@article {pmid41813153,
year = {2026},
author = {Panek, S and Van Baelen, AC and Volta, BD and Dutta, SB and Hericks, L and Karoui, R and Vortmeyer, E and Hannappel, Y and Dodero, VI and Huser, T and Servent, D and Lequin, O and Kapurniotu, A and Sewald, N and Tonali, N},
title = {Cyclopeptide-Based Fluorescent Conjugates for Monitoring Prefibrillar Aβ Nanostructures.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.6c00059},
pmid = {41813153},
issn = {1520-4804},
abstract = {Amyloid-β (Aβ1-42) prefibrillar aggregates are considered the most neurotoxic amyloid species, yet their transient and heterogeneous nature makes selective detection challenging. Many fluorescent probes also fail to discriminate Aβ from homologous peptides such as IAPP, leading to poor specificity. We report a peptide-guided late-stage diversification strategy to generate BODIPY-based probes highly selective for prefibrillar Aβ1-42. A rationally engineered cyclic peptide derived from the C-terminal region of Aβ1-42 provides conformational rigidity and precise molecular recognition. Conjugation to BODIPY fluorophores afforded peptide-dye hybrids systematically evaluated for selectivity and photophysical response. A controlled aggregation protocol enabling reproducible generation of prefibrillar Aβ species was established to validate probe performance. A Sonogashira-derived conjugate (probe 8) showed strong fluorescence turn-on and selective affinity for prefibrillar Aβ1-42, with no response to IAPP aggregates. In neuronal cells, probe 8 outperformed conventional antibodies, supporting its potential for mechanistic studies and early Alzheimer's disease diagnostics.},
}

@article {pmid41813040,
year = {2026},
author = {Araujo, AQC},
title = {The corporate takeover of Alzheimer's treatment: a crisis in neurological autonomy?.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {3},
pages = {1-5},
doi = {10.1055/s-0046-1817020},
pmid = {41813040},
issn = {1678-4227},
abstract = {The recent approval of monoclonal antibodies for the treatment of Alzheimer's disease represents a significant advancement in neurology. This accomplishment coincides with a worrisome trend: the increasing hegemony of large corporate healthcare organizations and commercial laboratory corporations in the supply of these new medications. This editorial examines how corporate influence undermines the traditional physician-patient relationship, diminishes neurologist autonomy, and signals a broader incursion into neurological practice by nonspecialists. The current situation in Brazil, compared with the United States and Europe, including the United Kingdom, is discussed, and strategies are proposed to maintain the integrity of neurological therapy amid growing corporate influence in the medical field.},
}

@article {pmid41813037,
year = {2026},
author = {Ribeiro, IC and Gonçalves, BC and Aventurato, ÍK and Silva, MCRD and Rizzi, L and Rochetti, ALG and Fernandes, GBP and Cendes, F and Balthazar, MLF},
title = {Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology.},
journal = {Arquivos de neuro-psiquiatria},
volume = {84},
number = {3},
pages = {1-9},
doi = {10.1055/s-0046-1817040},
pmid = {41813037},
issn = {1678-4227},
mesh = {Humans ; *Alzheimer Disease/physiopathology/pathology/diagnostic imaging ; Male ; Female ; Aged ; Magnetic Resonance Imaging ; *Cognitive Dysfunction/physiopathology/diagnostic imaging/pathology ; Neuropsychological Tests ; *Cognition/physiology ; Biomarkers/cerebrospinal fluid ; Aged, 80 and over ; Disease Progression ; Middle Aged ; Brain/pathology ; Reference Values ; },
abstract = {The diagnosis of predementia stages indicates an increased risk of progression to dementia. The Amyloid, Tau, and Neurodegeneration AT(N) classification considers measurements of altered proteins and the presence of neurodegeneration to classify the risk groups regarding the pathophysiology of Alzheimer's disease (AD). The cognitive and anatomical characteristics of the patients in the predementia stage according to the AT(N) classification are not fully understood.To investigate whether there are differences in the clinical and anatomical profiles among older adults in the predementia stage according to the ATN classification, and to investigate the associations involving cognition and cortical thickness and subcortical volume in the AT(N) groups.In total, 72 older adults with subjective cognitive decline and mild cognitive impairment were allocated to groups according to the AT(N) classification (AD continuum: n = 37; suspected non-AD pathophysiology: n = 8; normal biomarkers: n = 27). The participants were investigated through cognitive tests, magnetic resonance imaging scans, and cerebrospinal fluid analyses. We used multivariate and univariate analyses with post-hoc testing to verify differences among groups. In addition, linear regressions were performed to verify the interactions involving cognition and gray matter metrics.The suspected non-AD pathophysiology group showed worse performance in attention/executive function than the AD continuum and normal biomarkers groups (p = 0.04). However, the ATN classification groups did not differ in terms of cortical thickness (p > 0.05). In addition, in the AD continuum group, memory was associated with left fusiform gyrus thickness (p = 0.000 uncorrected; r = 0.238).Cognition, but not gray matter metrics, differs among AT(N) classification groups. Memory is associated with cortical thickness in patients with positive amyloid Beta (AD continuum).},
}

Humans
*Alzheimer Disease/physiopathology/pathology/diagnostic imaging
Male
Female
Aged
Magnetic Resonance Imaging
*Cognitive Dysfunction/physiopathology/diagnostic imaging/pathology
Neuropsychological Tests
*Cognition/physiology
Biomarkers/cerebrospinal fluid
Aged, 80 and over
Disease Progression
Middle Aged
Brain/pathology
Reference Values

@article {pmid41812941,
year = {2026},
author = {Wang, M and Niu, D and Zhang, Q and Tang, Y and Zhao, Y and Chen, F},
title = {CRISPR-based correction of apolipoprotein E4 in Alzheimer's disease: Therapeutic strategies and macromolecular delivery innovations.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {151352},
doi = {10.1016/j.ijbiomac.2026.151352},
pmid = {41812941},
issn = {1879-0003},
abstract = {Alzheimer's disease (AD) is the leading cause of dementia worldwide, with substantial unmet clinical needs. The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for late onset AD, with each copy increasing risk approximately two- to three-fold, and homozygous carriers facing up to a 10- to 15-fold higher risk compared to APOE3 carriers. APOE4 contributes to diverse pathogenic mechanisms including lipid dysregulation, neuroinflammation, synaptic dysfunction, and vascular compromise. The precise, allele-specific correction of APOE4 therefore holds transformative therapeutic potential. CRISPR-based genome editing technologies, including nuclease disruption, base editing, and prime editing, offer unprecedented opportunities to directly modify APOE4 at its genomic source. Here, we review mechanistic underpinnings of APOE4 pathology, summarize current gene editing platforms for APOE4 correction, evaluate relevant in vitro and in vivo model systems, and assess delivery strategies with an emphasis on nanoparticle and exosome based approaches. We highlight recent breakthroughs in exosome mediated APOE4 editing while addressing ongoing technical hurdles in allele specificity and translational barriers such as Cas nuclease immunogenicity, limited delivery efficiency across the blood brain barrier (BBB), and concerns over long term genomic safety. This review concludes that overcoming BBB constraints remains the most significant challenge for clinical translation, and that innovations in exosome and nanoparticle based delivery platforms represent the most promising strategies for advancing CRISPR therapeutics for AD.},
}

@article {pmid41812935,
year = {2026},
author = {Chauhan, P and Wadhwa, K and Singh, G},
title = {Rosa × damascena Herrm. and Commiphora wightii (Arn.) Bhandari. combination therapy ameliorates cognitive, neurobehavioral and metabolic impairments in a rat model of Alzheimer's disease through restoration of mitochondrial functions, regulation of neurotransmitter balance and attenuation of pro-inflammatory cytokine levels.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121509},
doi = {10.1016/j.jep.2026.121509},
pmid = {41812935},
issn = {1872-7573},
abstract = {Rosa × damascena Herrm. has been widely employed in Iranian traditional medicine as a nerve tonic to treat anxiety, depression, headache, and other neurological disorders. Additionally, Commiphora wightii (Arn.) Bhandari. (Guggul) is also well recognized in both Ayurvedic and Unani systems, used to treat lipid disorders, obesity, facial paralysis, tremors, and memory loss.

AIM OF THE STUDY: Although traditionally used individually, the combination represents a rational multi-target strategy to simultaneously address metabolic and neurodegenerative components associated with Alzheimer's disease (AD). Thus, the present study explored the neuroprotective, metabolic, and behavioral effects of R. damascena and C. wightii combination therapy in a streptozotocin (STZ)-induced rat model of AD.

MATERIAL AND METHODS: Adult Wistar rats were administered intracerebroventricular STZ to induce AD-like pathology. A dose-response and combination screening study was initially performed to identify an optimal R. damascena - C. wightii dose pair using normalized escape latency and interaction analysis. The best identified combination and its associated per se doses were then subsequently subjected to detailed behavioral and biochemical evaluations.

RESULTS: The interaction-guided analysis identified R. damascena 600 mg/kg + C. wightii 400 mg/kg as the most effective combination and utilized further. While both extracts alone exerted significant protective effects, their combined intervention was more effective in restoring metabolic homeostasis, enhancing motor coordination and exploratory activity, reducing anxiety-like behavior, and improving spatial learning and memory compared to monotherapy, primarily through attenuation of oxidative stress, inhibition of TNF-α-associated neuroinflammatory cascades, restoration of mitochondrial function, and normalization of glutamatergic and cholinergic neurotransmission.

CONCLUSION: The findings support this combination as a promising herbal strategy for further investigation in the management of metabolic and cognitive disturbances associated with AD.},
}

@article {pmid41812924,
year = {2026},
author = {Shi, Z and Hao, M and Chen, G and Li, F and Zhou, Y and Zhou, JC},
title = {Phosphatidylethanolamine: Its biological significance and responses to nutritional factors for neurohealth.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101468},
doi = {10.1016/j.tjnut.2026.101468},
pmid = {41812924},
issn = {1541-6100},
abstract = {Phosphatidylethanolamine (PE) is a major component of biological membranes, pivotal to numerous life processes. Inhibition of its synthesis via either the CDP-ethanolamine (Kennedy) pathway or the phosphatidylserine decarboxylation pathway can be lethal. PEs derived from different organelles have different functions and biological significance, so they are not fully interchangeable. From a biological perspective, PE is involved in constructing membranes and plays a crucial part in mitochondrial biogenesis, ferroptosis, cell autophagy, cell division, synthesis of biomolecules, and other processes. Furthermore, PE acts as the essential substrate for glycosylphosphatidylinositol anchor biosynthesis, thereby governing processes such as immune response, signal transduction, and embryonic development. Notably, PE is highly enriched in neural tissues and is closely implicated in the pathology of multiple neurological disorders, including hereditary spastic paraplegia, Liberfarb syndrome, Alzheimer's disease, Parkinson's disease, and sepsis-associated encephalopathy. Given that the levels, composition, and functions of PE can be modulated by dietary and nutritional factors, including polyunsaturated fatty acids, specific minerals and vitamins, and dietary patterns, targeting PE metabolism represents a promising and translatable strategy for supporting neurological health. This approach holds potential not only for populations with or at risk for neurodegenerative disorders but also for developing fetuses and newborns during critical nervous system development. This review summarizes recent advances in these areas, updates our understanding of PE's basic biology, and explores novel strategies for neuroprotection and health promotion.},
}

@article {pmid41812842,
year = {2026},
author = {Jali, V and Li, L and Qi, TA and Tanaka, T and Hilal, S and Gyanwali, B and Chen, CL and Ngam, PI},
title = {Comparative Analysis of Heuron Brain PET and FreeSurfer Software in Automated Amyloid Quantification: Toward Reproducible and Clinically Applicable Brain PET Imaging.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {121844},
doi = {10.1016/j.neuroimage.2026.121844},
pmid = {41812842},
issn = {1095-9572},
abstract = {PURPOSE: Beta-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer's disease (AD) and can be evaluated using positron emission tomography (PET). While visual assessment is standard in clinical settings, quantitative methods such as standardized uptake value ratios (SUVR) may improve diagnostic accuracy and reproducibility. This study aimed to compare the quantification and diagnostic performance of Heuron Brain PET, a recently developed clinical tool, with FreeSurfer, a well-validated research platform, in assessing Aβ deposition.

METHODS: A total of 205 amyloid PET scans (176 [¹¹C]PiB + 29 [¹⁸F]Flutafuranol) were analyzed using both Heuron Brain PET and FreeSurfer. SUVRs were calculated using cerebellar grey matter as the reference region. Diagnostic thresholds were determined, and regional/global SUVRs were compared using paired t-tests and correlation analysis. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Reproducibility was assessed on a randomly selected subset (n=50) using intraclass correlation coefficients (ICC).

RESULTS: For [¹¹C]PiB, Heuron Brain PET yielded slightly lower global SUVRs than FreeSurfer (1.32 ± 0.34 vs. 1.40 ± 0.41; p < 0.001), but showed very strong correlation (r = 0.960, p < 0.001). AUCs were comparable (Heuron: 0.988; FreeSurfer: 0.979; p = 0.401). ICC for reproducibility was perfect across all regions (ICC = 1.00, 95% CI [1.00, 1.00], p < 0.001). Results for [¹⁸F]Flutafuranol were less consistent due to small sample size.

CONCLUSION: Heuron Brain PET demonstrates comparable SUVR quantification and diagnostic performance to FreeSurfer for [¹¹C]PiB PET, with excellent reproducibility and rapid analysis, supporting its potential for routine clinical application.},
}

@article {pmid41812815,
year = {2026},
author = {Shen, X and Dong, X and Nao, J},
title = {Harmine and its derivatives: A promising multi-target therapeutic avenue for Alzheimer's disease.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.03.006},
pmid = {41812815},
issn = {1873-7544},
abstract = {Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, tau hyperphosphorylation, neuroinflammation, and cholinergic dysfunction. Currently, no disease-modifying drugs are available, and existing symptomatic treatments offer limited efficacy while posing safety concerns, highlighting the urgent need for multi‑target therapeutic strategies. The natural β‑carboline alkaloid harmine has attracted considerable attention due to its favorable blood-brain barrier penetration and multi‑target profile. Accumulating preclinical evidence indicates that harmine can concurrently modulate several core pathological processes of AD. Mechanistically, it potently inhibits dual‑specificity tyrosine phosphorylation‑regulated kinase 1A (DYRK1A), thereby reducing tau hyperphosphorylation, suppressing aberrant amyloid precursor protein processing, and enhancing neprilysin‑mediated Aβ clearance. Concurrently, harmine attenuates neuroinflammation via negative regulation of the Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF‑κB) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathways, improves cholinergic neurotransmission through acetylcholinesterase inhibition, and alleviates glutamate excitotoxicity by upregulating astrocytic glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) expression. Structurally optimized harmine derivatives have demonstrated enhanced dual inhibitory activity and improved cognitive outcomes in preclinical models. Despite these promising findings, challenges such as pharmacokinetic limitations, insufficient target selectivity, and a lack of clinical data remain. In conclusion, the harmine scaffold represents a mechanistically grounded and promising direction for the development of multi‑target therapeutics for AD.},
}

@article {pmid41812704,
year = {2026},
author = {Wang, J and Wang, B and Zhu, K and Zhang, J and Zhang, G and Liu, S and Dasun Vimukthi, WP and Zhang, Y and Cao, F and Yang, C and Sun, X},
title = {Indoor aerosols induced blood-brain barrier leakiness and β-amyloid1-42 aggregation.},
journal = {Journal of advanced research},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jare.2026.03.015},
pmid = {41812704},
issn = {2090-1224},
abstract = {INTRODUCTION: Exposure to indoor aerosols that include fine particulate matter 2.5 (PM2.5) and microorganisms has been implicated in various health issues, including neurodegenerative diseases.

OBJECTIVES: The major components of indoor aerosols could induce the blood-brain barrier (BBB) leakiness and β amyloid (Aβ) aggregation, potentially exacerbating Alzheimer's disease (AD) pathology.

METHODS: The main components of aerosols were collected by an intelligent sampler and an airborne microorganism sampler, respectively. The PM2.5 was characterized with SEM and UV-vis spectrophotometer. The microorganisms were identified by 16S rRNA gene sequencing. The Aβ aggregation was studied by thioflavin T kinetic assay and circular dichroism spectroscopy. The BBB models were constructed by seeding astrocytes and human brain microvascular endothelial cells on the membrane of transwell inserts. Moreover, the BBB leakiness induced by PM2.5, Staphylococcus aureus (S. aureus), and the Aβ aggregates was evaluated by immunofluorescence imaging and transwell assay both in vitro and in vivo.

RESULTS: The PM2.5 owns the size of 112 ± 35.41 nm and the surface charge of -0.125 mV. PM2.5 and S. aureus can independently disrupt the BBB integrity both in vitro and in vivo by down-regulating adherens and tight junction proteins including zonula occludens-1, VE-cadherin, occludin, and claudin-5. Furthermore, PM2.5 and S. aureus accelerated Aβ aggregation into neurotoxic oligomers and fibrils. In combined exposures, PM2.5 + Aβ or S. aureus + Aβ act synergistically to exacerbate BBB permeability and cytotoxicity of endothelial cells, astrocytes, and neuron cells, creating a vicious cycle of the BBB dysfunction and neurodegeneration.

CONCLUSIONS: These findings establish PM2.5 and S. aureus as dual environmental drivers of BBB compromise and Aβ pathology, offering novel mechanistic insights and emphasizing the urgent need for strategies to mitigate indoor aerosol-related health risks for AD patients.},
}

@article {pmid41812658,
year = {2026},
author = {Turnbull, A and Gross, JJ and Vankee-Lin, F},
title = {The emergence of neuropsychiatric symptoms in preclinical Alzheimer's disease: An emotion regulation perspective.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.01.022},
pmid = {41812658},
issn = {1097-4199},
abstract = {Preclinical Alzheimer's disease (AD) is associated with distressing neuropsychiatric symptoms (NPSs) that may accelerate progression toward dementia. Existing approaches probe the symptom-level domain-general or domain-specific neural correlates of NPSs. However, the field lacks process-oriented models of symptom emergence for targeted treatment. We propose one pathway for symptom emergence involving the disruption of emotion regulation (ER) systems by early AD pathology. AD pathology in the ventral anterior cingulate cortex-ventromedial prefrontal cortex disrupts model-free ER that modulates negative valuations using experience-dependent reinforcement learning (e.g., fear extinction), leading to increased negative valuations and negative affect. We further propose that model-based ER competes for overtaxed executive resources and is less successful in preclinical AD, particularly in demanding real-world contexts. These changes lead to a shift toward negative affect, leading to divergent trajectories of NPSs depending on critical moderators. We discuss implications for intervention to improve NPSs and potentially slow dementia progression.},
}

@article {pmid41812391,
year = {2026},
author = {Yilmaz, S and Aslam, S and Sillau, S and Katz, M and Kluger, B},
title = {Bridging the gap: Evaluating a community-based palliative care intervention for underserved patients with Parkinson's disease.},
journal = {Parkinsonism & related disorders},
volume = {146},
number = {},
pages = {108262},
doi = {10.1016/j.parkreldis.2026.108262},
pmid = {41812391},
issn = {1873-5126},
abstract = {BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative illness with a profound impact on quality of life (QOL). While palliative care has demonstrated benefits in PD, reach and evidence of effectiveness in underserved populations remain limited. The goal of this study was to evaluate the effect of a novel palliative care intervention on QOL among underserved patients with PD.

METHODS: We conducted a secondary analysis of data from a stepped-wedge, pragmatic clinical trial (NCT03076671) among 322 participants with PD. We created an "underserved demographic" composite variable based on rural residency, low income (<$50,000/year), and race/ethnicity (non-White or Hispanic). QOL was measured using the Quality of Life in Alzheimer's Disease Scale (QOL-AD) at baseline, 6 months, and 12 months. We used t-tests for group comparisons at baseline and linear mixed-effects models for longitudinal analyses.

RESULTS: A total of 129 participants were identified as underserved. The intervention showed significant improvement in QOL over time for non-underserved participants at 6 months (p = 0.06) and 12 months (p = 0.04). While overall improvements among underserved participants were not observed at earlier time points, we found a statistically significant time and group interaction effect suggesting a meaningful QOL improvement in the underserved group at 12 months compared to baseline (estimate = 2.39, 95% CI: 0.33-4.46, p = 0.05).

