenesis and neuroprotection. Findings regarding potential involvement of IGF-1 in dementia have been conflicting, and the status of IGF-1 in clinical cohorts with Alzheimer's disease (AD) and concomitant cerebrovascular disease (CeVD) burden is unknown. A Singapore-based memory clinic cohort consisting of 46 non-cognitively impaired (NCI), 101 with cognitive impairment, no dementia (CIND) and 81 AD dementia subjects underwent plasma IGF-1 measurements and neuroimaging assessments for association analyses of peripheral IGF-1 with regional brain volumes, as well as with neuroimaging CeVD markers (lacunes, cerebral microbleeds, white matter hyperintensities). Plasma IGF-1 levels were significantly lower in AD compared to NCI and CIND participants (both p < 0.001). Plasma IGF-1 was significantly associated with smaller hippocampal (p = 0.035), amygdala (p = 0.024), parietal lobe (p = 0.029), and frontal lobe (p = 0.002) volumes. In contrast, plasma IGF-1 did not associate with CeVD markers after covariate adjustments. Our findings suggest that plasma IGF-1 may be a blood-based biomarker for reduced brain volumes, while having no direct role in CeVD pathophysiology.},
}

Humans
*Alzheimer Disease/blood/pathology/complications/diagnostic imaging
*Insulin-Like Growth Factor I/metabolism/analysis
*Cerebrovascular Disorders/blood/complications/pathology
Atrophy/blood
Female
Male
Aged
Biomarkers/blood
Middle Aged

@article {pmid42793112,
year = {2026},
author = {Górecki, K and Polakowski, J and Więckowska, N and Grzywa, R and Frączyk, J and Kolesińska, B and Wróbel-Tałałaj, A and Drozdowska, D and Janczewski, Ł},
title = {Design, Synthesis, and Biological Activity of Isothiocyanate-Triazine Conjugates as AChE and BACE1 Inhibitors.},
journal = {Biomolecules},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/biom16091280},
pmid = {42793112},
issn = {2218-273X},
support = {W3/5P/2022//Lodz University of Technology/ ; W-3D/FMN/5G/2022//Lodz University of Technology/ ; },
mesh = {*Triazines/chemistry/pharmacology/chemical synthesis ; *Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism/chemistry ; *Cholinesterase Inhibitors/chemical synthesis/chemistry/pharmacology ; *Aspartic Acid Endopeptidases/antagonists & inhibitors/metabolism/chemistry ; *Acetylcholinesterase/metabolism/chemistry ; *Isothiocyanates/chemistry/pharmacology/chemical synthesis ; Animals ; Humans ; *Drug Design ; Molecular Docking Simulation ; },
abstract = {The search for new compounds capable of inhibiting the activity of enzymes involved in the development of neurodegenerative diseases, including Alzheimer's disease, has attracted continuing interest for many years. Natural isothiocyanates and their synthetic analogs, as well as compounds containing a 1,3,5-triazine core, constitute a group of molecules with complex mechanisms of action involving multiple molecular targets. Although literature data confirm the activity of both isothiocyanates and s-triazines, these two active fragments have not yet been combined, and it remains unclear whether a synergistic effect can be achieved. In this study, 11 novel isothiocyanate-triazine conjugates, consisting of a 1,3,5-triazine core substituted with aliphatic or cyclic secondary amines and a phosphorus analogue of isothiocyanate [6-(isothiocyanatohexyl)phosphonate)ethyl], were synthesized with yields of 46-80%. The pharmacokinetic profiles and parameters related to Lipinski's rule of five were determined for all compounds. All compounds were evaluated as inhibitors of acetylcholinesterase (AChE) and β-secretase (BACE1). Compound 1i showed the highest inhibitory activity against AChE (IC50 = 0.182 ± 0.02 µM), while compound 1b exhibited the strongest inhibition of BACE1 (IC50 = 8.48 ± 2.18 µM). To explore the potential of these multifunctional derivatives, plausible enzyme-ligand binding models were proposed based on molecular docking simulations.},
}

*Triazines/chemistry/pharmacology/chemical synthesis
*Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism/chemistry
*Cholinesterase Inhibitors/chemical synthesis/chemistry/pharmacology
*Aspartic Acid Endopeptidases/antagonists & inhibitors/metabolism/chemistry
*Acetylcholinesterase/metabolism/chemistry
*Isothiocyanates/chemistry/pharmacology/chemical synthesis
Animals
Humans
*Drug Design
Molecular Docking Simulation

@article {pmid42793168,
year = {2026},
author = {Khan, AM and García-Ayllón, MS and Hollings, O and Garcia-Ratés, S and Greenfield, S},
title = {A Novel Regulatory System in Brain Development and Death Driven by a Bioactive Peptide Linked to a Specific Isoform of Acetylcholinesterase.},
journal = {Biomolecules},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/biom16091336},
pmid = {42793168},
issn = {2218-273X},
support = {PI17/0026//FEDER/ ; },
mesh = {Animals ; *Acetylcholinesterase/metabolism/genetics/chemistry ; *Brain/growth & development/metabolism/embryology ; *Peptides/metabolism ; Humans ; Rats ; Mice ; Alzheimer Disease/metabolism/pathology ; },
abstract = {BACKGROUND: Acetylcholinesterase (AChE) demonstrates non-enzymatic actions attributable to a 14mer bioactive peptide derived from its sixth exon, 'T14', a pivotal agent driving Alzheimer's disease (AD).

METHODS: To investigate this possible parallel between development and neurodegeneration, we tracked the expression and timeline of T14 in embryonic and neonatal rodent brain tissue in relation to the expression of its parent molecule, AChE, benchmarked against markers of neural maturation (NeuN) and neurodegenerative pathology (pTau) using sedimentation profiling, Western blotting, and qPCR.

RESULTS: We report two key findings: Firstly, while overall AChE activity, expression, and oligomeric assembly in the developing rodent cortex predominantly reflect AChE-T, endogenous T14 appear to selectively correspond with the AChE-R variant (r = 0.936, p = 0.0639), peaking at P7 before declining in tandem with NeuN and pTau. Secondly, application of exogenous peptide to cultured SHSY-5Y cells triggers the selective upregulation of this same variant, AChE-R (F(3,18) = 9.320, p < 0.05). This effect is blocked by cotreatment with either mTORC1 inhibitor rapamycin or NBP14, an antagonist of T14.

CONCLUSIONS: We conclude that in development, T14 and AChE-R are closely linked, that both are involved in a developmental mechanism most active in the embryonic brain, and that inappropriate reactivation of this mechanism in the mature brain could be the driver in the progression of AD.},
}

Animals
*Acetylcholinesterase/metabolism/genetics/chemistry
*Brain/growth & development/metabolism/embryology
*Peptides/metabolism
Humans
Rats
Mice
Alzheimer Disease/metabolism/pathology