CONCLUSIONS: Findings suggest that this community-based palliative care intervention may help support improvements in QOL over time among underserved patients with PD. Tailored, longitudinal palliative care approaches may help bridge disparities in neurologic care.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03076671.},
}

@article {pmid41812151,
year = {2026},
author = {Yang, M and Li, Z and Xinhong Ye, K and Guo, J and Lee, TS and Cao, L and Wang, Y and Ye, R and Maier, AB and Feng, L and Chen, C},
title = {Dietary Factors and Cognitive Health in Ethnic Chinese: A Systematic Review and Meta-analysis.},
journal = {Nutrition reviews},
volume = {},
number = {},
pages = {},
doi = {10.1093/nutrit/nuag026},
pmid = {41812151},
issn = {1753-4887},
support = {2023HWYQ-017//Distinguished Young Scholars of the Natural Science Foundation of Shandong Program (Overseas)/ ; },
abstract = {CONTEXT: Dementia is a group of neurological disorders affecting millions worldwide, placing substantial strain on healthcare systems. Although diet has been identified as a modifiable risk factor for cognitive health in aging, there is limited research on how dietary patterns affect cognitive outcomes in ethnic Chinese populations. Chinese populations, primarily in Mainland China, Hong Kong, Macao, Taiwan, and Singapore, have distinct genetic profiles and diverse dietary traditions. These genetic and cultural dietary factors may interact in specific ways to influence cognitive health.

OBJECTIVE: This systematic review and meta-analysis critically evaluated the evidence on the dietary factors and cognitive health in the ethnic Chinese population.

DATA SOURCES: A systematic search of PubMed, Web of Science, Scopus, and CNKI were conducted according to the PRISMA criteria.

DATA EXTRACTION: Two reviewers independently extracted data using a standardized data extraction template. Information collected included study characteristics, participant demographics, dietary exposures or patterns, cognitive outcomes, and key findings. Study quality was assessed using the National Institutes of Health criteria for observational studies. Extracted data, including reported odds ratios (ORs) and corresponding 95% CIs, were summarized and used for subsequent analyses.

DATA ANALYSIS: Meta-analyses were performed using random-effects models to pool ORs with corresponding 95% CIs. Between-study heterogeneity was assessed using τ2 and I2 statistics, with I2 values >50% indicating substantial heterogeneity. Statistical significance was set at P < .05.

CONCLUSION: Evidence from observational studies suggests that dietary patterns rich in vegetables, fruits, fish, and plant-based foods are associated with a lower risk of cognitive decline in ethnic Chinese adults, potentially influenced by unique genetic variations, traditional dietary practices, and cultural factors. Adherence to the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets, as well as higher consumption of mushrooms and tea, was linked to better cognitive health, whereas diets high in red meat and low in fish and legumes were associated with increased risk. Meta-analysis showed a protective association for plant-based diets (OR: 0.78; 95% CI: 0.69-0.87).

PROSPERO NO. CRD42024575522.},
}

@article {pmid41811933,
year = {2026},
author = {El-Sabbagh, NA and Ellakwa, DE},
title = {AMP-activated protein kinase as a therapeutic target: effects of nano-selenium and thymoquinone in Alzheimer's disease.},
journal = {Archives of physiology and biochemistry},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/13813455.2026.2640885},
pmid = {41811933},
issn = {1744-4160},
abstract = {CONTEXT: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and complex multifactorial pathogenesis. AMP-activated protein kinase (AMPK) has been identified as a promising molecular target in AD due to its neuroprotective functions, particularly in energy regulation.

OBJECTIVE: To evaluate the effects of nano-selenium and thymoquinone (TQ) on AMPK gene expression in an AD rat model.

SUBJECTS AND METHODS: Fifty male albino rats were divided into five groups. Four groups were induced with AD via lipopolysaccharide (LPS) injection, while the control group remained untreated. The experimental groups received nano-selenium, TQ, or a combination of both treatments. AMPK gene expression in brain tissue was measured using real-time PCR analysis.

RESULTS: Treatment with nano-selenium, TQ, or their combination significantly upregulated AMPK expression in brain tissue compared to untreated AD rats (p<0.001). The combination therapy produced the highest increase in AMPK expression.

DISCUSSION AND CONCLUSION: Nano-selenium and TQ enhance AMPK gene expression in AD, suggesting a potential therapeutic mechanism involving AMPK-related pathways.},
}

@article {pmid41811929,
year = {2026},
author = {Henao Isaza, V and Aguillon, D and Tobón-Quintero, CA and Lopera, F and Ochoa-Gómez, JF},
title = {Comprehensive methodology for sample enrichment in EEG biomarker studies for Alzheimer's risk classification.},
journal = {PloS one},
volume = {21},
number = {3},
pages = {e0343722},
doi = {10.1371/journal.pone.0343722},
pmid = {41811929},
issn = {1932-6203},
mesh = {Humans ; *Alzheimer Disease/diagnosis/physiopathology/genetics ; *Electroencephalography/methods ; Biomarkers ; Male ; Female ; Aged ; Middle Aged ; Presenilin-1/genetics ; Propensity Score ; },
abstract = {OBJECTIVE: Dementia, particularly Alzheimer's disease (AD), constitutes a major global health concern, with AD accounting for approximately 70% of all cases. EEG-based biomarkers hold promise for early identification of individuals at risk; however, small and heterogeneous samples frequently limit generalizability.

METHODS: An EEG-based sample enrichment framework was developed by integrating advanced signal processing, component-level feature extraction, data harmonization (neuroHarmonize), and Propensity Score Matching (PSM). EEG data from four independent cohorts were harmonized to reduce site-related variability while preserving covariates such as age and sex. Features including power, entropy, coherence, synchronization likelihood, and cross-frequency coupling were extracted from independent components. PSM was applied at 2:1, 5:1, and 10:1 ratios to expand and balance the control group (HC) relative to the Alzheimer's risk group (ACr), composed of PSEN1-E280A mutation carriers without cognitive symptoms.

RESULTS: Sample enrichment through PSM improved classification accuracy, with decision tree models yielding values between 0.91 and 0.96. Higher enrichment ratios enhanced model stability and generalizability, as shown by learning curves and confusion matrices. Feature selection was based on model performance and effect sizes (Cohen's d).

CONCLUSIONS: The proposed framework addresses sample size and variability constraints in EEG-based AD risk classification.

SIGNIFICANCE: Harmonization and statistical balancing provide a replicable strategy for multicenter EEG studies targeting early AD detection.},
}

Humans
*Alzheimer Disease/diagnosis/physiopathology/genetics
*Electroencephalography/methods
Biomarkers
Male
Female
Aged
Middle Aged
Presenilin-1/genetics
Propensity Score

@article {pmid41811667,
year = {2026},
author = {Li, D and Li, Y and Wen, L and Chen, Z and Gao, F and Shen, Y and Wang, Q},
title = {Astrocyte-Specific Upregulation of Tumor Necrosis Factor Receptor II Ameliorates Pathological Phenotypes in APP[NL-F/NL-F] Mice.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41811667},
issn = {1995-8218},
abstract = {Our earlier research showed that deletion of tumor necrosis factor-α receptor II (TNFRII) exacerbated Alzheimer's disease (AD) associated pathology in the AD mouse model. Previous studies have demonstrated that TNFRII was mainly expressed in astrocytes. However, whether AD-associated pathology can be modified by targeting TNFRII in astrocytes remains unknown. Here, we showed that TNFRII was decreased in astrocytes in AD brains. Then, we developed transgenic mouse models (astrocyte-specific expression of human TNFRII mice, TNFRII[GFAP] mice) and crossed TNFRII[GFAP] mice with a mouse model of AD (humanized APP knock-in mice, APP[NL-F/NL-F] mice). We found that increased expression of TNFRII in astrocytes rescued learning and memory deficits, decreased amyloid burden, and reactive astrocytes in APP[NL-F/NL-F] mice. Mechanistically, APP[NL-F/NL-F]-TNFRII[GFAP] mice displayed increased microgliosis, higher expression of plaque-associated microglial cluster of differentiation 68 (CD68), and enhanced microglial amyloid-β (Aβ) phagocytosis. In vitro assays confirmed that TNFRII upregulation in astrocytes enhanced phagocytosis of Aβ in BV2 murine microglial cell line (BV2) cells. Our study implicates that increased expression of TNFRII in astrocytes ameliorates pathology and behavioral deficits in APP[NL-F/NL-F] mice and provides new therapeutic options for AD.},
}

@article {pmid41811541,
year = {2026},
author = {Houfkova, A and Schmidt, M},
title = {Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer's Pathogenesis.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41811541},
issn = {1559-1182},
support = {SV2112/2024//Univerzita Hradec Králové, Czechia/ ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline, predominantly in the elderly (Alzheimer Disease International et al., 2015). Although amyloid-β peptide (Aβ), particularly in its oligomeric forms, has long been linked to AD pathogenesis (Chen 9:1205-1235 2017, Gaspar 2 394-400 2010), the mechanisms underlying its cellular toxicity remain unclear. Mitochondrial dysfunction is a consistent feature of AD (D'Alessandro 107:102713 2025), yet how Aβ drives these alterations is not fully understood. This review integrates recent evidence showing that Aβ accumulates on mitochondrial membranes (Cenini 21:3257-3272 2016, Manczak 23:5131-5146 2006, Sirk 5:1989-2003 2007), providing a mechanistic link between amyloid pathology and mitochondrial damage. We discuss how membrane-associated Aβ disrupts mitochondrial protein import by impairing the translocase of the outer membrane (TOM) complex (Cenini 21:3257-3272 2016, Sirk 5:1989-2003 2007) and interferes with voltage-dependent anion channel 1 (VDAC1) (Smilansky 52:30670-30683 2015), a key regulator of metabolite exchange and apoptosis. We further emphasize the role of mitochondria-associated membranes (MAMs) as critical sites for Aβ generation and transfer to mitochondria, where dysregulated cholesterol metabolism may amplify MAM activity and Aβ accumulation (Area-Gomez and Schon 38:90-96 2017, Monaghan 2:240287 2025). Altogether, we propose that mitochondrial membrane localization of Aβ is a central mechanism linking amyloid pathology to mitochondrial dysfunction in aging, highlighting new directions for mitochondria-targeted therapeutic strategies in AD.},
}

@article {pmid41811516,
year = {2026},
author = {Ting, SKS and Asahara Thio, S and Cao, K and Hameed, S and Li, W and Mukesh Shah, J and Lin, S and Sim, J and Chiew, HJ and Ng, KP and Ng, ASL},
title = {Early clinical characteristics of pathologically confirmed progressive supranuclear palsy and corticobasal degeneration.},
journal = {Journal of neurology},
volume = {273},
number = {3},
pages = {},
pmid = {41811516},
issn = {1432-1459},
support = {U24 AG072122/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Supranuclear Palsy, Progressive/pathology/diagnosis/complications/physiopathology ; Male ; Female ; Aged ; *Corticobasal Degeneration/diagnosis/pathology/physiopathology/complications ; Aged, 80 and over ; Middle Aged ; Depression/etiology ; },
abstract = {OBJECTIVES: Although the clinical features of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are well documented, their early clinical presentations from the perspective of initial clinical consultation remain less well understood. This study aimed to characterize the early clinical features of PSP and CBD to inform clinicians on diagnostic assessment and management strategies.

METHODS: Data were obtained from the National Alzheimer's Coordinating Center (NACC) database (2005-March 2025 data freeze). Neuropathologically confirmed cases of PSP (n = 278) and CBD (n = 149) were included. Analyses were restricted to first clinical visits, focusing on demographic, neuropsychiatric, neurological, and neuropsychological variables.

RESULTS: Memory symptoms were reported in more than half of both groups, whereas language impairment was more common in CBD (> 70%) and associated with higher odds of CBD diagnosis. Depression was frequent (~ 50%), with PSP showing higher odds for depressive symptoms but lower odds for disinhibition. Although 20-30% of both PSP and CBD patients exhibited no parkinsonian signs at presentation, gait disturbance, falls, and slowness were common and strongly associated with PSP. Approximately half of both groups presented with cognitive-predominant onset, and nearly one-fifth were initially misdiagnosed as Alzheimer's disease.

CONCLUSIONS: A substantial proportion of PSP and CBD patients lack parkinsonian signs at first presentation, and cognitive-onset presentations are frequent, leading to early diagnostic uncertainty. Clinicians should recognize these overlapping features when evaluating early atypical parkinsonian or cognitive syndromes.},
}

Humans
*Supranuclear Palsy, Progressive/pathology/diagnosis/complications/physiopathology
Male
Female
Aged
*Corticobasal Degeneration/diagnosis/pathology/physiopathology/complications
Aged, 80 and over
Middle Aged
Depression/etiology

@article {pmid41811463,
year = {2026},
author = {Zhang, T and Nie, B and Liu, H and Mao, G and OuYang, C and Jiang, X and Shan, B},
title = {Prediction of alzheimer's disease time to dementia onset using cross-sectional data from spatiotemporal biomarker progression patterns.},
journal = {European journal of nuclear medicine and molecular imaging},
volume = {},
number = {},
pages = {},
pmid = {41811463},
issn = {1619-7089},
support = {12205329//National Natural Science Foundation of China/ ; 12175268//National Natural Science Foundation of China/ ; X21520603//Ye Ming Han Fund/ ; E4545AU210//the Innovation Fund of the Institute of High Energy Physics, Chinese Academy of Sciences/ ; },
}

@article {pmid41811103,
year = {2026},
author = {Chen, Y and Ji, X and Zhao, J and Bao, Z and Huang, Y},
title = {SLC38A9 Regulation Affects Hippocampal Neuronal Autophagy: A Potential Alzheimer's Therapeutic Approach by Suppressing Alzheimer's Disease-Related Protein Deposition.},
journal = {CNS neuroscience & therapeutics},
volume = {32},
number = {3},
pages = {e70823},
doi = {10.1002/cns.70823},
pmid = {41811103},
issn = {1755-5949},
support = {82071581//National Natural Science Foundation of China/ ; 2022002//Shanghai Leading Talent Program/ ; 2023ZDFC0402//Shanghai Municipal Health Commission Key Support Discipline Program/ ; //China Youth Medical Innovation Research Project/ ; },
abstract = {AIMS: Impaired autophagy-mediated clearance of Alzheimer's disease (AD)-related proteins is a critical event in AD pathogenesis. SLC38A9, a member of the Solute Carrier 38 family, acts as an arginine sensor and plays an important role in regulating autophagy. Although the activation of autophagy regulated by the SLC38A9 may have a mitigating effect on AD, this aspect still awaits further exploration.

METHODS: APP/PS1 mouse models and HT22 cells treated with amyloid-β 25-35 (Aβ25-35) were transduced with vectors to evaluate the effect of SLC38A9 in AD.

RESULTS: We show that decreasing SLC38A9 could promote the hippocampal neuronal autophagic clearance of AD-related proteins, reduce neuronal apoptosis, and improve cognitive function.

CONCLUSION: Our results demonstrate SLC38A9 is involved in AD-related pathology and its cognitive impairment, and may offer new therapeutic targets to AD.},
}

@article {pmid41810694,
year = {2026},
author = {Yu, L and Yokomizo, S and Doan, TH and Zhao, Q and Ganne, A and Balasubramaniam, M and Kastanenka, KV},
title = {Zolpidem restores sleep and decreases amyloid in a mouse model.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71175},
doi = {10.1002/alz.71175},
pmid = {41810694},
issn = {1552-5279},
support = {R01AG066171/NH/NIH HHS/United States ; //Cure Alzheimer's Fund/ ; //Chan Zuckerberg Initiative DAF Fund/ ; //BrightFocus Foundation/ ; 202360054//Japan Society for the Promotion of Science/ ; PYJH2024314//Affiliated Hospital of Xuzhou Medical University/ ; },
mesh = {Animals ; *Zolpidem/pharmacology ; Mice ; Disease Models, Animal ; Mice, Transgenic ; *Alzheimer Disease/drug therapy ; *Sleep/drug effects ; *Plaque, Amyloid/pathology/drug therapy ; Electroencephalography ; Amyloid beta-Protein Precursor/genetics ; Brain/drug effects/metabolism ; Presenilin-1/genetics ; Male ; },
abstract = {INTRODUCTION: Deficits in non-rapid eye movement (NREM) sleep facilitate Alzheimer's disease (AD) progression. Enhancing gamma-aminobutyric acid-ergic (GABAergic) signaling can restore sleep. Unbiased computational analysis identified zolpidem as high-affinity GABA receptor modulator facilitating chloride transport that could slow AD.

METHODS: Zolpidem's effects on sleep and Alzheimer's progression were evaluated in young APP/PS1 (amyloid precursor protein/presenilin 1) mice. Sleep was monitored with electroencephalography/electromyography (EEG/EMG) telemetry. Wide-field imaging with voltage-sensitive dyes (VSDs) was used to track sleep-dependent brain rhythms. Multiphoton microscopy allowed assessments of amyloid plaque load and basal neuronal calcium levels. Behavioral assays were used to measure memory and cognitive function.

RESULTS: Zolpidem restored NREM sleep and rescued sleep-dependent brain rhythm, slow oscillation. Zolpidem administration reduced cortical amyloid plaque burden, mitigated neuronal calcium overload, and enhanced sleep-dependent contextual recall without adverse effects on locomotion.

DISCUSSION: Zolpidem effectively decreased amyloid in young APP/PS1 mice. This supports zolpidem's therapeutic promise as an intervention strategy at early stages of AD.

HIGHLIGHTS: Zolpidem treatment improves non-rapid eye movement (NREM) sleep stability and reduces sleep fragmentation. Zolpidem restores slow oscillation in young APP/PS1 (amyloid precursor protein/presenilin 1) mice. Zolpidem treatment reduces amyloid plaque burden and calcium overload in neurons. Zolpidem-treated mice show improved sleep-dependent memory consolidation. Sleep rhythm enhancement shows promise for Alzheimer's therapy.},
}

Animals
*Zolpidem/pharmacology
Mice
Disease Models, Animal
Mice, Transgenic
*Alzheimer Disease/drug therapy
*Sleep/drug effects
*Plaque, Amyloid/pathology/drug therapy
Electroencephalography
Amyloid beta-Protein Precursor/genetics
Brain/drug effects/metabolism
Presenilin-1/genetics
Male

@article {pmid41810373,
year = {2026},
author = {Vellone, D and Guan, DX and Goodarzi, Z and Forkert, ND and Smith, EE and Ismail, Z},
title = {Apathy in Mild Behavioural Impairment: Associations with Cortical Thickness and Grey Matter Volume.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.25.26347107},
pmid = {41810373},
abstract = {Mild Behavioural Impairment (MBI) is defined by later-life onset of persistent behavioural changes and is recognized as a risk marker for cognitive decline and dementia. Apathy, a core MBI domain characterized by diminished interest, initiative, and emotional reactivity, can emerge before dementia and is hypothesized to be associated with structural brain changes. While previous studies have explored Alzheimer disease (AD)-related neuroanatomical substrates of apathy in the dementia clinical stage, few have investigated these associations in cognitively normal (CN) or mild cognitive impairment (MCI) individuals with persistent apathy consistent with MBI. Thus, this study explores structural brain differences between individuals with MBI-apathy and those without neuropsychiatric symptoms (no-NPS). Participants (n = 446; mean age = 69.6 years; 79.8% CN; 62.8% female) were drawn from the National Alzheimer's Coordinating Center and categorized into MBI-apathy (n = 59) and no-NPS (n = 387) groups. Linear regressions were used to model associations between NPS group and regional brain measures, with adjustments for age, sex, years of education, apolipoprotein E4 carrier status, intracranial volume, and Mini-Mental State Examination score, with false discovery rate (FDR) correction for multiple comparisons. Primary outcomes included two predefined AD meta-regions-of-interest (ROIs): 1) thickness: a composite measure of mean cortical thickness across the entorhinal cortex, inferior temporal gyrus, middle temporal gyrus, inferior parietal lobule, fusiform gyrus, and precuneus; and 2) volume: a composite measure of mean cortical and subcortical grey matter volume across the hippocampus, entorhinal cortex, amygdala, middle temporal gyrus, inferior parietal lobule, and precuneus. Primary outcomes also included cortical thickness and grey matter volume among individual ROIs including the ventral striatum (VS), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), ventrolateral prefrontal cortex (vlPFC), and dorsolateral prefrontal cortex (dlPFC). MBI-apathy status was associated with significantly lower AD-meta-ROI cortical thickness (Z -score difference [95% CI]; FDR-corrected p -value, -0.43 [-0.73 - [-0.12]]; 0.025) and lower AD meta-ROI grey matter volume (-0.50 [-0.71 - [-0.30]]; <0.001). MBI-apathy was also associated with significantly lower dlPFC thickness (-0.40, [-0.70 - [-0.09]]; 0.02) and volume (-0.28 [-0.50- [-0.06]]; 0.026) and lower OFC volume (-0.32, [-0.57 - [-0.07]]; 0.026) compared to the no-NPS group. Within a non-dementia sample, MBI-apathy was more strongly associated with established AD-vulnerable regions than with regions that have been traditionally implicated in apathy in dementia. Results suggests that during CN and MCI stages, MBI-apathy may reflect early AD-related neurodegeneration, with conventional apathy-related structural changes becoming more prominent as disease progresses.},
}

@article {pmid41810132,
year = {2026},
author = {Parnetti, L and Gaetani, L},
title = {Anti-amyloid therapies as a stress test for the effectiveness and sustainability of health systems engaged against Alzheimer's disease.},
journal = {The Lancet regional health. Europe},
volume = {64},
number = {},
pages = {101631},
pmid = {41810132},
issn = {2666-7762},
}

@article {pmid41810027,
year = {2026},
author = {Wang, S and Hao, W},
title = {Unveiling Scaling Laws of Parameter Identifiability and Uncertainty Quantification in Data-Driven Biological Modeling.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {41810027},
issn = {2331-8422},
abstract = {Integrating high-dimensional biological data into data-driven mechanistic modeling requires rigorous practical identifiability to ensure interpretability and generalizability. However, coordinate identifiability analysis often suffers from numerical instabilities near singular local minimizers. We present a computational framework that uncovers fundamental scaling laws governing practical identifiability through asymptotic analysis. By synthesizing Fisher information with perturbed Hessian matrices, we establish a hierarchical approach to quantify coordinate identifiability and inform uncertainty quantification within non-identifiable subspaces across different orders. Supported by rigorous mathematical analysis and validated on synthetic and real-world data, our framework was applied to HIV-host dynamics and spatiotemporal amyloid-beta propagation. These applications demonstrate the framework's efficiency in elucidating critical mechanisms underlying HIV diagnostics and Alzheimer's disease progression. In the era of large-scale mechanistic digital twins, our framework provides the scaling laws for data-driven modeling in terms of both parameter identifiability and uncertainty, ensuring that data-driven inferences are grounded in verifiable biological reality.},
}

@article {pmid41810011,
year = {2026},
author = {Farombi, T and Ibanez, A and Akinyemi, O and Elugbadebo, O and Oyinlola, O and Ogunde, G and Migeot, J and Udeh-Momoh, C and Akinyemi, R},
title = {Evaluation of perception towards brain health in Nigeria: Results from a nationwide awareness survey.},
journal = {Journal of public health in Africa},
volume = {17},
number = {1},
pages = {1270},
pmid = {41810011},
issn = {2038-9922},
abstract = {BACKGROUND: Brain health involves the continuous functioning of mental, cognitive, motor and physical abilities driven by brain processes. Despite high levels of brain health risk in Nigeria, there is a lack of data on the public perception of brain health.

AIM: The authors investigated the perception of brain health and explored the interplay between demographic factors and brain health awareness.

SETTING: The research was carried out among the Nigerian population.

METHODS: A total of 570 participants responded to a cross-sectional survey conducted using Google Form link shared through WhatsApp and Facebook and convenience sampling between April 2023 and August 2023. Brain health perceptions were assessed across key domains. Statistical Package for Social Sciences version 29.0 was used for analysis. Bivariate correlations and logistic regression explored the relationships between socio-demographics and brain health perception.

RESULTS: Substance use was rated by 67% of participants as influencing factor for brain health. All life stages were considered important for brain care. Men were less likely than women to attribute family income, substance use and sleep as key influences. Remarkably, only 43.9%, 19.5% and 19.5% of participants agreed that an association exists between hypertension, diabetes and arthritis with brain health.

CONCLUSION: The study's findings suggest that there are notable gaps and gender differences in perceptions, underscoring the need for targeted health education. Addressing these gaps could improve the understanding of factors influencing brain health and support policy efforts in Nigeria.

CONTRIBUTION: This study provides unique insight into the gaps in the public perception of brain health in Nigeria, serving as a baseline study for future research.},
}

@article {pmid41809973,
year = {2026},
author = {Santoni, M and Mastio, A and Pistis, M and Sagheddu, C},
title = {The dopaminergic system in neurodevelopment: preclinical models of neurodevelopmental disorders and susceptibility to neurodegeneration.},
journal = {Frontiers in cellular neuroscience},
volume = {20},
number = {},
pages = {1782731},
pmid = {41809973},
issn = {1662-5102},
abstract = {The dopaminergic system plays a pivotal role in neurodevelopment, guiding the formation and refinement of neural circuits underlying salience attribution, cognition, reward and aversion. Its maturation extends from prenatal life through adolescence and may be influenced by genetic and environmental factors. Evidence from preclinical models suggests that perturbations during these sensitive windows may alter neurodevelopmental trajectories toward maladaptive outcomes, increasing vulnerability to neurodevelopmental disorders. This mini-review synthesizes findings from animal models to examine how physiological dopaminergic maturation might be shaped by genetic, as well as environmental, factors. We discussed maternal immune activation, prenatal cannabis exposure, and genetic models directly targeting dopaminergic function, all of which underscore the critical role of dopamine dysregulation in shaping neurodevelopmental outcomes. Beyond neurodevelopmental disorders, we extend this framework to newly emerging evidence concerning how early-life dopaminergic perturbations may influence dopamine system resilience and predispose individuals to accelerated cognitive decline and neurodegenerative disorders. Midbrain dopamine neurons exhibit intrinsic vulnerabilities that may render them especially sensitive to cumulative developmental and aging-related stressors and may serve as early predictors of disease. Finally, we discuss the therapeutic implications, emphasizing the limited mechanistic innovation in current pharmacological treatments and the growing need to target upstream or convergent developmental mechanisms in order to modify disease trajectories before overt dopaminergic dysfunction becomes established.},
}

@article {pmid41809690,
year = {2025},
author = {Noshin, K and Hou, B and Boland, MR and Wen, Z and Tong, B and Shen, L and Zhang, A},
title = {IRIS: Interpretable Risk Clustering Intelligence for Survival Analysis.},
journal = {Proceedings : ... IEEE International Conference on Big Data. IEEE International Conference on Big Data},
volume = {2025},
number = {},
pages = {1143-1152},
pmid = {41809690},
issn = {2639-1589},
abstract = {Survival analysis models have evolved significantly with deep learning approaches, yet often lack interpretability and meaningful risk stratification capabilities. We present Interpretable Risk Clustering Intelligence for Survival Analysis (IRIS), a novel framework that addresses the critical task of risk clustering while enhancing both input-level and model-body interpretability. Unlike traditional survival models that perform post-hoc risk clustering, IRIS learns to cluster patients into meaningful risk groups directly from data while providing transparent feature importance estimation through feature contribution functions. We validate IRIS on several benchmark datasets, a real-world Alzheimer's disease dataset, and an electronic health record dataset, showing superior performance in risk clustering and predictive reliability with only a modest decrease in time-to-event prediction accuracy compared to state-of-the-art methods. Our results show that IRIS successfully balances the trade-off between interpretability and prediction performance in risk-based survival analysis, offering clinicians actionable insights for treatment planning and resource allocation.},
}

@article {pmid41809632,
year = {2026},
author = {Mazurek, CY and Kaniuk, JK and Ahuja, CS},
title = {Mesenchymal stem cells and the central nervous system: historical perspectives and future directions.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1742864},
pmid = {41809632},
issn = {1662-5099},
abstract = {Mesenchymal stem cells (MSCs) have been studied as a potential therapy for a wide range of conditions for approximately 30 years. MSCs have shown promise in treating pathologies of or affecting the central nervous system (CNS), specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), traumatic brain injury (TBI), degenerative disc disease (DDD), and sepsis/meningitis. The therapeutic benefits of MSCs derive primarily from their arsenal of secreted factors that promote anti-inflammatory and pro-survival pathways while attenuating harmful immune responses, thus making them powerful immunomodulatory entities which are also capable of affecting a diverse range of cellular functions to promote endogenous mechanisms of repair. This review summarizes the current state of clinical trials research regarding pathologies of the CNS with a focus on historical progression and upcoming trials. We take a mechanistic approach to explain the therapeutic basis of MSCs and how this has informed clinical trials. We also mention the role of the MSC secretome and MSC exosomes in the treatment of CNS pathologies as well as their increasing use in clinical trials. Finally, we address the challenges inherent to the clinical translation and implementation of MSC therapies along with future directions of the field.},
}

@article {pmid41809502,
year = {2026},
author = {Stowe, AM and Kahn, B and Ballesteros, A and Cortez, M and Hynan, LS and Cantrell, V and Raman, I and Chen, G and Vidoni, ED and Binder, E and Burns, J and Keller, JN and Kerwin, DR and Hall, T and Yanev, P and Vongapatanasin, W and Zhu, DC and Scheel, N and Cullum, CM and Zhang, R and German, DC},
title = {Plasma p-tau217 and APOE genotype: Prodromal Alzheimer's disease staging.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70279},
pmid = {41809502},
issn = {2352-8729},
abstract = {INTRODUCTION: Plasma phosphorylated tau (p-tau)217 levels and apolipoprotein E (APOE) ε4 genotype are used for prodromal identification of individuals at high risk for dementia. We used baseline samples from cognitively normal subjects in the Risk Reduction for Alzheimer's Disease (rrAD) clinical trial (NCT02913664) to investigate the relationship between these two markers in older adults with additional vascular risk factors.

METHODS: We measured APOE genotype, plasma p-tau217, and standard neuroimaging metrics in 400 rrAD participants, aged 60 to 84 years, with sedentary lifestyle, hypertension, and hypercholesterolemia.

RESULTS: Plasma p-tau217 was 57% higher in subjects with at least one APOE ε4 allele, increased with age, was higher in males, and negatively correlated with brain volume measures by magnetic resonance imaging.

DISCUSSION: Plasma p-tau217 demonstrated elevation in the APOE ε4 genotype in cognitively normal older adults. These data also suggest that brain volume shrinkage in males is related to elevated p-tau217. APOE genotyping will be important for clinical practice using p-tau217 quantification.},
}

@article {pmid41809501,
year = {2026},
author = {Brenowitz, WD and Risacher, SL},
title = {Sensory changes in preclinical, prodromal, and clinical Alzheimer's disease and related dementias.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70298},
pmid = {41809501},
issn = {2352-8729},
}

@article {pmid41809433,
year = {2026},
author = {Wang, MA and Wu, H and Bonner-Jackson, A and Chen, Y and Tang, W and Feng, H and Zhang, L and Chen, C and Leverenz, JB and Pillai, JA},
title = {Early Behavioral and Cognitive Changes in Patients With Pathologically Confirmed Alzheimer Disease, Lewy Body Dementia, and Mixed Dementia.},
journal = {Neurology open access},
volume = {2},
number = {1},
pages = {},
pmid = {41809433},
issn = {2998-7601},
abstract = {BACKGROUND AND OBJECTIVES: Alzheimer's disease pathology (ADP) and Lewy body pathology (LBP) are traditionally associated with distinct cognitive profiles. However, growing evidence highlights the role of behavioral and psychological symptoms of dementia (BPSD) in shaping clinical presentations. The combined influence of cognitive and behavioral symptoms across neuropathologically confirmed ADP, LBP, and mixed AD-LBP has not been systematically examined. This study aimed to identify clinically meaningful subtypes by jointly analyzing cognitive performance and BPSD profiles in individuals with autopsy-confirmed dementia pathology.

METHODS: This retrospective longitudinal cohort study used data from the National Alzheimer Coordinating Center (NACC), collected across multiple U.S. Alzheimer's Disease Research Centers. Participants had a Clinical Dementia Rating (CDR) Global score ≤1 at baseline and autopsy-confirmed ADP, LBP, or mixed AD-LBP. Cognitive outcomes included standardized tests of memory, executive function, and language. BPSD were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q), which captures ten symptom domains: agitation, apathy, depression, delusions, disinhibition, auditory and visual hallucinations, irritability, personality change, and REM sleep behavior disorder. Cluster analysis was applied to identify subtypes based on combined cognitive and BPSD data.

RESULTS: The study included 1,028 participants (mean age at baseline 76.4 years; 47.6% female): 521 with ADP, 96 with LBP, and 411 with mixed AD-LBP. A three-cluster clinical subtype (CS) solution best fit the data. The most symptomatic group (CS-3) had the youngest age at first visit (mean 72.1 years), the highest BPSD burden, and the fastest cognitive and functional decline across ADP and AD-LBP groups. CS-1 and CS-2 exhibited milder early cognitive impairment and lower BPSD burden. Within ADP and AD-LBP, CS-2 showed slower progression than CS-1, fewer APOE ε4 carriers (41% vs. 58%), and better memory scores, despite reporting a higher frequency of agitation.

DISCUSSION: These findings reveal distinct clinical subtypes that cut across traditional pathological boundaries, emphasizing the need to incorporate both cognitive and behavioral features into early dementia characterization. This multidimensional approach can improve guide personalized prognosis and care planning and enhance clinical trial design by considering disease heterogeneity. The study supports integrated clinical profiling as important factor in robust evaluation of dementia outcomes.},
}

@article {pmid41809245,
year = {2026},
author = {Bertrand, F and Strauss, M and Leurquin-Sterk, G and Lesage, V and Vandenberghe, M and Fery, P and Maenhout, C and Bier, JC},
title = {When images come to life: a case series.},
journal = {BMJ neurology open},
volume = {8},
number = {1},
pages = {e001352},
pmid = {41809245},
issn = {2632-6140},
abstract = {BACKGROUND: Delusional misidentification syndromes (DMS) involve erroneous identification of people, objects or places. They have been described in several psychiatric and neurological diseases, particularly in cognitive disorders and dementia. We report an unusual form of DMS in patients with dementia: the belief that individuals depicted in photographs or static images are alive.

METHODS: In this retrospective analysis, four patients followed in our memory clinic between March 2009 and June 2025 were selected for having developed, during follow-up, the belief that individuals depicted in two-dimensional representations were alive, as reported by themselves or caregivers. A standardised neuropsychological battery assessed the main cognitive domains. Final diagnoses were established during multidisciplinary consensus meetings based on neuropsychological assessments, brain MRI, 18F-FDG-PET, DaT-scan results (when available) and cerebrospinal fluid (CSF) biomarkers. Clinical data are detailed in this study.

RESULTS: All four patients exhibited core delusions in the context of dementia, with heterogeneous severity, symptom duration and treatment response, but all showed marked emotional-behavioural involvement and functional decline. Neuroimaging demonstrated widespread frontoparietotemporal hypometabolism with consistent right-hemispheric involvement; two patients had predominant left-sided hypometabolism without clinical differences. CSF biomarkers indicated Alzheimer's pathology in all cases, and probable dementia with Lewy bodies was diagnosed in two patients based on core clinical features, including a positive DaT-scan in one of them.

CONCLUSIONS: We describe a previously unreported DMS variant-'animated picture syndrome'-characterised by the belief that individuals depicted in photographs or static images are alive, sometimes leading to behaviours such as reluctance to leave home or preparing food for them. In our series, this syndrome emerged in the context of neurodegenerative disease and coincided with cognitive and functional decline. Its recognition may help identify clinical deterioration and prompt appropriate aetiological work-up, caregiver education and therapeutic interventions. Further studies should clarify its prevalence, mechanisms and relationship with other DMS variants.},
}

@article {pmid41809238,
year = {2026},
author = {Lam, TK and Rhind, SG and Tenn, C and Nakashima, A and Shiu, MY and King, K and Caddy, N and Vallikanthan, J and Crouzat, M and Lester, L and Vartanian, O},
title = {One is not like the other: Examining the neural response to repetitive low-level blast exposure in experienced military personnel.},
journal = {Neuroimage. Reports},
volume = {6},
number = {1},
pages = {100335},
pmid = {41809238},
issn = {2666-9560},
abstract = {BACKGROUND: Military members often report concussion-like symptoms from repetitive low-level blast (LLB) exposure, defined as overpressure from outgoing munitions like rifles and explosive breaching. Typically, the early stages of concussion and other neurological conditions (e.g., Alzheimer's Disease) lead to hyperconnectivity which is a transient and adaptive brain response to strengthen and establish neural connections to restore brain function. Over time, however, chronic hyperconnectivity can contribute to neurodegeneration. To determine whether LLB exposure also exhibits this connectivity trajectory, this study investigated the neural signature of LLB at two time points: At the chronic stage extrapolated from the duration of an individual's occupational career, and following a recent and concentrated blast regimen.

METHODS: Forty-six military breachers and snipers underwent a resting state functional magnetic resonance imaging brain scan before and after a training course. Graph theory was used to study the whole-brain network, cross-validated by a principal components analysis (PCA) conducted post-hoc. The pre-course scan was analyzed separately to examine the neural effects of chronic LLB exposure. The pre- and post-course scans were compared to examine the neural effects of recent blast exposure. Military controls without occupational breaching and/or sniping experience underwent the same protocol.

RESULTS: At pre-course, breachers and snipers exhibited hyperconnectivity compared to controls. However, after undergoing a recent LLB regimen, only breachers showed hypoconnectivity post-course relative to pre-course compared to controls.

CONCLUSION: The mechanism of repeated LLB overpressure and its associated neural response to this exposure appear to be specific to this condition. Characterizing LLB exposure can help refine assessment and treatment.},
}

@article {pmid41809190,
year = {2026},
author = {Yang, Y and Huh, Y and Lee, K and Kwak, YT},
title = {Six-month randomized, double-blind trial of transcranial direct current stimulation in mild Alzheimer's dementia: domain-specific cognitive and neuropsychiatric signals.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1749559},
pmid = {41809190},
issn = {1664-2295},
abstract = {BACKGROUND: Prefrontal transcranial direct current stimulation (tDCS) is a low-risk candidate intervention for cognitive enhancement in Alzheimer's disease (AD), but trial results are heterogeneous and often short-term. We evaluated the 26-week efficacy, safety, and family-level impact of home-based prefrontal tDCS in mild AD.

METHODS: In this randomized, double-blind, sham-controlled trial, 120 patients with mild AD were allocated to active (n = 59) or sham (n = 61) tDCS. The intention-to-treat (ITT) population included 106 participants (53 vs. 53) with post-baseline data; 66 (32 vs. 34) comprised the per-protocol (PP) set. The primary outcome was change in global cognition on the Korean Mini-Mental State Examination (K-MMSE). Secondary and exploratory outcomes included domain-specific cognition [e.g., Korean Boston Naming Test (K-BNT)], neuropsychiatric symptoms [Korean Neuropsychiatric Inventory (K-NPI)], patient quality of life (QoL-AD), and caregiver-reported family quality of life [Family Quality of Life-Dementia (FQoL-D)]. Adverse events (AEs) were systematically monitored.

RESULTS: K-MMSE declined slightly in both groups over 26 weeks (active Δ -0.53, sham Δ -0.15), with no significant between-group difference (p = 0.402). Most cognitive domains showed small, non-significant changes. In contrast, confrontation naming on the K-BNT favored active tDCS: in ITT analyses, naming performance was stable with active stimulation (Δ +0.51) but worsened with sham (Δ -2.32; p = 0.022), with a similar pattern in the PP set. K-NPI findings were inconsistent across analytic sets. Notably, FQoL-D declined in the active arm but improved in the sham arm in both ITT (Δ -2.19 vs. +1.94; p = 0.043) and PP analyses. Overall AE rates were similar; stimulation-site reactions were common but mild, and serious AEs were rare and deemed unrelated to tDCS.

CONCLUSION: In mild AD, 26 weeks of home-based prefrontal tDCS did not improve global cognition vs. sham, although a modest benefit in confrontation naming was observed. The deterioration in caregiver-reported family quality of life highlights the need to weigh potential cognitive gains against family burden in long-term home-based neuromodulation.

CLINICAL TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0005834.},
}

@article {pmid41809103,
year = {2026},
author = {Yang, H and Zhang, S and Zhong, L},
title = {Association between the Naples Prognostic Score and cognitive function in older adults: validation in Alzheimer's disease and vascular dementia.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1761323},
pmid = {41809103},
issn = {2296-861X},
abstract = {BACKGROUND: Accumulating evidence indicates that systemic inflammation and metabolic dysregulation might contribute to cognitive impairment. The Naples Prognostic Score (NPS), a composite measure integrating albumin, total cholesterol (TC), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR), provides a succinct profile of systemic inflammatory-metabolic status. This study investigated the association between the NPS and cognitive impairment in elderly Americans.

METHODS: We analyzed data from 2,595 participants (age ≥60) in the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Cognitive function was evaluated using Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (CFDAST), and Digit Symbol Substitution Test (CFDDS). Cognitive impairment was defined as scoring in the lowest quartile. Multivariate logistic regression, linear trend analysis, and subgroup analysis were used to assess the association between NPS and cognitive impairment. Furthermore, the distribution of NPS across different dementia subtypes was validated in an independent clinical cohort comprising 189 clinically diagnosed patients.

RESULTS: After full adjustment, higher NPS scores were associated with an increased risk of cognitive impairment. A significant association was observed specifically with executive function assessed by CFDAST (OR = 2.03, 95% CI: 1.18-3.51). Significant dose-response relationships were found for both CFDAST and CFDDS (P for trend = 0.007 and 0.025, respectively). In the clinical cohort, NPS levels were similarly elevated in patients with Alzheimer's disease (AD) and vascular dementia (VaD) (mean 3.11 vs. 3.03, p = 0.432), suggesting that systemic inflammatory-metabolic dysregulation may constitute a common pathological mechanism across multiple subtypes of dementia.

CONCLUSION: Higher NPS scores are independently associated with executive dysfunction in older adults. Although this scoring system has limited specificity in differentiating dementia subtypes, it shows potential as a screening tool for identifying populations at high risk of executive dysfunction. This underscores the potential of interventions targeting underlying inflammatory and metabolic pathways as a transdiagnostic strategy. Nevertheless, the predictive utility of the NPS requires comprehensive validation through prospective studies.},
}

@article {pmid41808871,
year = {2026},
author = {Suswidiantoro, V and Tang, KS and Rahman, K and Ariestanti, DM and James, RJ and Yan, CC and Kato, M and Saputri, FC},
title = {Natural compounds as multitarget agents in Alzheimer's diseases: evidence from in vivo and in vitro models.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1766470},
pmid = {41808871},
issn = {1663-9812},
abstract = {INTRODUCTION: Alzheimer's disease (AD), the most common cause of dementia, is marked by a gradual decline in cognitive function driven by amyloid-β (Aβ) deposition, tau hyperphosphorylation, synaptic failure, neuroinflammatory responses, and mitochondrial dysfunction. Despite extensive research efforts, currently available pharmacological treatments provide only limited symptomatic relief and do not prevent disease progression. These shortcomings have fuelled growing interest in natural compounds, which possess pleiotropic biological properties and may more effectively target the multifaceted pathology of AD.

METHODS: This systematic review was performed in compliance with the PRISMA 2020 guidelines. Comprehensive literature searches were conducted across PubMed, Scopus, and ScienceDirect to identify preclinical and clinical studies examining the effects of natural compounds in in vitro and in vivo models relevant to AD. Eligible studies assessed phytochemicals, herbal formulations, marine-derived substances, or nutraceuticals and their impact on core AD-related pathological features.

RESULTS: A total of 41 studies fulfilled the inclusion criteria, including 25 in vivo and 16 in vitro investigations. Across these studies, natural compounds consistently exhibited neuroprotective effects via multiple mechanisms associated with AD pathogenesis. These included the reduction of oxidative stress and neuroinflammation, inhibition of apoptotic pathways, modulation of amyloidogenic processes, attenuation of Aβ aggregation, regulation of tau-associated signalling, and preservation of synaptic function and cognitive outcomes.

CONCLUSION: Overall, the available evidence suggests that natural compounds confer multitarget neuroprotective effects that directly engage with key pathological mechanisms underlying AD. Nonetheless, significant translational challenges remain, particularly with respect to bioavailability, compound standardisation, and clinical efficacy. Further robust, well-controlled clinical trials are essential to establish the therapeutic value of these agents as potential disease-modifying interventions for AD.},
}

@article {pmid41808725,
year = {2026},
author = {Narasimman, V and Devendran, D and Balasingam, P and Ravi, V and Vijayan, K},
title = {Neuroprotective potential of silver nanoparticles synthesized using Sargassum polycystum in a Zebrafish model of Alzheimer's disease.},
journal = {3 Biotech},
volume = {16},
number = {4},
pages = {121},
pmid = {41808725},
issn = {2190-572X},
abstract = {UNLABELLED: Silver nanoparticles were biosynthesized using an aqueous extract of the brown seaweed Sargassum polycystum and evaluated for their neuroprotective potential in an aluminium chloride (AlCl3)-induced zebrafish model of neurotoxicity. Physicochemical characterization confirmed stable, spherical nanoparticles with a surface plasmon resonance peak at 445 nm, nanoscale size distribution, and negative zeta potential, indicating good colloidal stability. The synthesized AgNPs exhibited moderate antioxidant activity in DPPH and ABTS assays. Embryo toxicity assessment demonstrated biocompatibility at lower concentrations, while higher doses produced concentration associated developmental toxicity. In adult zebrafish, AlCl3 exposure induced significant locomotor impairment, anxiety-like behaviour, and cognitive deficits. Co-treatment with AgNPs, particularly at 100 µg/L, significantly improved locomotor activity, reduced anxiety-associated behaviours, and restored learning and memory performance. Biochemical analyses showed a significant reduction in malondialdehyde levels and acetylcholinesterase activity in AgNP-treated groups, indicating Attenuation of oxidative stress and cholinergic dysfunction. Histopathological evaluation further confirmed preservation of neuronal architecture and reduced neurodegeneration following AgNP treatment. Based on the results indicate that S. polycystum derived silver nanoparticles provide concentration associated neuroprotection against aluminium chloride -induced neurotoxicity in zebrafish and May represent a promising green nanotherapeutic approach for neurodegenerative disorders.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-04716-z.},
}

@article {pmid41808605,
year = {2026},
author = {Biber, S and Culhane, JE and Prado, MG and Mathew, S and Burrola-Mendez, Y and West, II and Van Heiden, S and Phuong, J and Allimatti, S and Lane, LG and Moulder, KL and Hale, BK and Kuzma, A and Wang, LS and Gao, S and Lai, A and Natarajan, K and Wang, S and Morris, JC and Noble, JM and Mooney, SD and Kukull, W and Saykin, AJ and Stephens, KA},
title = {Integrating real-world data with gold-standard longitudinal clinical and genomic data to advance precision medicine for the Alzheimer's Disease Research Center Program and beyond: a proof-of-concept data platform.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71207},
doi = {10.1002/alz.71207},
pmid = {41808605},
issn = {1552-5279},
support = {U24 AG072122/AG/NIA NIH HHS/United States ; P30 AG062429/AG/NIA NIH HHS/United States ; //ADSP Phenotype Harmonization Consortium (ADSP-PHC): U24 AG074855, U01 AG068057, and R01 AG059716)/ ; U54HG003273//Human Genome Sequencing Center at Baylor College of Medicine/ ; U54HG003067//Broad Institute Genome Center/ ; U01AG057659//American Genome Center at the Uniformed Services University of the Health Sciences/ ; U54HG003079//Washington University Genome Institute/ ; //John P. Hussman Institute for Human Genomics (HIHG) Center for Genome Technology (CGT)/ ; U01AG057659//Sequencing for the ADSP Follow Up Study (FUS)/ ; U01AG062943//Sequencing for the ADSP Follow Up Study (FUS)/ ; U01AG032984//Alzheimer's Disease Genetic Consortium (ADGC)/ ; RC2AG036528//Alzheimer's Disease Genetic Consortium (ADGC)/ ; R01AG064614//Dissecting the Genomic Etiology of non-Mendelian Early-Onset Alzheimer Disease/ ; U01AG049508// NIA/ ; U01AG052411// NIA/ ; //Genentech, Inc/ ; U54AG052427//Genome Center for Alzheimer's Disease/ ; U24AG041689//The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS)/ ; U24AG021886//National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)/ ; },
mesh = {Humans ; *Precision Medicine/methods ; *Alzheimer Disease/genetics/therapy ; *Genomics ; *Electronic Health Records ; United States ; Longitudinal Studies ; Medicare ; Male ; Female ; Proof of Concept Study ; Aged ; National Institute on Aging (U.S.) ; },
abstract = {INTRODUCTION: Integrating real-world data (RWD) with clinical research datasets creates more complete, context-rich resources to drive discovery and enable precision medicine in Alzheimer's disease and related dementias. The National Alzheimer's Coordinating Center conducted a proof-of-concept (POC) project to link its longitudinal Uniform Data Set (UDS) with electronic health records (EHRs), Medicare claims, and genomic data.

METHODS: In partnership with three Alzheimer's Disease Research Centers (ADRCs), we developed scalable data pipelines and a governance framework to collect, harmonize, and securely share linked data through the National Institute on Aging's LINKAGE Program.

RESULTS: We linked UDS and EHR data for 2206 participants and added Medicare claims for 1522. Nearly 500 participants have 5 or more years of linked data, with genomic profiles available for 93%.

DISCUSSION: This POC demonstrates the feasibility of integrating clinical, genomic, and RWD across ADRCs, offering a scalable model for broader implementation.},
}

Humans
*Precision Medicine/methods
*Alzheimer Disease/genetics/therapy
*Genomics
*Electronic Health Records
United States
Longitudinal Studies
Medicare
Male
Female
Proof of Concept Study
Aged
National Institute on Aging (U.S.)

@article {pmid41808585,
year = {2026},
author = {Muñoz, P and Ali, HG and Demetriou, A and Latorre-Leal, M and Shimozawa, M and Delac, L and Troncea-Sandu, TF and Inzunza, J and Nilsson, P and Maioli, S and Nalvarte, I},
title = {Effects of gonadectomy on brain sex hormone levels and amyloid pathology in male and female App[NL-G-F] and App[NL-F] mice.},
journal = {Journal of neuroendocrinology},
volume = {38},
number = {3},
pages = {e70161},
doi = {10.1111/jne.70161},
pmid = {41808585},
issn = {1365-2826},
support = {2023-02366//Vetenskapsrådet/ ; R01AG065209/AG/NIA NIH HHS/United States ; AF-1031993//Alzheimerfonden/ ; DF-1031918//Demensfonden/ ; //Egyptian Cultural and Educational Bureau/ ; },
mesh = {Animals ; Male ; Female ; Mice ; Mice, Transgenic ; *Alzheimer Disease/metabolism/pathology ; *Brain/metabolism/pathology ; *Gonadal Steroid Hormones/metabolism ; Estrogens/metabolism ; Disease Models, Animal ; Amyloid beta-Protein Precursor/genetics ; *Testosterone/metabolism ; Ovariectomy ; *Castration ; Sex Characteristics ; Amyloid beta-Peptides/metabolism ; },
abstract = {More women than men are diagnosed with Alzheimer's disease (AD). Sex hormones have been ascribed neuroprotective properties, and their decline, particularly the reduction of estrogen during menopause, has been implicated in AD risk. In this study, we examined how loss of circulating sex hormones affects cognitive performance and amyloid pathology in two mouse models of AD, the aggressive App[NL-G-F] and the slower App[NL-F] models of brain amyloidosis. Bilateral gonadectomy was induced in both male and female App[NL-G-F] and App[NL-F] mice. Pathology was assessed using cognitive tests and histological evaluations of amyloid depositions and neuroinflammation. Serum and brain estrogen and testosterone levels were measured by ELISA, and the expression of key estrogenic signaling genes was evaluated using qPCR. We report that female gonadectomy had little impact on behavior or pathology in the App[NL-G-F] model, whereas male gonadectomy improved learning and reduced hippocampal amyloid depositions. In the App[NL-F] model, gonadectomy worsened amyloid pathology in both sexes. Hormone analysis revealed that significant levels of estrogen in females, but not testosterone in males, remain partly preserved in the brain after gonadectomy, and that low testosterone levels associate with increased insulin-like growth factor 1 (IGF-1) expression which may play a compensatory role in maintaining estrogenic signaling. Our study provides new insights into how the loss of circulating sex hormones influences brain sex hormone levels and AD pathology and contributes to a better understanding of the sex differences observed in this disease.},
}

Animals
Male
Female
Mice
Mice, Transgenic
*Alzheimer Disease/metabolism/pathology
*Brain/metabolism/pathology
*Gonadal Steroid Hormones/metabolism
Estrogens/metabolism
Disease Models, Animal
Amyloid beta-Protein Precursor/genetics
*Testosterone/metabolism
Ovariectomy
*Castration
Sex Characteristics
Amyloid beta-Peptides/metabolism

@article {pmid41808488,
year = {2026},
author = {Zhang, Y and Zhang, D and Xiao, H},
title = {Regulated neuronal death in Alzheimer's disease: Crosstalk and convergence of apoptosis, pyroptosis, senescence, and ferroptosis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430002},
doi = {10.1177/13872877261430002},
pmid = {41808488},
issn = {1875-8908},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and cognitive impairment. Despite its rapidly increasing global prevalence, effective disease-modifying therapies remain limited. Neuronal loss is a central pathological hallmark of AD, yet classical proteinopathy frameworks centered on amyloid-β (Aβ) deposition and tau hyperphosphorylation do not fully explain the extent and dynamics of neurodegeneration. Convergent upstream pressures-including Aβ/tau-associated proteotoxicity, mitochondrial dysfunction and oxidative stress, glucose hypometabolism/brain insulin resistance, and chronic neuroinflammation-lower the threshold for regulated neuronal death programs. Evidence from human postmortem brains and experimental AD models implicates multiple death modalities, including apoptosis, inflammasome-associated pyroptosis, cellular senescence with a senescence-associated secretory phenotype (SASP), and ferroptosis driven by iron-dependent lipid peroxidation. These signatures are often mixed and show region- and stage-dependent patterns, reflecting context- and model-specific drivers rather than mutually exclusive pathways. A crosstalk-and-convergence view highlights shared hubs-oxidative stress, mitochondrial failure, inflammasome/cytokine signaling, and SASP-mediated chronic inflammation-that connect these modalities through feed-forward loops, helping to explain the limited durability of single-pathway interventions. This review summarizes recent advances across these four pathways, discusses their mechanistic interplay, and outlines translational considerations (blood-brain barrier delivery, target specificity, and limited clinical evidence). We also highlight priorities for future work, including single-cell/spatial profiling, multi-omics integration, and biomarker-guided stratification to enable rational combination strategies.},
}

@article {pmid41808468,
year = {2026},
author = {Appiah, F and Simpong, DL and Marfo, E and Osei, GN and Antwi, MH and Manu, KS and Dogah, J and Bockarie, A},
title = {Association between lipid levels and dementia risk among older Ghanaian adults.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430772},
doi = {10.1177/13872877261430772},
pmid = {41808468},
issn = {1875-8908},
abstract = {BackgroundDementia is an escalating global public health concern, with Alzheimer's disease accounting for the largest proportion of cases. However, evidence on its association with lipid abnormalities remains limited in low- and middle-income countries, particularly in sub-Saharan AfricaObjectiveTo examine the association between lipid profile parameters and dementia risk among older adults in Ghana.MethodsA retrospective cross-sectional study was conducted using records from 16 individuals diagnosed with dementia and 28 age-matched controls. Lipid levels including total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, non-HDL cholesterol, and coronary risk index, were analyzed using descriptive statistics and binary logistic regression.ResultsDementia cases had higher median levels of total cholesterol (5.29 versus 4.69 mmol/L), triglycerides (1.20 versus 0.86 mmol/L), low-density lipoprotein (3.38 versus 2.75 mmol/L), non-HDL cholesterol (3.89 versus 3.23 mmol/L), and coronary risk index (5.18 versus 3.15) compared to controls. Elevated coronary risk was strongly associated with dementia (aOR = 13.87, p = 0.010), indicating a markedly increased likelihood of cognitive impairment among individuals with higher cardiovascular risk. However, none of the individual lipid levels remained significant after adjustment for hypertension and the potential confounding effects of each lipid parameter on the others.ConclusionsOverall cardiovascular risk, rather than isolated lipid markers, appears more relevant in dementia risk assessment among older Ghanaian adults. Early evaluation and management of coronary risk may play a critical role in dementia prevention.},
}

@article {pmid41808420,
year = {2026},
author = {Ren, D and Zhu, H and Zhang, T and Xiao, L and Xu, J and Li, R},
title = {Hypermethylation of FGF13 Reduces Microtubule Stability via Interaction With TUBB2A to Promote Mitochondrial Dysfunction in Alzheimer's Disease.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {6},
pages = {e71654},
doi = {10.1096/fj.202504152R},
pmid = {41808420},
issn = {1530-6860},
support = {2023JJ30862//Hunan Provincial Natural Science Foundation of China/ ; 2024JJ5544//Hunan Provincial Natural Science Foundation of China/ ; },
abstract = {Alzheimer's disease (AD) represents a primary contributor to cognitive deterioration in the elderly population. Mitochondrial dysfunction, which is closely associated with microtubule instability, contributes to AD progression. TUBB2A, a key microtubule protein, is essential for mitochondrial transport and neuronal function. This study investigates how DNA methylation of FGF13 affects mitochondrial function and its role in AD via the FGF13/TUBB2A axis. AD mouse models were established by injecting Aβ25-35 into the hippocampus, and dual-fluorescence staining was employed to quantify the expression levels of FGF13 and TUBB2A in different neural cell types in brain tissue. Western blotting assessed microtubule stability and mitochondrial function in the hippocampus. Nissl and TUNEL staining were used to detect neuronal survival and apoptosis, and transmission electron microscopy was used to observe the ultrastructure of mitochondria. Flow cytometry was employed to determine mitochondrial membrane potential in hippocampal tissue, and Methylation-Specific PCR was used to detect the methylation levels of FGF13. Co-immunoprecipitation experiments verified the interaction between FGF13 and TUBB2A. Mitochondrial dysfunction exists in the hippocampal tissue of AD mice. Overexpression of FGF13 alleviated mitochondrial ROS, enhanced microtubule stability, increased mitochondrial membrane potential, and reduced neuronal apoptosis, thereby improving symptoms. FGF13 was found to be methylated, and its methylation affected its direct binding with TUBB2A. Overexpression of FGF13's protective effects on neurons could be reversed by knocking down TUBB2A. The expression of FGF13 is reduced in AD mouse neurons, which is associated with its high methylation state. Overexpression of FGF13 improves microtubule stability and mitochondrial function in hippocampal neurons through interaction with TUBB2A, suggesting a potential therapeutic relevance in AD.},
}

@article {pmid41808410,
year = {2026},
author = {Scala, M and Sahu, RK and Severino, M and Traverso, M and Iacomino, M and Pedemonte, M and Santorelli, F and Tozza, S and Zara, F and Fiorillo, C and Chung, HL},
title = {ASAH2 deficiency affects sphingolipid homeostasis and neuromotor control, causing a progressive neurological disorder.},
journal = {HGG advances},
volume = {},
number = {},
pages = {100587},
doi = {10.1016/j.xhgg.2026.100587},
pmid = {41808410},
issn = {2666-2477},
abstract = {Sphingolipids are integral components of cell membranes and modulate cell survival, proliferation, and apoptosis. ASAH2 is a brain- and gut-enriched gene encoding the neutral N-acylsphingosine amidohydrolase 2, a poorly characterized member of the human ceramidase family. This enzyme plays a pivotal role in maintaining the sphingolipid homeostasis, which is crucial for neurogenesis and synaptic function in central and peripheral nervous system. In fact, a dysregulated sphingolipid metabolism is associated with progressive neurological conditions, including Alzheimer's disease and Parkinson's disease. Here, we report the identification of biallelic ASAH2 variants in an individual with a neurodevelopmental condition featuring cognitive impairment, neuropathy, ophthalmoplegia, and progressive cerebellar and extraocular muscles atrophy. Through exome sequencing, we identified very rare missense ASAH2 variants, predicted to be deleterious by in silico analyses. Muscle biopsy histopathologic evaluation revealed features suggestive of neuropathic damage. Lipidomic profiling revealed a hyper-accumulation of glucosylceramide in the subject's cells. Then, the functional investigation of the ASAH2 variants in Drosophila showed the production of an unstable protein and consistent loss-of-function neuromotor phenotypes. Our findings support ASAH2 as a candidate gene for a previously uncharacterized neurodevelopmental disorder with neuropathic features and progressive cerebellar atrophy, underscoring the important role of this ceramidase in human nervous system.},
}

@article {pmid41808245,
year = {2026},
author = {Gröger, R and Englert, AL and Lalia, M and de Weerd, L and Rovere, M and Kunze, L and Palumbo, G and Wind-Mark, K and Fixemer, S and Roemer-Cassiano, SN and Franzmeier, N and Höglinger, G and Zwergal, A and Tahirovic, S and Werner, RA and Brendel, M and Gnörich, J},
title = {Assessment of early-phase [[18]F]florbetaben images as a proxy for brain metabolism in mouse models of Alzheimer's disease.},
journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism},
volume = {},
number = {},
pages = {271678X261420082},
doi = {10.1177/0271678X261420082},
pmid = {41808245},
issn = {1559-7016},
abstract = {[[18]F]FDG-PET and β-amyloid-PET are established tools for assessing biomarker status in Alzheimer's disease. In this study, we evaluated the potential of early-phase [[18]F]florbetaben (FBB) PET as a functional proxy for [[18]F]FDG-PET in preclinical Alzheimer's disease models by examining regional perfusion and glucose metabolism in two transgenic mouse lines. Ninety-two APPPS1 (n = 17), APP[SAA] (n = 56), and age- and sex-matched wild-type mice (n = 19; 3-12 months, 40% female) underwent static [[18]F]FDG-PET (30-60 min p.i.) and dynamic [[18]F]FBB-PET (0-60 min p.i.). Standardized uptake values were derived for both [[18]F]FDG-PET and [[18]F]FBB-PET for the whole brain and 14 Ma-Benveniste-Mirrione atlas regions. We identified the 1-3 min p.i. time window as optimal, yielding the highest concordance with [[18]F]FDG (R = 0.53, p < 0.0001) across all regions. Both APPPS1 and APP[SAA] mice exhibited significant increases in perfusion (both p < 0.0001) and glucose metabolism (APPPS1: p = 0.0028; APP[SAA]: p < 0.0001) compared to wild-type controls. These findings demonstrate that early-phase [[18]F]FBB-PET not only mirrors [[18]F]FDG-PET-derived metabolic changes but also enables a single-scan assessment of β-amyloid pathology and brain function, thereby reducing the number of required scans and potentially the number of animals per study, and strengthening the translational value of preclinical PET research.},
}

@article {pmid41808156,
year = {2026},
author = {Cho, YS and Kim, SH and Ryu, SH and Chung, C and Lee, N and Kim, N and Jeong, M and Kim, Y and Gwak, J and Choi, SY and Saido, T and Jung, YK},
title = {Altered trafficking of Kv1-Kvβ2 leads to neuronal hyperexcitability and memory deficits in amyloid-β pathology.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00936-2},
pmid = {41808156},
issn = {1750-1326},
support = {RS-2025-00519823//Ministry of Science and ICT, South Korea/ ; },
}

@article {pmid41808104,
year = {2026},
author = {Lin, L and Pan, Z and Wei, Z and Jiang, X and Lai, Y and Chen, M and Lin, F},
title = {ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer's Disease via Epigenetic Reprogramming of the Asxl1/LXRα-H3K4me3 Axis.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03740-3},
pmid = {41808104},
issn = {1742-2094},
support = {No.2023Y9289//Fujian Provincial Science and Technology Innovation Joint Funding Project/ ; No.2025J01073//Fujian Provincial Science and Technology Innovation Joint Funding Project/ ; No.2022J01413//Fujian Provincial Science and Technology Innovation Joint Funding Project/ ; No.82401643//National Natural Science Foundation of China/ ; },
}

@article {pmid41808074,
year = {2026},
author = {Lu, H and Chen, S and Tang, Y and He, W and Xia, S and Wu, Y},
title = {Sex differences in the associations between illness representations and behavioral intentions to seek early Alzheimer's detection in Chinese older adults.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07288-y},
pmid = {41808074},
issn = {1471-2318},
support = {Y202353191//General Scientific Research Project of the Zhejiang Provincial Department of Education/ ; 82271482//National Natural Science Foundation of China/ ; 2023ZY1018//Department of Science and Technology of Zhejiang Province/ ; OJQDSP2022013//Oujiang Laboratory/ ; },
}

@article {pmid41807935,
year = {2026},
author = {Yuan, Y and Sheng, L and Chen, Z and Zhang, Y and Li, Q and Chen, J and Ding, K and Shi, L and Hu, Q and He, W},
title = {Design of a configurable SoC for Alzheimer's disease detection based on multimodal signals.},
journal = {BMC bioinformatics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12859-026-06410-6},
pmid = {41807935},
issn = {1471-2105},
support = {2023ZL659//Zhejiang Province Traditional Chinese Medicine Science and Technology Project/ ; 2025AS018, 2024AS020//Yinzhou District Scientific and Technological Project/ ; 2024Y04//Yinzhou District Scientific and Technological Project/ ; 2025C01063//Zhejiang Province Leading Geese Plan Project/ ; 62474100,62174121,62134002//National Natural Science Foundation of China/ ; XQ2022000005//Ningbo University and Ningbo Yongxin Microelectronics Technology Co., LTD. Digital Integrated Circuit Design Joint Laboratory/ ; YJD202305//Ningbo University Graduate Education Practice Base/ ; 2024T016//Science and Technology Innovation 2035 Major Project of Ningbo/ ; 2022Z203//Science and Technology Innovation 2025 Major Project of Ningbo/ ; },
}

@article {pmid41807843,
year = {2026},
author = {Sims, S and Sen, F and Korkmaz, F and Barak, O and Cheliadinova, U and Yuen, T and Zaidi, M and Kim, SM},
title = {FSH Signaling in Osteoporosis and Alzheimer's Disease.},
journal = {Current osteoporosis reports},
volume = {24},
number = {1},
pages = {},
pmid = {41807843},
issn = {1544-2241},
support = {R01 AG071870/AG/NIA NIH HHS/United States ; U19 AG060917/AG/NIA NIH HHS/United States ; R01 AG071870/AG/NIA NIH HHS/United States ; R01 AG074092/NH/NIH HHS/United States ; },
}

@article {pmid41807716,
year = {2026},
author = {Xue, M and Zheng, W and Li, F and Gao, L and Jia, X and Pang, S},
title = {HIF3A-mediated aberrant activation of TXNIP promotes Alzheimer's disease progression.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-43404-z},
pmid = {41807716},
issn = {2045-2322},
abstract = {Oxidative stress (OS) is a hallmark of Alzheimer's disease (AD), yet the cell type-specific mechanisms remain unclear. We analyzed a single-cell RNA sequencing (scRNA-seq) dataset to assess OS-related features in AD. OS scores were calculated using multiple algorithms, and differential expression, enrichment, protein-protein interaction (PPI) network, and machine learning (ML) approaches were applied to identify key genes. Validation was performed at both bulk and single-cell levels, and functional assays were conducted to elucidate molecular mechanisms. OS activity was significantly elevated in AD, with pronounced heterogeneity across cell types. Astrocytes exhibited the highest OS activity, and their proportion was markedly reduced in AD. We identified 54 OS-upregulated genes enriched in neurodevelopment and synaptic processes. Through integrative ML, HIF3A was pinpointed as a key OS-related gene, showing high expression in astrocytes and strong correlation with OS pathways. Mechanistically, HIF3A directly bound to the TXNIP promoter, upregulated TXNIP expression, and thereby enhanced mitochondrial ROS production, impaired energy metabolism, and exacerbated OS in astrocytes. Our findings reveal that astrocytic HIF3A mediates aberrant OS responses in AD via transcriptional upregulation of TXNIP, offering insights into potential therapeutic targets to mitigate oxidative damage in AD.},
}

@article {pmid41807703,
year = {2026},
author = {Guo, S and Jin, H and Sun, H and Huang, S and Chen, Y and Chang, Y and Zhang, Y and Ding, L and Chen, S and Fu, C and Yin, Y and Cheng, W},
title = {TDP-43 pathology triggers neuroinflammation and cognitive impairment by inducing microglial necroptosis.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41807703},
issn = {1757-4684},
support = {82472014//MOST | National Natural Science Foundation of China (NSFC)/ ; 24ZR1450000//STCSM | Natural Science Foundation of Shanghai Municipality ()/ ; 23ZR1441200//STCSM | Natural Science Foundation of Shanghai Municipality ()/ ; },
abstract = {Pathological TAR DNA-binding protein-43 (TDP-43) is a defining feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease (AD). However, the mechanism by which TDP-43 pathology disrupts microglial function and drives neuroinflammation remains unclear. In this study, we demonstrated that cytoplasmically mis-localized TDP-43 exacerbated neuroinflammation, induced cell death, and impaired phagocytic function in microglial cells, primarily through receptor interacting serine/threonine kinase 3 (RIPK3)-dependent necroptosis. Pharmacological inhibition of RIPK3 with GSK872 markedly attenuated these pathological effects in vitro. These findings were further corroborated in a murine model with cytoplasmic TDP-43 mis-localization, where GSK872 treatment remarkably alleviated neuroinflammation and restored cognitive deficits. Mechanistically, our findings indicate that the nuclear depletion of TDP-43, resulted from its cytoplasmic mis-localization, impairs its ability to transcriptionally repress the Ripk3 gene, subsequently leading to RIPK3 upregulation and activation of RIPK3-dependent necroptosis. Collectively, our findings establish RIPK3-dependent necroptosis as a critical driver of TDP-43 pathology-mediated neuroinflammation and identified necroptosis as a promising therapeutic target in TDP-43-associated neurodegenerative disorders.},
}

@article {pmid41807565,
year = {2026},
author = {Picard, M and Kempes, CP},
title = {From cancer to Alzheimer's: could a renewed focus on energy transform biomedicine?.},
journal = {Nature},
volume = {651},
number = {8105},
pages = {303-305},
pmid = {41807565},
issn = {1476-4687},
}

@article {pmid41807519,
year = {2026},
author = {Greig, EE and Resnick, SM and Ferrucci, L and Tian, Q},
title = {Plasma lipids connecting olfaction with cognition and physical function.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-43857-2},
pmid = {41807519},
issn = {2045-2322},
}

@article {pmid41807382,
year = {2026},
author = {Sun, X and Tang, Y and Wang, X and Pereira Curia, G and Sternke-Hoffmann, R and Mörman, C and Gerez, JA and Riek, R and Wei, G and Luo, J},
title = {Alzheimer's Aβ catalyzes Tau phase separation and aggregation via early nanocluster solubilization.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70083-1},
pmid = {41807382},
issn = {2041-1723},
support = {10002967//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)/ ; },
abstract = {Extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated Tau are the two main pathological hallmarks of Alzheimer's disease (AD). Although the co-occurrence and synergistic effects of Aβ and Tau are well established, the mechanisms underlying their interplay in a biomolecular condensate environment remain unclear. Here we show that Aβ40 does not undergo liquid-liquid phase separation (LLPS) but significantly enhances Tau phase separation and is recruited into Tau condensates. This recruitment alters condensate physicochemical properties, accelerates liquid-to-solid maturation, promotes Tau amyloid fibril formation, and increases Tau-mediated cytotoxicity. Notably, prior to condensate formation, Aβ40 transiently solubilizes Tau nanoclusters into smaller species. Simulations further indicate that early interactions are non-specific and mediated by Tau repeat domains, ultimately promoting pathogenic aggregation. These findings support a model wherein Aβ act as a catalyst for Tau condensation and fibrillation towards pathological aggregates by solubilizing Tau nanoclusters during early phase interactions.},
}

@article {pmid41807336,
year = {2026},
author = {Shah, AS and Peterson, HE and Chakkalakal, R and Dusetzina, S and Fabius, C and Graves, J and Kim, J and Mumma, M and Lipworth, L and Stevenson, DG and Keohane, LM},
title = {Diabetes, Dementia, and Disruptions in Health Care Use in 2020 for Low-Income Medicare Beneficiaries.},
journal = {The Journal of ambulatory care management},
volume = {49},
number = {2},
pages = {E82-E95},
pmid = {41807336},
issn = {1550-3267},
mesh = {Humans ; United States/epidemiology ; Aged ; *Medicare/statistics & numerical data ; *Dementia/therapy/epidemiology ; Female ; Male ; *Poverty/statistics & numerical data ; *Diabetes Mellitus/therapy/epidemiology ; Aged, 80 and over ; Medicaid/statistics & numerical data ; *Patient Acceptance of Health Care/statistics & numerical data ; Nursing Homes/statistics & numerical data ; Home Care Services/statistics & numerical data ; },
abstract = {BACKGROUND: Despite widespread interruptions to health care in 2020, little evidence demonstrates how populations at highest risk for poor outcomes fared across a comprehensive scope of services.

METHODS: Among a predominantly low-income population of individuals ages 65 and older with diabetes (n = 4,187), we measured health care service use in Medicare and Medicaid claims data from 2018 to 2020. Stratified analyses included individuals with Alzheimer disease and related dementias (ADRD, n = 1,025), individuals who used Medicaid-funded home- and community-based services (HCBS, n = 264), and long-term nursing home services (n = 365).

RESULTS: Relative to 2018-2019, adjusted quarterly rates of evaluation and management visits dropped by 26% (95% confidence interval [CI]: 23%-28%) in Q2 2020 and remained 7% lower (95% CI: 4%-10%) in Q4 2020. Persistent declines occurred for inpatient discharges and emergency room visits (relative risk Q4 2020 vs. 2018-2019: 0.87 [95% CI: 0.76-0.99] and 0.77 [95% CI: 0.69-0.87], respectively). Insulin fills declined in later 2020 (relative risk Q4 2020 vs. 2018-2019: 0.87 [95% CI: 0.79-0.95]) while annual wellness visits rebounded (relative risk Q4 2020 vs. 2018-2019: 1.19 [95% CI: 1.06-1.34]). Individuals who used Medicaid-funded HCBS or long-term nursing home services before the pandemic had large declines in evaluation and management visits (relative risk Q4 2020 vs. 2018-2019: 0.80 [95% CI: 0.69-0.93] and 0.63 [95% CI: 0.43-0.94], respectively). Nursing home residents also had notable declines in insulin fills (relative risk Q4 2020 vs. 2018-2019: 0.73, 95% CI: 0.55-0.96). Individuals with ADRD had increased skilled nursing facility admissions (relative ratio Q3 2020 vs. 2018-2019 1.60, 95% CI: 1.21-2.13). Telehealth usage in 2020 did not differ based on ADRD diagnosis.

CONCLUSIONS: Extended disruptions in routine care highlight opportunities to improve support for older adults with diabetes.},
}

Humans
United States/epidemiology
Aged
*Medicare/statistics & numerical data
*Dementia/therapy/epidemiology
Female
Male
*Poverty/statistics & numerical data
*Diabetes Mellitus/therapy/epidemiology
Aged, 80 and over
Medicaid/statistics & numerical data
*Patient Acceptance of Health Care/statistics & numerical data
Nursing Homes/statistics & numerical data
Home Care Services/statistics & numerical data

@article {pmid41803833,
year = {2026},
author = {Feng, X and Liu, J and Liang, Z and Du, X and Zhao, L and Xie, N and Chen, C and Ding, L and Xia, X and Zheng, JC and Liu, J},
title = {Transcranial magnetic stimulation mitigates perioperative neurocognitive disorders by regulating the function of the glymphatic system.},
journal = {Cell communication and signaling : CCS},
volume = {24},
number = {1},
pages = {},
pmid = {41803833},
issn = {1478-811X},
support = {Nos. 82171194 and 82371204//the National Natural Science Foundation of China/ ; },
abstract = {UNLABELLED: The incidence of perioperative neurocognitive disorders (PND) increase with age, especially within those countries facing great challenge of aging population. However, the mechanism of PND remains elusive, and the lack of precautions has resulted in extended recovery among the elderly. Transcranial magnetic stimulation (TMS) has shown promising therapeutic potential in many neurological disorders such as depression and Alzheimer’s disease. This study aimed to explore the therapeutic potential of TMS on PND mouse model and aged patients. PND mice model were established through exploratory laparotomy on aged mice. We performed Y maze test and novel object recognition test to evaluate the cognitive function after TMS treatment. Intracisternal injection and immunofluorescence staining were conducted to assess the glymphatic system function. We used ELISA, immunofluorescence staining, Western-blotting and TUNEL assay to detect neuroinflammation and neuronal loss. We examined the therapeutic effect of TMS on patients in a clinical trial. PND mice showed improved cognitive functions after TMS treatment. TMS abrogated glymphatic system dysfunction and aquaporin-4 (AQP4) translocation, the key pathological changes that lead to cognitive decline, in PND mice. Moreover, TMS alleviated neuroinflammation and apoptosis in PND mice. We further found that inhibition of glymphatic system function blocked the ameliorative effects of TMS on postoperative cognitive function, neuroinflammation, and neuronal damage. Patients who received TMS showed improved memory function 7 days after surgery and obtained better Abbreviated Mental Test Score 30 days post-operation. Our study indicates the great therapeutic potentials of TMS in anesthesia- and surgery-induced cognitive impairment and pathological changes. Trial registration ChiCTR2200057080.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-026-02751-0.},
}

@article {pmid41680442,
year = {2026},
author = {Alqahtani, BA and Alhwoaimel, NA and Alshehri, MM and Alhowimel, AS and Alqahtany, MA and Alenazi, AM},
title = {Association of frailty and disability in community dwelling older adults: a cross sectional study.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41680442},
issn = {2045-2322},
abstract = {Frailty is one of the independent predictors of disability. There is a large shift in the Kingdom of Saudi Arabia toward improving health care system due to the increasing older adult population. Limited research has explained the relationship between frailty status and disability in Saudi older adults. Therefore, the aim of the current study was to investigate the relationship between physical frailty and disability using a cross-sectional design study. A total of 324 participants aged 50 years or older were recruited in the study; participants diagnosed with dementia, Alzheimer’s, or severe cognitive or physical impairment were excluded from the study. All participants underwent a physical examination procedure and completed structured questionnaires. Frailty status was determined using the FRAIL scale. Disability was categorized using the Activities of Daily Living scale. Samples were categorized based on frailty status (Frail, Pre-frail, and No-Frail) using the FRAIL scale. The sample’s mean age was 65.7 years, with females (71.7%) having a higher prevalence of disability than males (28.4%). Participants with two or more chronic conditions had a higher prevalence of disability (62.4%). The fully adjusted model shows that pre-frail (OR: 2.62; 95% CI [1.44, 4.97], p = 0.002) and frail (OR: 4.05; 95% CI [1.69, 9.65], p = 0.002) groups were significantly associated with having disability compared to robust group after adjustments for age, sex, BMI, and number of chronic conditions. This study provided a foundation for disability projects in Saudi Arabia to promote the understanding of the underlying mechanisms of the relationship between frailty and disability for the Saudi community.},
}

@article {pmid41653279,
year = {2026},
author = {Gayor, C and Scheiber, C and Janier, M and Craciun, D and Dautricourt, S and Desestret, V and Garnier-Crussard, A and Flaus, A},
title = {Simultaneous perfusion and dopaminergic imaging using dual-isotope CZT SPECT/CT in dementia with Lewy bodies.},
journal = {EJNMMI research},
volume = {16},
number = {1},
pages = {},
pmid = {41653279},
issn = {2191-219X},
abstract = {BACKGROUND: Current diagnostic criteria for dementia with Lewy bodies (DLB) include indicative and supportive biomarkers, some of which are typically assessed separately using dopamine transporter or perfusion imaging. Cadmium-zinc-telluride (CZT) Single Photon Emission Computed Tomography (SPECT) cameras improve simultaneous dual isotope acquisition using [[99m]Tc]-hexamethylpropyleneamine oxime ([[99m]Tc]TcHMPAO) (perfusion) and N-(3-Fluoropropyl)-2β-carbomethoxy-3β-(4-[[123]I]iodophenyl)nortropane ([[123]I]FP-CIT; dopamine transporter), allowing the assessment of one indicative and two supportive biomarkers in a single session. This study aimed to describe the results of dual-isotope brain SPECT imaging in a cohort of patients clinically diagnosed with DLB and to compare clinical characteristics, cognition, structural atrophy, and Alzheimer’s disease (AD) biomarkers, between imaging outcomes.

RESULTS: This retrospective single-center study included a total of 56 consecutive patients (mean ± standard deviation age 80.4 ± 7.8 years; 34% females) referred from an expert memory center finally diagnosed as DLB and who underwent a dual-isotope brain SPECT. Based on core clinical features from Mc Keith et al. revised diagnostic criteria, 40 patients (71%) were classified as probable DLB and 16 (29%) as possible DLB. Reduced dopamine transporter uptake (indicative biomarker) was observed in 84% of patients, while cerebral hypoperfusion was found in 100%. Supportive biomarkers such as cingulate island sign and occipital hypoperfusion were present in 29% and 55%, respectively. All 9 patients with normal dopamine transporter imaging had cerebral hypoperfusion and 3 of them presented supportive biomarkers of DLB. No significant association was found between imaging biomarker results and global cognition score, each core clinical features individually, medial temporal lobe atrophy, or CSF biomarkers for AD.

CONCLUSION: Dual-isotope brain SPECT using CZT frequently identifies dopamine transporter abnormalities in patients with DLB, always in conjunction with perfusion abnormalities. Patients with normal dopamine transporter imaging always present perfusion abnormalities. This imaging approach provides a more comprehensive assessment of indicative and supportive biomarkers in DLB, without increasing scan duration, potentially enhancing diagnostic confidence in clinical practice, particularly in challenging cases.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-026-01386-z.},
}

@article {pmid41645245,
year = {2026},
author = {Zhao, H and Liu, Y and Chen, X},
title = {The immunoproteasome as a neuroimmune hub in the central nervous system: from proteostasis stress to inflammatory pathology.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41645245},
issn = {1742-2094},
support = {81771250//National Natural Science Foundation of China/ ; 2023Y9286//Joint Funds for the innovation of science and Technology, Fujian province/ ; 2024J011004//Fujian Provincial Natural Science Foundation/ ; },
abstract = {The immunoproteasome (IP) is a stress-inducible specialization of the ubiquitin-proteasome system that integrates immune activation with cellular homeostasis in the central nervous system (CNS). Incorporation of the inducible β1i, β2i, and β5i subunits enhances proteolytic capacity under inflammatory, oxidative, and metabolic stress, thereby supporting redox balance, mitochondrial integrity, and proteostasis. IP expression is highly dynamic and cell type-specific, varying across astrocytes, microglia, endothelial cells, and neurons in response to local microenvironmental cues. Functionally, IP activation exhibits a dual nature: transient induction facilitates the clearance of damaged proteins and fine-tunes inflammatory signaling, whereas sustained or dysregulated activation reinforces NF-κB- and STAT-dependent inflammatory programs, disrupts proteostatic equilibrium, and increases neuronal and vascular vulnerability. Across neurological disorders, the IP acts as a context-dependent regulator, shaping post-ischemic inflammation and blood-brain barrier (BBB) integrity, contributing to maladaptive responses in Alzheimer’s and Parkinson’s disease, and amplifying immune-mediated injury in multiple sclerosis, neuromyelitis optica spectrum disorder, epilepsy, and infectious encephalitis. Elucidating the spatiotemporal regulation of the IP and its therapeutic selectivity may enable precision immunomodulatory strategies for CNS diseases.},
}

@article {pmid41807023,
year = {2026},
author = {Park, J and Kwon, MJ and Jo, S and Kim, JS and Kim, HI and Kim, Y and Han, JW and Kim, KW},
title = {Free Water Elevation in Alzheimer's Disease: Influence of Amyloid-Beta Deposition Beyond Brain Cell Loss.},
journal = {Journal of Korean medical science},
volume = {41},
number = {9},
pages = {e82},
doi = {10.3346/jkms.2026.41.e82},
pmid = {41807023},
issn = {1598-6357},
support = {HI09C1379 [A092077]/MOHW/Ministry of Health & Welfare/Korea ; RS-2020-KH095941//Korea Health Industry Development Institute/Republic of Korea ; RS-2020-KH095941/KDRC/Korea Dementia Research Center/Korea ; },
abstract = {BACKGROUND: To investigate whether amyloid-beta (Aβ) deposition in Alzheimer's disease (AD) increases free water (FW) before cell loss, we examined regional Aβ levels, volume, and FW of the posterior cingulate cortex (PCC) and medial and inferior temporal cortex (MITC) across AD stages.

METHODS: Aβ, volume, and FW in PCC and MITC were compared between normal cognition (NC), preclinical AD, prodromal AD, and dementia due to Alzheimer's disease (DEMAD) groups. Multiple linear regression was used to analyze the effect of Aβ and volume on FW.

RESULTS: Continuous increases were observed in the regional standardized uptake value ratio of ¹⁸F-Florbetaben (SUVR) and regional volume loss in all regions of interest. Also, there was a consistent rise in the MITC FW. However, in PCC volume, only DEMAD showed a significant decrease. In the context of multiple linear regression, the study found that both SUVR and volume were significant predictors of FW in the MITC. However, in PCC, only SUVR was able to predict FW without considering volume.

CONCLUSION: This study demonstrated that after Aβ deposition in AD, an increase in FW can occur not only due to brain cell loss but also through other Aβ-induced mechanisms, even in cases where brain cell loss has not yet occurred.},
}

@article {pmid41806661,
year = {2026},
author = {Raffoul, R and Lopez, JA and Vachon, A and Laurent, B and Plourde, M},
title = {Short-term docosahexaenoic acid rich diet prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice.},
journal = {Prostaglandins, leukotrienes, and essential fatty acids},
volume = {209},
number = {},
pages = {102730},
doi = {10.1016/j.plefa.2026.102730},
pmid = {41806661},
issn = {1532-2823},
abstract = {BACKGROUND: Metabolism of docosahexaenoic acid (DHA), an omega-3 (Ω3) fatty acid (FA), differs between carriers of the epsilon 4 allele of the apolipoprotein E (APOE4)-the main genetic risk factor for late-onset Alzheimer's disease-and APOE3 carriers. Dietary DHA has been shown to prevent cognitive decline in APOE4 carriers. However, whether DHA must be consumed the whole life is unclear. We hypothesized that a DHA intake started later in life and for a shorter duration prevents cognitive decline in APOE4 mice.

OBJECTIVE: To investigate three dietary durations of DHA on the prevention of cognitive decline in APOE4 mice.

METHODS: Mice knock-in for the human APOE3 (control, n = 84; 34 males/50 females) or APOE4 (n = 84; 39 males/45 females) allele were fed either a DHA-free control diet for 8 months or a diet rich in calcium salt DHA (0.5 g DHA/100 g diet) for 2, 4 or 8 months. Recognition memory was assessed using the novel object recognition test. DHA was quantified using gas chromatography.

RESULTS: APOE4 mice fed the control diet did not recognize the novel object as the APOE3 mice did suggesting cognitive decline in APOE4 mice. However, a DHA-Ca rich diet for 2 and 4 months prevented cognitive deficits in males (2M-P = 0.0414, 4M-P = 0.0073) and females (2M-P < 0.0001). 2-months DHA-Ca rich diet was associated with 18-25% higher cortical relative percentage of DHA in females and males compared to the control diet (Females-P = 0.0031; Males-P = 0.0010).

CONCLUSION: In APOE4 mice, it is not necessary to consume DHA-calcium salt throughout life to prevent cognitive decline.},
}

@article {pmid41806548,
year = {2026},
author = {Acharya, M and Deo, RC and Barua, PD and Devi, A and Tao, X},
title = {Graph empirical mode decomposition and multiscale feature extraction for EEG-based classification of Alzheimer's disease and frontotemporal dementia.},
journal = {Computer methods and programs in biomedicine},
volume = {279},
number = {},
pages = {109302},
doi = {10.1016/j.cmpb.2026.109302},
pmid = {41806548},
issn = {1872-7565},
abstract = {BACKGROUND AND OBJECTIVE: Early and correct classification of neurodegenerative diseases like Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) is one of the most important challenges in clinical neurology. In this paper, we present a novel electroencephalogram (EEG)-based approach that integrates a rich set of multiresolution features to improve the performance of automatic classification.

METHOD: Our approach fuses the Graph Fourier Transform (GFT), Graph Wavelet Transform (GWT), Discrete Wavelet Transform (DWT), and a newly developed Graph Empirical Mode Decomposition (GEMD) technique to primarily boost the performance of the proposed model. This also retained the complementary spatial, spectral, and temporal information carried by the EEG signals, which are significant for the differentiation of AD, FTD, and HC subjects. The EEG recordings were segmented into fixed lengths with non-overlapping windows of four durations: 1000, 5000, 10,000, and 20,000 samples. Energy and entropy features were obtained for each segment, both individually within domains and combined into a single 388-dimensional feature vector. The features were then normalized and fed into various machine learning (ML) models, including support vector machines (SVMs), k-nearest neighbors (kNNs), decision trees (DTs), random forests (RFs), and an ensemble learning model with the AdaBoost capability.

RESULTS: The proposed model was tested using accuracy, precision, recall, specificity, and F1-scores, with results showing that the ensemble model was better than the other benchmark models in every classification task. That is, in this binary classification problem, an accuracy of 98.84% for AD vs. HC, 98.67% for AD vs. FTD, and 98.94% for FTD vs. HC was obtained.

CONCLUSION: In the multiclass task (AD, FTD, HC), the method reached 96.68% accuracy, demonstrating the efficacy of the proposed method for the identification of Alzheimer's disease and frontotemporal dementia. Compared to previous research using the same dataset, our approach has demonstrated improved performance, validating the effectiveness of graph-based multiresolution feature fusion for dementia classification using EEG signals.},
}

@article {pmid41806384,
year = {2026},
author = {Garcia, D and Rai Sharma, SR and Saito, N and Beckett, L and Sevilla, LNC and Vasquez, R and DeCarli, CS and Gutman, D and Vizcarra, J and Coughlin, DG and Teich, AF and Garcia, L and Mungas, DM and Chuah, CN and Dugger, BN},
title = {Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease.},
journal = {Journal of neuropathology and experimental neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnen/nlaf152},
pmid = {41806384},
issn = {1554-6578},
support = {R01AG062517, P30AG072972, P30AG062429, P50AG008702, P30AG066462, and U24NS133949//National Institute on Aging (NIA) of the National Institutes of Health (NIH)/ ; },
abstract = {Machine learning enables scalable quantification of neuropathology, offering deeper phenotyping of Alzheimer's disease (AD). In this validation study, we quantified amyloid-beta (Aβ) deposits, evaluating multiple brain regions across institutions, and evaluated associations with clinical, demographic, and genetic factors in persons pathologically diagnosed with AD. All linear models were adjusted for sex, age of death, ethnicity, and center. We analyzed densities (#/mm2) of cored plaques, diffuse plaques, and cerebral amyloid angiopathy (CAA) in 273 individuals from 3 Alzheimer's Disease Research Centers. Formalin-fixed paraffin-embedded sections of frontal, temporal, and parietal cortices were immunostained and digitized, generating 799 whole-slide images (WSIs). Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P < .001); the temporal cortex had the highest diffuse plaque (P < .001); CAA showed no regional differences. Wilcoxon rank-sum test, and covariates adjusted linear models showed ApoE ε4- status was associated with higher cored plaque densities in the temporal lobe (P = .04). ApoE ε4+ status was associated with diffuse plaques in the temporal lobe (P = .001), and CAA in the frontal lobe (P = .004). These findings provide further validation and provide exploratory associations advancing deeper phenotyping of AD.},
}

@article {pmid41806367,
year = {2026},
author = {Levinson, AJ and Ayers, S and Clark, S and Woodburn, R and Schneeberg, A and Hadid, D and Kates, N and Strudwick, G and Grad, R and Papaioannou, A and Dobbins, M and Siu, H and Duarte, D and Saperson, K and Marr, S and Oliver, D and Neil-Sztramko, S},
title = {Effects of Internet-Based Dementia Risk Reduction Education on Risk and Protective Factor Knowledge, Intentions, and Health Behaviors: Randomized Controlled Trial.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e79405},
doi = {10.2196/79405},
pmid = {41806367},
issn = {1438-8871},
abstract = {BACKGROUND: Dementia prevention through the reduction of modifiable risk factors is gaining attention as a public health strategy. However, public knowledge of dementia risk and protective factors remains low. Web-based education offers a potential solution to raise awareness and promote risk-reduction behaviors.

OBJECTIVE: This randomized controlled trial evaluated the effectiveness of DementiaRisk.ca, an internet-based multimedia educational intervention, in increasing knowledge of dementia risk factors, intentions to engage in risk reduction behaviors, and changes in health behaviors.

METHODS: A 2-arm randomized controlled trial was conducted with 510 participants (265 in the intervention group and 245 in the control group). Participants were randomized to receive either the e-learning about dementia risk and promoting brain health, which included a multimedia lesson and microlearning emails, or a control intervention focused on mild cognitive impairment. Outcomes included knowledge of dementia risk factors, intentions to engage in risk reduction, and health behaviors, measured at baseline (T1), 4 weeks (T2), and 2 months postintervention (T3). Outcomes were analyzed using linear mixed effects models with fixed effects for group, time, and their interaction, and a random intercept for participants.

RESULTS: Of the 510 randomized participants, 405 (79.4%) completed all intervention components. Participants were predominantly female (n=309, 60.6%) and aged 55 years or older (n=284, 55.7%). Baseline mean dementia knowledge scores were 17.0 (SD 5.5) in the intervention group and 17.4 (SD 6.0) in the control group. At T2, scores increased to 25.8 (SD 4.5) and 23.6 (SD 5.1), respectively, yielding a between-group difference of 2.2 points (95% CI 1.2-3.2; P<.001), which was sustained at T3. Both groups showed significant improvements in knowledge, intentions, and health behaviors over time, with larger knowledge gains in the intervention group and particularly among participants with lower educational attainment. Intentions to engage in dementia risk reduction improved in both groups at T2 (intervention: +1.0, 95% CI 0.2-1.8; control: +1.4, 95% CI 0.5-2.3), with no significant between-group difference. Self-reported physical activity increased from 31.7 (SD 25.0) to 38.6 (SD 27.5) in the intervention group and from 29.9 (SD 23.5) to 32.5 (SD 26.6) in the control group, with a between-group difference of 5.4 points at T2 (95% CI 0.3-10.5; P=.04). No significant between-group differences were observed for diet, alcohol use, or other health behaviors. Qualitative findings indicated that participants valued the intervention for improving awareness of dementia risk factors, motivating proactive lifestyle changes, and enhancing confidence in applying prevention information.

CONCLUSIONS: This internet-based dementia risk reduction e-learning program improved dementia-related knowledge and increased self-reported physical activity, particularly among participants with lower educational attainment. Effects on other health behaviors were limited. These findings support the use of well-designed e-learning as a scalable public health strategy to strengthen dementia risk reduction literacy and encourage selected healthy behaviors.},
}

@article {pmid41806359,
year = {2026},
author = {Jiang, Z and Qin, Y and Luo, B and Bai, F and Liu, J and Ma, L and He, S and Chen, R and Wang, Y and Liu, S and Sun, Y and Chen, Y and Zhang, S and Liang, J and Liao, F and Wei, H and Wei, J and Wang, L and Xu, H and Wu, Z and Chen, G and Lei, W},
title = {A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair in Alzheimer's Disease-Like Non-Human Primate Model.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e20239},
doi = {10.1002/advs.202520239},
pmid = {41806359},
issn = {2198-3844},
support = {32571169//National Natural Science Foundation of China/ ; 202206060002//Guangzhou Municipal Science and Technology Program key projects/ ; 2021ZT09Y552//Guangdong Innovative and Entrepreneurial Research Team Program/ ; 2026A1515010137//Guangdong Basic and Applied Basic Research Foundation/ ; },
abstract = {There is a pressing demand for neuroregenerative treatment for Alzheimer's disease (AD). Recently, a NeuroD1-mediated neuroregeneration strategy has been proposed, yet its efficacy remains untested in non-human primate (NHP) AD models closely reflecting human pathology. This study evaluates the therapeutic potential of NeuroD1 AAV-based gene therapy in an NHP AD model with hippocampal hTau overexpression, utilizing immunostaining, fluorescence/confocal imaging, MRI and FDG PET scans, Simoa CSF biomarker analysis, behavioral tests, and bulk RNA sequencing. NeuroD1 AAV-based gene therapy prevents neuronal damage and degeneration, inhibits hippocampal atrophy, and reduces neuroinflammation in NHP AD models. It also repairs vascular and BBB damage, restores CSF AD biomarker levels, improves hippocampal glucose metabolism, and enhances spatial working memory. Transcriptome analysis further reveals upregulated neuronal function and synaptic transmission, along with downregulated neuroinflammation and apoptosis. Collectively, our findings demonstrate that NeuroD1 AAV-based gene therapy repairs and restores brain structure and function in NHP AD models, highlighting its therapeutic potential.},
}

@article {pmid41806350,
year = {2026},
author = {Yu, Y and Ma, Z and Li, T and Xiao, W and Li, Z},
title = {Neuronal Extracellular Vesicles Carrying APOE Downregulate Filament Actin Polymerization Signaling to Inhibit Synapse Formation in Alzheimer's Disease.},
journal = {Journal of extracellular vesicles},
volume = {15},
number = {3},
pages = {e70248},
doi = {10.1002/jev2.70248},
pmid = {41806350},
issn = {2001-3078},
support = {D2502003//Shenzhen Medical Research Fund/ ; 32200638//National Natural Science Foundation of China/ ; 32400813//National Natural Science Foundation of China/ ; 2023A1515010090//Basic and Applied Basic Research Fund of Guangdong Province/ ; JCYJ20230807110316034//Shenzhen Science and Technology Innovation Program/ ; JCYJ20240813150253048//Shenzhen Science and Technology Innovation Program/ ; JCYJ20250604143710014//Shenzhen Science and Technology Innovation Program/ ; ZSQYBRJH0021//Research Start-up Fund of the Seventh Affiliated Hospital, Sun Yat-sen University/ ; ZDSYS20220606100801003//Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research/ ; },
abstract = {Synaptic formation impairment is closely correlated with cognitive impairment in Alzheimer's disease (AD), yet the underlying mechanisms remain incompletely understood. Emerging evidence indicates that extracellular vesicles (EVs), critical mediators of intercellular communication, are implicated in the progression of AD. However, the specific mechanisms through which neuron-derived EVs contribute to synaptic formation impairment in AD remain unexplored. In this study, we characterized EVs derived from primary neurons of APP/PS1 transgenic mice (APPNEVs) and investigated their impact on synapse formation. Transmission electron microscopy, nanoparticle flow cytometry, and immunoblotting confirmed that APPNEVs and WT neuron-derived EVs (WTNEVs) had similar morphology, size, and canonical small EVs markers. We further revealed that APPNEVs significantly impaired neuronal synapse formation by downregulating synaptic proteins PSD95 and Synaptophysin (SYP), reducing total synapse number, and shifting synapse morphology toward immature states. Proteomic profiling via mass spectrometry identified APOE as a key upregulated protein in APPNEVs. Pharmacological inhibition of APOE with EZ-482 effectively prevented APPNEV-induced synaptic formation impairment, APPNEV-mediated downregulation of synaptic proteins, and the APPNEV-induced decrease in synaptic maturity. Mechanistically, APPNEVs suppressed Rac1-N-WASP-Arp2/3-mediated filament actin polymerization, a critical pathway for synaptic spine formation, which was prevented by APOE inhibition. In vivo stereotactic injection of APPNEVs into the hippocampus of WT mice further validated their detrimental effects on synaptic integrity, which were prevented by EZ-482 treatment. Collectively, these findings demonstrate that APPNEVs mediate synaptic damage via carrying APOE, providing novel insights into EV-mediated neurodegeneration in AD and highlighting APOE as a potential therapeutic target for preserving synaptic formation.},
}

@article {pmid41806233,
year = {2026},
author = {Yang, D and Wei, R and Zhu, J and Chen, J and Wang, S and Cai, H and Zhang, B and Teng, B and Li, B and Xie, X and Huang, S and Weng, Y and Chen, G},
title = {Class-Specific Antihypertensives and Alzheimer's Disease: Genotype- and Hypertension-Stratified Analysis.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41806233},
issn = {1559-1182},
abstract = {Antihypertensive medications (AHMs) may modulate Alzheimer's disease (AD) pathogenesis via cerebrovascular or neuroinflammatory pathways, yet evidence remains conflicting. This study investigated causal associations between AHM use and AD risk, focusing on drug classes, blood pressure status, and apolipoprotein E epsilon 4 (APOE ε4) effects. We integrated genetic causal inference with longitudinal survival analyses in a dual-evidence framework. Mendelian randomization (MR) was used to estimate class-specific causal effects at the population level. To examine effect modification by genetic and clinical factors, we analyzed 532 cognitively normal or mildly impaired older adults in ADNI with baseline assessments, with time-to-AD conversion modeled using Cox regression stratified by hypertension history and APOE ε4 status. Overall antihypertensive use showed no significant association with AD risk in hypertensive individuals (HR = 0.71) or APOE ε4 carriers (HR = 0.72). However, ARBs demonstrated protective associations in APOE ε4 carriers (HR = 0.32, 95% CI: 0.12-0.86). MR analysis supported causal protective effects for angiotensin II receptor blockers (ARBs, OR = 0.94, 95% CI: 0.89-0.98), calcium channel blockers (CCBs, OR = 0.93, 95% CI: 0.90-0.97), and beta-blockers (BBs, OR = 0.92, 95% CI: 0.86-0.98), whereas ACEIs lacked MR support and thiazide diuretics showed no benefit. Our findings reveal class-specific antihypertensive effects on AD risk. ARBs demonstrated the strongest protection, particularly in APOE ε4 carriers, while BBs and CCBs showed neuroprotective benefits. Results suggest AD prevention involves mechanisms beyond blood pressure reduction alone, supporting precision medicine with genotype-guided antihypertensive selection for genetically vulnerable individuals.},
}

@article {pmid41806092,
year = {2026},
author = {Djebari, S and Contreras, A and Castro-Andrés, V and Jimenez-Herrera, R and Iborra-Lázaro, G and Sánchez-Campusano, R and Jiménez-Díaz, L and Navarro-López, JD},
title = {Posterior parietal cortex oscillatory activity reflects persistent spatial memory impairments induced by early hippocampal amyloidosis in male mice.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP286196},
pmid = {41806092},
issn = {1469-7793},
support = {PID2020-115823-GBI00//MCIN/AEI/10.13039/501100011033/ ; PID2024-155413NB-I00//MCIN/AEI/10.13039/501100011033/ ; SBPLY/21/180501/000150//JCCM/ERDF/ ; SBPLY/24/180225/000181//JCCM/ERDF/ ; 2022-GRIN-34354//UCLM/ERDF/ ; 2025-GRIN-38530//UCLM/ERDF/ ; UPO-1380660//ANDALUSIA/ERDF/ ; PID2022-141997NB-I00//MCIN/AEI/ ; 2021-MS-20549//Margarita Salas Postdoctoral Research Fellow/ ; //European Union NextGenerationEU/PRTR/ ; //UCLM/ESF Plan Propio de Investigación Programme/ ; },
abstract = {In early stages of Alzheimer's disease (AD), soluble amyloid-β (Aβ) is a key player disrupting neuronal activity and contributing to cognitive decline in advanced stages of the disease. Although the hippocampus has been a central focus in prior research because of its susceptibility to Aβ-induced alterations, a comprehensive understanding of the temporal progression of early AD pathology requires exploring interconnected brain regions. The posterior parietal cortex (PPC), collaborating closely with the hippocampus and involved in various memory processes, particularly spatial memory formation, holds particular significance. Investigating the function of the PPC is imperative because it may contribute to early AD characteristics and provide a more holistic perspective on disease progression. To address this gap, we examined the relationship between neural oscillations and memory processes in both the PPC and hippocampus, in a mouse model of early hippocampal amyloidosis generated by intracerebroventricular oligomeric Aβ1-42 (oAβ1-42) injection. By performing in vivo oscillatory activity recordings from these regions in alert animals, together with spatial and habituation memory tests (Barnes maze and open field habituation), we found oAβ1-42 to induce significant alterations in PPC oscillatory activity. These changes emerged several days after hippocampal disturbances showed as aberrant synaptic plasticity and network activity. Additionally, significant alterations of stereotyped behaviours were not found. Our results provide an electrophysiological substrate for persistent spatial memory deficits and the temporal progression pattern of the early deleterious effects caused by Aβ. Furthermore, investigating PPC oscillatory activity might be a valuable approach for early detection and intervention in AD. KEY POINTS: Posterior parietal cortex (PPC), in close collaboration with the hippocampus, has been implicated in various memory processes disrupted in early Alzheimer's disease models. A mouse model of early Alzheimer's-like hippocampal amyloidosis generated by intracerebroventricular oligomeric Aβ1-42 (oAβ1 42) injection was used to examine the relationship between neural oscillations and memory processes in both the PPC and hippocampus. oAβ1-42 induces alterations in spatial and habituation memory, associated with PPC aberrant oscillatory activity, several days after hippocampal synaptic plasticity and network activity disturbances were found. We provide an electrophysiological PPC-mediated substrate for persistent spatial memory deficits and the temporal progression pattern of the early oscillatory deleterious effects caused by Aβ.},
}

@article {pmid41805579,
year = {2026},
author = {Yang, Y and Zhao, W and Mao, Y and Mao, T and Deng, Y and Yang, Y and Rao, H and Liu, X},
title = {Sleep deprivation exhibits an age-dependent effect on infraslow global brain activity.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {11},
pages = {e2528913123},
doi = {10.1073/pnas.2528913123},
pmid = {41805579},
issn = {1091-6490},
support = {1RF1MH123247//HHS | NIH | BRAIN Initiative (The BRAIN Initiative)/ ; 1R01NS113889//NIH R01/ ; R01-HL102119//NIH R01/ ; },
mesh = {*Sleep Deprivation/physiopathology/cerebrospinal fluid ; Humans ; *Brain/physiopathology/physiology/diagnostic imaging ; Adult ; Magnetic Resonance Imaging ; Middle Aged ; Male ; *Aging/physiology ; Female ; Sleep/physiology ; },
abstract = {Infraslow (<0.1 Hz) global brain activity, quantified by the global mean blood-oxygenation-level-dependent (gBOLD) signal in resting-state functional magnetic resonance imaging (fMRI), is elevated during sleep and coupled to cerebrospinal fluid (CSF) dynamics, a key pathway for the brain waste clearance implicated in neurodegenerative disorders such as Alzheimer's disease. However, the effect of sleep deprivation on gBOLD activity and its interaction with aging remain poorly understood. Using a rigorously controlled in-laboratory total sleep deprivation (TSD) protocol, we demonstrate that TSD significantly increases both the gBOLD signal amplitude and its coupling with CSF flow, suggesting a compensatory mechanism that may enhance glymphatic clearance following acute sleep loss. Notably, these TSD-induced enhancements exhibit robust age dependency, with markedly attenuated responses in midlife adults (40 to 50 y). The absence of this compensatory mechanism in midlife may exacerbate age-related impairments in neurotoxic clearance and increase dementia susceptibility, thereby offering mechanistic insights into the nexus between sleep disruption, aging, and neurodegeneration.},
}

*Sleep Deprivation/physiopathology/cerebrospinal fluid
Humans
*Brain/physiopathology/physiology/diagnostic imaging
Adult
Magnetic Resonance Imaging
Middle Aged
Male
*Aging/physiology
Female
Sleep/physiology

@article {pmid41805528,
year = {2026},
author = {Liu, C and Li, W and Wang, S and Wang, J and Wang, J and Wu, H and Loparo, KA and Fietkiewicz, C},
title = {A Push-Pull Network Mechanism Revealed by Describing Function Analysis for Alzheimer's Pathological Oscillations.},
journal = {IEEE transactions on neural networks and learning systems},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TNNLS.2026.3666557},
pmid = {41805528},
issn = {2162-2388},
abstract = {Abnormal theta band (4-8 Hz) cortical oscillations have been identified as a pathological hallmark in Alzheimer's disease (AD), which can be suppressed through high-frequency electrical stimulation (ES). However, their neural origins and mechanistic underpinnings remain poorly understood. In this work, we develop a mathematical model to characterize AD-related cortical theta oscillations. Through linear equivalent transformation of the physiological model and describing function analysis, we elucidate the network mechanism underlying these pathological oscillations. The results demonstrate that the reduced synaptic inhibition from fast inhibitory interneurons to pyramidal neuron populations drives the cortical network into a pathological low-frequency (theta band) oscillatory state. The oscillation frequency and amplitude can be directly determined from the intersection points between the Nyquist curve of the model's linear component and the negative inverse curve of the nonlinear element's describing function. Conversely, the separation between these curves driven by external stimulation visually represents how stimulation can shift the cortical network away from abnormal theta oscillations. The describing function analysis not only provides a mechanistic explanation for aberrant oscillations but also enables precise prediction of effective stimulation parameters for suppressing pathological theta activity. This work offers a novel framework to reveal the "push-pull" network effects of AD, providing an intuitive understanding of cortical stimulation mechanisms and a quantitative approach for optimizing neuromodulation strategies in AD.},
}

@article {pmid41805504,
year = {2026},
author = {Feng, L and Ai, Y and Zhou, Z and Zhai, Y and Yue, C and Wang, W and Yao, D and Valdes-Sosa, PA and Ren, P},
title = {Multiscale Node-Edge Interactions in Complex Networks: A Case Study Using Brain Network.},
journal = {IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TNSRE.2026.3672459},
pmid = {41805504},
issn = {1558-0210},
abstract = {OBJECTIVE: In complex networks, researching the relationships between nodes and edges has been a hot topic in recent years. However, to date, no studies have explored the multiscale node-edge interaction (MNEI) information within complex networks.

METHOD: As an illustrative example, the study employs brain networks of individuals diagnosed with Alzheimer's disease, mild cognitive impairment, and healthy controls. Our approach begins by decomposing the node and edge attributes from the vertex domain into nine MNEI components within the graph frequency domain. Each component encapsulates joint information, integrating either high, middle, or low graph frequency bands for node attributes, along with any band from the edge attributes. Following this, we transform each MNEI component back into the vertex domain to enable further analysis. Ultimately, the MNEI features derived from both domains are employed to classify subjects into three distinct groups.

RESULTS: A majority of MNEI features display significant differences among the groups, resulting in classification performance that surpasses traditional brain network analysis methods.

CONCLUSION: Importantly, this study is the first to demonstrate the capability of capturing MNEI in complex networks. Additionally, this research can be regarded as a novel information fusion technique for integrating node and edge attributes under non-Euclidean network topological constraints. Furthermore, this approach can also be considered a new type of multi-scale complex network decomposition.

SIGNIFICANCE: Overall, these advancements have expanded the scope of complex network analysis and provided brand-new scientific insights, with the potential for widespread application in numerous fields in the future.},
}

@article {pmid41805402,
year = {2026},
author = {Clark, AL and Asimakopoulos, G and Valocchi, E and Chanfreau-Coffinier, C and McGill, M and Thomas, KR and Jester, DJ and Logue, MW and Merritt, VC},
title = {Individual-Level Factors Associated With 10-Year Incidence of Alzheimer Disease and Related Dementias in the VA Million Veteran Program.},
journal = {Neurology},
volume = {106},
number = {7},
pages = {e214748},
doi = {10.1212/WNL.0000000000214748},
pmid = {41805402},
issn = {1526-632X},
abstract = {BACKGROUND AND OBJECTIVES: Approximately 450,000 Veterans are living with Alzheimer disease and related dementias (ADRD), and the high prevalence of ADRD represents a major public health challenge for the Veterans Health Administration. While advancing age and genetic predisposition are well-established ADRD risk factors, growing evidence suggests that additional modifiable factors may also play an important role. This study leveraged data from the VA Million Veteran Program (MVP) to (1) estimate 10-year incidence of ADRD and (2) evaluate associations between a broad range of individual-level risk and resilience factors and incident ADRD in a large, nationally representative sample of Veterans.

METHODS: This retrospective cohort study included Veterans aged ≥65 years at MVP enrollment who completed the MVP Baseline Survey and had VA electronic health record (EHR) data available. Individual-level variables including sociodemographic factors, military-specific characteristics, military environmental exposures (MEEs), health conditions, and health behaviors were characterized using MVP Baseline Survey data and supplemented with EHR data as available. The primary outcome was ADRD, which was determined using a validated algorithm based on International Classification of Diseases diagnosis codes extracted from the EHR. Associations between each risk/resilience factor and incident ADRD were examined using separate Cox regression models adjusted for age, sex, and education.

RESULTS: The sample included 245,949 Veterans (age: mean 73.16, SD 6.84 years; 2.59% female). Approximately 4.56% (n = 11,216) of the sample developed ADRD over 10 years. History of traumatic brain injury (TBI; hazard ratio [HR] 2.96, 95% CI 2.76-3.17), depression (HR 2.93, 95% CI 2.82-3.04), and alcohol use disorder (AUD; HR 2.35, 95% CI 2.19-2.53) were the health factors most strongly associated with ADRD. ADRD risk was also elevated among Veterans with a history of exposure to Agent Orange (HR 1.09, 95% CI 1.03-1.14), chemical/biological warfare agents (HR 1.31, 95% CI 1.23-1.39), and pyridostigmine bromide tablets (HR 1.67, 95% CI 1.44-1.93).

DISCUSSION: Findings identified TBI, depression, AUD, and MEEs as key variables associated with ADRD in Veterans. These factors may represent important targets for prevention and intervention efforts aimed at improving the long-term health of aging Veterans. Additional work is needed to clarify the mechanisms through which these factors influence ADRD risk and to establish whether observed associations are causal.},
}

@article {pmid41805251,
year = {2026},
author = {Zhou, H and Zhao, X and Li, Y and Wang, Y and Zhang, S and Xu, H and Sui, S and Wang, Q and He, Y and Gu, J},
title = {Nicotinamide mononucleotide supplementation modulates gut microbiota and metabolites to mitigate Alzheimer's disease pathology in APP/PS1 mice.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261422502},
doi = {10.1177/13872877261422502},
pmid = {41805251},
issn = {1875-8908},
abstract = {BackgroundEmerging evidence indicates that gut microbiome dysbiosis may be linked to Nicotinamide adenine dinucleotide (NAD[+]) deficiency during Alzheimer's disease (AD) progression, a condition potentially alleviated by nicotinamide mononucleotide (NMN) supplementation.ObjectiveTo explore the therapeutic potential of NMN supplementation in regulating AD pathology as well as gut microbiome dynamics, APP/PS1 transgenic mouse models were employed in the research.MethodsMetagenomic and metabolomics analysis were conducted to assess modifications in the intestinal microbiota and metabolites of AD mice post-NMN treatment. Moreover, immunohistochemistry, immunofluorescence, western blot, and Morris water maze were applied to evaluate NMN's ameliorative effects on AD.ResultsNMN administration significantly altered gut microbial composition and fecal metabolite profiles, leading to improvements in colon damage and AD-related neuropathology. Key findings include the restoration of gut microbial balance, particularly increasing Bacteroides abundance, and the modulation of metabolites involved in lipid metabolism. Furthermore, NMN was found to regulate ferroptosis, improving gut barrier function in AD mice, which were mediated through gut-brain communication pathways. NMN supplementation also enhanced ATP production, mitochondrial function, and synaptic density in the hippocampus while reducing oxidative stress and Aβ accumulation in the brain. Ultimately, these multi-faceted improvements collectively alleviated cognitive deficits in AD mice.ConclusionsIn summary, NMN supplementation effectively modulated gut microbiota and metabolites, thus mitigating AD pathology in APP/PS1 mice. Our study offers novel perspectives on the mechanisms underlying NMN's therapeutic effects in AD and underlines its potential as a promising intervention strategy.},
}

@article {pmid41805243,
year = {2026},
author = {Chutia, P and Tripathi, SM and Supranjali, S},
title = {Effect of Low-dose Escitalopram on Cognition and Behavior of Patients With Dementia Without Depression: A Retrospective Study.},
journal = {Clinical neuropharmacology},
volume = {},
number = {},
pages = {},
pmid = {41805243},
issn = {1537-162X},
abstract = {OBJECTIVE: The role of escitalopram on cognition in patients with dementia is inconclusive. In this study effect of low-dose escitalopram on cognition in subjects with dementia without depression is explored.

METHODS: This is a retrospective study of subjects aged 60 years or more with a diagnosis of dementia without depression conducted in a tertiary-care hospital in India. Subjects treated with low-dose escitalopram with a follow-up of 12 weeks duration were included. The parameters extracted were sociodemographic characteristics, duration and type of dementia, comorbidities, other psychotropics, and antidementia drugs. The change in Hindi Mental Status Examination score from baseline to fourth, eighth, and 12th weeks is considered the primary outcome measure. In addition, changes in neuropsychiatric symptoms are the secondary outcome measures. Statistical methods include descriptive and comparative analysis, and repeated measures ANOVA was applied to assess change in cognition over time.

RESULTS: A total of 44 subjects were included, with a mean age of 73.5 ± 7.42 years and 56.82%. Among the subjects, 79.55% were diagnosed with AD, 11.36% with FTD, and 9.09% with VD, and the average duration of illness was 4.48 ± 2.28 years. Comparison of HMSE score from baseline to fourth, eighth, and 12th week shows a significant difference with P <0.001, with greater improvement in the first 4 weeks. In addition, the NPI and ADL scores showed significant improvement in week-4 with P <0.001.

CONCLUSION: Escitalopram shows a promising effect on cognition, behaviour, and functionality in subjects with dementia in the short term. However, a larger prospective long-term study is needed to validate the study findings.},
}

@article {pmid41805006,
year = {2026},
author = {Özyılmaz, ED},
title = {A Nasal Hydrogel Combining Metformin and Curcumin for Potential Nose-to-Brain Therapy in Neurodegenerative Disorders.},
journal = {Assay and drug development technologies},
volume = {},
number = {},
pages = {1540658X261429259},
doi = {10.1177/1540658X261429259},
pmid = {41805006},
issn = {1557-8127},
abstract = {Neurodegenerative disorders such as Alzheimer's and Parkinson's disease remain a significant therapeutic challenge due to the restrictive nature of the blood-brain barrier (BBB) and the limited efficacy of current pharmacological treatments. Intranasal administration has emerged as a promising noninvasive strategy that enables direct drug delivery to the brain by bypassing the BBB. This study aimed to design and optimize a dual-drug nasal hydrogel containing metformin hydrochloride, a hydrophilic AMP-activated protein kinase activator, and curcumin, a lipophilic antioxidant and anti-amyloid agent, and to provide synergistic neuroprotection. The formulation was prepared using carbopol as the gel matrix and characterized in terms of physicochemical stability, drug content uniformity, rheology, in vitro release, and excipient compatibility. A Box-Behnken design was used to systematically evaluate the effects of carbopol, glycerin, and curcumin concentrations on critical quality attributes. The optimized hydrogel exhibited acceptable pH, viscosity suitable for nasal administration, and sustained biphasic drug release with a cumulative 6-h release of approximately 85% for metformin and 39% for curcumin according to the Higuchi drug release model (R[2] > 0.98). Collectively, these results highlight the feasibility of an integrative intranasal hydrogel platform to overcome the bioavailability challenges of both agents. The proposed system offers a patient-friendly, noninvasive approach for potential nose-to-brain therapy in neurodegenerative disorders and warrants further preclinical and in vivo investigation.},
}

@article {pmid41804872,
year = {2026},
author = {Özcan, GG and Rihel, J},
title = {Modeling diseases of aging in larval zebrafish, a paradoxical yet powerful strategy.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyag027},
pmid = {41804872},
issn = {1943-2631},
support = {//Alzheimer's Research/ ; #217150/Z/19/Z//Wellcome Trust Investigator Award/ ; },
abstract = {Neurodegenerative diseases are a set of devastating medical conditions in which neuronal loss associated with the aggregation of toxic proteins leads to progressive cognitive impairment. These diseases are usually modeled in animals by mimicking late disease stages through genetic modifications that aggressively accumulate proteins that damage the brain. However, these diseases typically unfold over decades, and disease-associated genes are known to have important, but understudied, biological functions in early life stages. To address this research gap, we suggest that the larval zebrafish, which has conserved orthologs of most neurodegeneration-linked genes, is an excellent model to examine early mechanisms that set the stage for disease progression, such as altered neuronal function, synaptic re-wiring, and proteostasis. We propose a systematic genetic modeling and phenotyping pipeline in zebrafish that integrates CRISPR editing, high-throughput behavioral assays, brain-wide activity mapping, and pharmacological screens to capture neurodegenerative disease-related changes that occur well before clinical disease emerges. Studying diseases of aging in larval zebrafish may sound paradoxical; however, by uncovering cellular dysfunction at the earliest stages of disease in a living vertebrate brain, this approach could identify critical therapeutic targets at timepoints before degeneration becomes irreversible.},
}

@article {pmid41804868,
year = {2026},
author = {Hashimoto, S and Matsuba, Y and Takahashi, M and Saido, TC},
title = {Tau acetylation at K331 has limited impact on tau pathology in vivo.},
journal = {FEBS letters},
volume = {},
number = {},
pages = {},
doi = {10.1002/1873-3468.70320},
pmid = {41804868},
issn = {1873-3468},
support = {JP22H05037//Japan Society for the Promotion of Science/ ; JP23K06407//Japan Society for the Promotion of Science/ ; JPMJPF2018//Co-creation place formation support program/ ; },
abstract = {Post-translational modifications regulate tau aggregation and propagation, yet how amyloid pathology shapes the tau modification landscape remains unclear. Using liquid chromatography-tandem mass spectrometry, we compared tau modifications in MAPT knock-in (MAPT KI) mice and MAPT/App double knock-in mice with App[NL-G-F] amyloid pathology. Only subtle differences were detected, with a tendency toward increased acetylation within the repeat domain. Because K321 and K331 lie in the fibril-forming core, their roles were further examined. Acetylation at these sites was absent in cynomolgus monkey brains. To test functional relevance, we generated acetylation-mimicking MAPT[K331Q] knock-in mice on the MAPT KI background. Despite tau expression, these mice showed reduced tau phosphorylation at 24 months, with unchanged insoluble tau and seeding activity. Thus, K331 acetylation does not promote tau pathology.},
}

@article {pmid41804841,
year = {2026},
author = {Kim, JP and Song, M and Cho, M and Lee, H and Jung, SH and Lim, S and Kim, C and Jang, B and Shin, D and Kang, H and Yim, S and Jang, H and Kim, BH and Kim, HJ and Na, DL and An, JY and Zetterberg, H and Blennow, K and Gonzalez-Ortiz, F and Ashton, NJ and Day, TA and Seo, SW and Won, HH},
title = {Genetic architecture of plasma pTau217 and related biomarkers in Alzheimer's disease via genome-wide association studies.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71275},
doi = {10.1002/alz.71275},
pmid = {41804841},
issn = {1552-5279},
support = {RS-2025-25466827//Ministry of SMEs and Startups (MSS)/ ; RS-2020-KH106434//Korea Dementia Research Project through the Korea Dementia Research Center (KDRC)/ ; RS-2025-02223212//Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)/ ; RS-2025-25455095//Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)/ ; 2019-NR040057//National Research Foundation of Korea (NRF)/ ; RS-2023-00247408//National Research Foundation of Korea (NRF)/ ; RS-2023-00262527//National Research Foundation of Korea (NRF)/ ; 2023-ER1001-03// Korea National Institute of Health/ ; 2024-ER1003-02// Korea National Institute of Health/ ; 2025-ER1003-00// Korea National Institute of Health/ ; },
mesh = {Humans ; Genome-Wide Association Study ; *Alzheimer Disease/genetics/blood ; *tau Proteins/blood/genetics ; Biomarkers/blood ; Male ; Female ; Aged ; Glial Fibrillary Acidic Protein/blood ; Neurofilament Proteins/blood ; Republic of Korea ; Mendelian Randomization Analysis ; Quantitative Trait Loci ; },
abstract = {INTRODUCTION: We aimed to define the genetic architecture and regulatory mechanisms of Alzheimer's disease (AD) -related plasma biomarkers in an East Asian population.

METHODS: Genome-wide association studies (GWAS) of plasma phosphorylated tau at threonine 217 (pTau217), pTau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were performed in 1,972 individuals from the Korea-Registries to Overcome and Accelerate Dementia Research (K-ROAD) cohort. Results were integrated with Korean single-nucleus transcriptomics, AD-relevant brain quantitative trait loci resources, and summary-based Mendelian randomization (SMR) and colocalization analyses.

RESULTS: Genome-wide significant loci were identified for all biomarkers, including DACT1-DAAM1 (pTau217), KCNJ3 (pTau181), KLHDC4 (NfL), SLC10A7 (GFAP), and PPP4R2 (composite score). Strong associations at the apolipoprotein E locus were observed across biomarkers. Integrative analyses implicated DACT1 as a key regulatory mediator of pTau217, particularly in oligodendrocytes.

DISCUSSION: These findings link ancestry-relevant AD biomarker genetics to brain regulatory mechanisms and support integrative causal analyses.},
}

Humans
Genome-Wide Association Study
*Alzheimer Disease/genetics/blood
*tau Proteins/blood/genetics
Biomarkers/blood
Male
Female
Aged
Glial Fibrillary Acidic Protein/blood
Neurofilament Proteins/blood
Republic of Korea
Mendelian Randomization Analysis
Quantitative Trait Loci

@article {pmid41804834,
year = {2026},
author = {Chen, S and Hao, X and Ma, K and Li, R and Wen, C and Han, X and Zheng, W and Ruan, S and You, S and An, W and Qi, Z and Wang, K and He, W and Duan, Z and Wang, F and Shang, J and Cao, L and Hao, Y and Zhang, J},
title = {Implementing plasma p-tau217 and cognitive testing for Alzheimer's screening in low-education populations in central China.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71251},
doi = {10.1002/alz.71251},
pmid = {41804834},
issn = {1552-5279},
support = {241111313500//Henan Province Key R&D Program/ ; 82201471// National Natural Science Foundation of China/ ; },
mesh = {Humans ; Aged ; Female ; *tau Proteins/blood ; Male ; China/epidemiology ; *Alzheimer Disease/diagnosis/blood ; Biomarkers/blood ; Middle Aged ; Neuropsychological Tests ; *Cognitive Dysfunction/diagnosis/blood ; Educational Status ; Aged, 80 and over ; Phosphorylation ; Cohort Studies ; Mass Screening ; },
abstract = {INTRODUCTION: We evaluated a pragmatic screening strategy combining brief cognitive assessment with plasma phosphorylated tau217 (p-tau217) in an elderly health screening cohort.

METHODS: Participants completed the Memory and Executive Screening (MES) test and plasma biomarker assessment. Cognitive impairment was defined using individualized residual norms derived from an internal reference sample. The p-tau217 thresholds were positive predictive value (PPV) -oriented and anchored to age- and cognitive status-specific prior probabilities of amyloid-β (Aβ) pathology.

RESULTS: MES-defined cognitive impairment (≤-2 standard deviation [SD] deviation after adjustment for demographics) was identified in 12.4% of participants. In cognitively unimpaired (CU) individuals, age-specific thresholds targeting a PPV of 0.7 yielded an overall p-tau217 positivity rate of 11.8%, increasing from 3.5% (< 60 years) to 6.3% (60-70 years) and 25.9% (≥70 years). Among cognitively impaired (CI) participants, 26.6% were p-tau217 positive.

DISCUSSION: This framework supports practical integration of plasma biomarkers into community-based screening, with longitudinal follow-up needed to further refine threshold selection.

HIGHLIGHTS: Regression-based residual method reduced education bias, identifying 12.4% with cognitive impairment individuals. Fully automated chemiluminescent assay enabled practical, large-scale biomarker implementation. Brief screening strategy supports early detection, clinical trial recruitment, and resource allocation in under-resourced regions.},
}

Humans
Aged
Female
*tau Proteins/blood
Male
China/epidemiology
*Alzheimer Disease/diagnosis/blood
Biomarkers/blood
Middle Aged
Neuropsychological Tests
*Cognitive Dysfunction/diagnosis/blood
Educational Status
Aged, 80 and over
Phosphorylation
Cohort Studies
Mass Screening

@article {pmid41804798,
year = {2026},
author = {Jagaraj, CJ and Saravanabavan, S and Parakh, S and Jayakumar, M and Kashani, SA and Shadfar, S and Mehta, P and Gautam, S and Farzana, F and Suchowerska, AK and Yap, K and Vidal, M and Ragagnin, AMG and Jamali, MS and Yang, S and Fath, T and Craik, D and Atkin, JD},
title = {Cofilin hyperphosphorylation triggers TDP-43 pathology in sporadic amyotrophic lateral sclerosis.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag096},
pmid = {41804798},
issn = {1460-2156},
abstract = {Pathological forms of TAR-binding protein 43 (TDP-43), involving its aberrant mislocalization to the cytoplasm, inclusion formation, hyperphosphorylation and fragmentation, are present in ∼45-50% frontotemporal dementia (FTD) and Alzheimer's disease individuals, and most (97%) amyotrophic lateral sclerosis (ALS) cases. Hence, identifying mechanisms that induce TDP-43 pathology are central to neurodegeneration and developing new therapeutic targets in these conditions. Cofilin is a multi-functional protein with a crucial role in regulating the actin cytoskeleton. Actin has important neuronal-specific activities in dendritic spines, axonal growth cones and synapses and it is in constant equilibrium between two forms: monomeric globular actin (G-actin) and polymeric filamentous actin (F-actin). Cofilin controls actin dynamics by depolymerising and severing actin filaments. When cofilin is phosphorylated (at Serine-3) by LIM kinase1 (LIMK1), it becomes inactive, leading to production of more F-actin. Defects in cofilin are well described in other neurodegenerative disorders, unlike in ALS. We examined phosphorylation of cofilin and actin dynamics in post-mortem spinal cord tissue from sporadic ALS (SALS) patients, the TDP-43 rNLS8 transgenic mouse model, and NSC34 motor neuronal cells expressing cytoplasmic TDP-43. F-actin was pharmacologically stabilized to mimic cofilin hyperphosphorylation, and TDP-43 pathology was assessed. Neuronal cells were treated with a non-phosphorylatable cofilin S3A peptide (MAAGVAVSDGVIKVFN), and TDP-43 pathology and apoptosis were evaluated. Here, we show that cofilin is hyper-phosphorylated in human ALS and disease models compared to controls. This was detected in spinal motor neurons from sporadic ALS (SALS) patients and a TDP-43 mouse model (rNLS8) displaying key ALS phenotypes, and in motor neuronal NSC34-cells expressing cytoplasmic TDP-43. Supporting this observation, more F-actin relative to G-actin was present in cortical/spinal cord lysates from SALS patients and TDP-43 rNLS8 mice, and NSC34-cells expressing TDP-43. We also show that mimicking cofilin hyperphosphorylation by pharmacological stabilization of F-actin induced TDP-43 pathology: cytoplasmic mislocalization, inclusion formation, hyperphosphorylation, and fragmentation, and promoted its recruitment into stress granules (SGs). Furthermore, we detected increased levels of LIMK1 phosphorylation and tropomyosin isoforms 4.1 and 4.2 in SALS patients. These findings reveal aberrant cofilin hyperphosphorylation disrupts actin dynamics, triggering TDP-43 pathology and SG recruitment in SALS. They imply that preventing cofilin phosphorylation is a novel therapeutic strategy applicable to most ALS cases. Treatment of neuronal cells with the S3A peptide prevented features of TDP-43 pathology and apoptosis compared to control peptides. These findings thus describe a novel pathogenic mechanism producing TDP-43 pathology, applicable to most ALS cases and other neurodegenerative diseases.},
}

@article {pmid41804765,
year = {2026},
author = {Martinez-Pereira, A and Mistler, LA and Tarczewski, S and Arcila-Mesa, M and Rapozo, C and Chodosh, J and Barr, PJ},
title = {Using community engagement studios to involve persons living with dementia and their care partners in research design.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424394},
doi = {10.1177/13872877261424394},
pmid = {41804765},
issn = {1875-8908},
abstract = {BackgroundPersons living with dementia (PLWD) and their care partners face unique challenges in participating in research studies. Community Engagement Studios (CES) provide a framework for researchers to work directly with community members, considered as Community Experts, who experience conditions under study to enhance research design, implementation, and dissemination.ObjectiveWe describe our experience conducting CES with PLWD and their care partners and lessons learned.MethodsPLWD and their care partners participated in three CES between July and December 2022; one in New Hampshire in English and two in New York, one of which was in Spanish. We followed the CES Toolkit guidance, which involves 1) inviting experts/stakeholders (PLWD and their care partners) to a consultative meeting, 2) preparing a presentation (interview guide) and facilitating the meeting, and 3) receiving and analyzing feedback from participants.Results12 community members (6 PLWD and 6 care partners) participated in our three studios. Three study design factors were identified during the CES: recruitment process (trust and communication with the research team), participants' autonomy, and trust and communication with clinicians. Spanish language community members raised similar issues to those in the English-speaking CES. However, Spanish language participants also noted the potential impact of interpreters during clinic visits.ConclusionsCES were feasible, informative, and well-received by PLWD and led to changes in our study design. We describe strategies for engaging care partners and PLWD, Community Experts, to elicit valid and valuable recommendations for making research studies more relevant and impactful.},
}

@article {pmid41804764,
year = {2026},
author = {Mohammediyan, B and Baril, AA and Fajardo Valdez, A and St-Onge, F and Pichet Binette, A and Carrier, J and Geddes, MR and Ducharme, S and Montembeault, M and Soucy, JP and Breitner, J and Poirier, J and Villeneuve, S and , },
title = {Longitudinal association between sleep and Alzheimer's pathology.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71228},
doi = {10.1002/alz.71228},
pmid = {41804764},
issn = {1552-5279},
support = {//Weston Family Foundation/ ; //Brain Canada/ ; 35450//Quebec Bio-imaging Network Scholarship/ ; //CIUSSS-NIM (Bourse d'excellence du CIUSSS-NIM 2024)/ ; //Alzheimer Society of Canada/ ; 361227//Fonds de la recherche du Québec en Santé (FRQS)/ ; 153286//Fonds de la recherche du Québec en Santé (FRQS)/ ; //Sleep Research Society Foundation/ ; //Fondation de l'Institut de gériatrie de Montréal/ ; 451830//Canadian Institutes of Health Research (CIHR)/ ; 178210//Canadian Institutes of Health Research (CIHR)/ ; //Healthy Brains Healthy Lives McGill/ ; //Biogen Canada/ ; //Natural Sciences and Engineering Research Council of Canada/ ; //J.L. Levesque Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/diagnostic imaging ; Male ; Female ; Positron-Emission Tomography ; Longitudinal Studies ; Aged ; Actigraphy ; *Sleep Wake Disorders/complications ; *Sleep/physiology ; Cross-Sectional Studies ; *Brain/pathology/diagnostic imaging/metabolism ; tau Proteins/metabolism ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Since sleep disturbance is a modifiable risk factor for Alzheimer's disease (AD), we tested associations between sleep and AD pathology in cognitively unimpaired (CU) persons.

METHODS: We included 223 participants from the PREVENT-AD cohort with self-reported measures of sleep, objective actigraphy measures of sleep, and positron emission tomography (PET) scans for AD pathology quantification. Repeated PET scans (mean follow-up: 4.31 ± 0.55 years) were available for 103 participants. We conducted robust linear models (RLM) for cross-sectional analyses and RLMs using the annual change in AD pathology for longitudinal analyses.

RESULTS: All actigraphy-based sleep variability measures were associated with tau burden (duration: β = 0.121 [95% confidence interval {CI}&
#xa0;= 0.010; 0.232], p = 0.034; efficiency: 0.122 [0.010; 0.235], 0.033; fragmentation: 0.115 [0.010; 0.221], 0.033). Greater variability in sleep fragmentation was also associated with amyloid burden (0.074 [0.008; 0.140], 0.028), and variability in sleep efficiency portended amyloid burden and faster accumulation over time (0.075 [0.009; 0.141], 0.026; 0.164 [0.008; 0.320], 0.039; respectively).

DISCUSSION: Irregularity in sleep patterns is associated with higher pathological burden and faster amyloid accumulation.},
}

Humans
*Alzheimer Disease/pathology/diagnostic imaging
Male
Female
Positron-Emission Tomography
Longitudinal Studies
Aged
Actigraphy
*Sleep Wake Disorders/complications
*Sleep/physiology
Cross-Sectional Studies
*Brain/pathology/diagnostic imaging/metabolism
tau Proteins/metabolism
Aged, 80 and over

@article {pmid41804762,
year = {2026},
author = {Liu, R and Qi, X and Luo, H and Liu, Y and Xu, Z and Zwerling, J and Wu, B},
title = {Edentulism and risk of all-cause dementia and Alzheimer's disease: A competing risk analysis by cognitive status.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424215},
doi = {10.1177/13872877261424215},
pmid = {41804762},
issn = {1875-8908},
abstract = {BackgroundEdentulism is an irreversible marker of severe oral disease and systemic disadvantage, yet robust epidemiological evidence linking edentulism to clinically diagnosed dementia remains limited.ObjectiveThis study uses clinically diagnosed dementia outcomes, accounting for the competing risk of death, and examines whether edentulism is associated with dementia risk differently, depending on baseline cognitive status.MethodsWe conducted a matched-cohort study using 2006-2020 Health and Retirement Study and linked Medicare claims data. Our sample included 2927 edentulous and 12,857 dentate older adults without baseline dementia. We used Coarsened Exact Matching to balance socioeconomic factors between edentulous and dentate participants. Fine-Gray competing risk models were used to estimate associations between edentulism and the risk of all-cause dementia (ACD) and Alzheimer's disease (AD), with analyses stratified by baseline cognition (normal cognition versus cognitive impairment, no dementia [CIND]).ResultsEdentulism was significantly associated with a 21% higher risk of ACD in the total cohort (subdistribution hazard ratio (sHR) 1.21; 95% CI 1.12-1.32), consistent across normal cognition (sHR 1.21; 95% CI, 1.07-1.36) and CIND (sHR 1.22; 95% CI, 1.04-1,43) groups. For AD, edentulism was associated with a 33% higher risk in the total cohort (sHR 1.33; 95% CI 1.10-1.62). This association was pronounced among cognitively normal individuals (sHR, 1.69; 95% CI, 1.26-2.28) but not CIND group (sHR 1.18; 95% CI 0.81-1.72).ConclusionsEdentulism is independently associated with an increased risk of incident ACD, irrespective of baseline cognitive status. Its association with AD is specific to cognitively normal individuals, highlighting a potential window for oral health interventions in dementia prevention.},
}

@article {pmid41804756,
year = {2026},
author = {Ke, Z and Wang, B and Liang, R},
title = {Modulation of mitochondrial quality by exercise mimetics: A potential strategy for the prevention and treatment of Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424276},
doi = {10.1177/13872877261424276},
pmid = {41804756},
issn = {1875-8908},
abstract = {Decline in mitochondrial quality is a prominent pathological feature of Alzheimer's disease (AD), manifested by impaired energy metabolism, disrupted mitochondrial biogenesis, abnormal mitochondrial dynamics, and defective mitophagy. Increasing evidence indicates that mitochondrial dysfunction contributes to the exacerbation of amyloid-β (Aβ) deposition and tau protein hyperphosphorylation, thereby accelerating AD pathogenesis. Of particular interest, physical exercise has been shown to effectively enhance mitochondrial quality and help prevent or slow the progression of AD, largely through the activation of key signaling pathways such as adenosine monophosphate-activated protein kinase (AMPK) and sirtuin 1 (SIRT1). However, regular physical activity may not be feasible for individuals in the prodromal or clinical stages of AD. In this context, exercise mimetics-compounds that pharmacologically simulate the molecular effects of exercise-have emerged as a promising alternative intervention. This review analyzes the mechanistic roles of exercise mimetics in improving mitochondrial quality under AD conditions, with a focus on their regulation of mitochondrial homeostasis via key signaling pathways. It further aims to provide theoretical insight for the development of mitochondria-targeted exercise mimetics and offer a potential strategy for addressing the growing global burden of AD.},
}

@article {pmid41804754,
year = {2026},
author = {Gogola, A and Cohen, AD and Lopresti, BJ and Ikonomovic, MD and Snitz, B and Tudorascu, D and Reese, A and Zeng, X and Minhas, D and Kofler, J and Matan, C and Aizenstein, H and Lopez, O and Karikari, TK and Villemagne, VL},
title = {Plasma amyloid-β predicts amyloid-β accumulation in PET A- non-demented participants.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261422406},
doi = {10.1177/13872877261422406},
pmid = {41804754},
issn = {1875-8908},
abstract = {BackgroundPlasma biomarkers for Alzheimer's disease (AD) studies, but much remains unknown about the associations of plasma and PET biomarkers of amyloid-β (Aβ).ObjectiveTo determine the associations of plasma Aβ with PET Aβ accumulation and progression from PET A- to A + .MethodsWe evaluated PET A- participants with baseline plasma Aβ measurements and longitudinal indices of PET Aβ. Linear mixed effects models characterized the association of plasma biomarker outcomes with changes in PET Aβ values. Survival analysis evaluated the ability of baseline plasma biomarker A+/- status to differentiate trajectories of progression from PET A- to A + .ResultsLinear mixed effects models showed significant interactions between time and plasma Aβ42/40 with respect to longitudinal measures of PET Aβ burden. Survival analysis found that A status determined from plasma Aβ42/40 predicted distinct patterns of progression from PET A- to A + .ConclusionsThese models suggest that, in PET A- participants, baseline plasma Aβ42/40 can be used to predict both how much Aβ will accumulate over time and likelihood of becoming PET A + .},
}

@article {pmid41804748,
year = {2026},
author = {Rice, M and Willoughby-Dudley, KA and Lin, M and Wang, H and Davalos, DB and , },
title = {Differential associations of cognitive screeners with biological, psychological, and cognitive factors in high-risk older adults.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424407},
doi = {10.1177/13872877261424407},
pmid = {41804748},
issn = {1875-8908},
abstract = {BACKGROUND: Dementia rates have accelerated in recent decades, yet our ability to screen for and predict who is at risk remains limited. The Montreal Cognitive Assessment (MoCA) and the Alzheimer's Disease Assessment Scale-Cog-13 item (ADAS-Cog-13) are common screeners that provide insight into early dementia progression. However, how these tools relate to biomarkers and psychological predictors before formal diagnosis is unclear.

OBJECTIVE: This study examines associations between biological and psychological factors with MoCA and ADAS-Cog-13 scores to guide clinicians in selecting the most informative screener for specific dementia risk profiles.

METHODS: Zero-order correlations and Classification and Regression Trees were conducted using data from the ADNI-DOD database, comprising high-risk veterans without baseline dementia.

RESULTS: MoCA scores were primarily associated with biomarker predictors and depression, whereas ADAS-Cog-13 scores were primarily associated with post-traumatic stress disorder diagnoses.

CONCLUSIONS: Cognitive screeners tailored to brief psychological and medical histories may improve early detection of cognitive decline and Alzheimer's disease.},
}

@article {pmid41804744,
year = {2026},
author = {Razouqi, Y and El-Abid, H and Khalki, L},
title = {Mapping dementia research in Morocco: A scoping review of epidemiological, genetic, and therapeutic evidence.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430304},
doi = {10.1177/13872877261430304},
pmid = {41804744},
issn = {1875-8908},
abstract = {BackgroundDementia represents a major global health challenge, particularly in low- and middle-income countries (LMICs). Morocco, facing rapid population ageing, lacks integrated epidemiological and translational research on Alzheimer's disease (AD) and related disorders.ObjectiveThis study aims to map Moroccan dementia studies and identify national advances and research gaps.MethodsFollowing PRISMA-ScR guidelines, a literature search was conducted in PubMed, Scopus, MEDLINE, and Web of Science covering the period 2000-2025. Studies including Moroccan samples and addressing dementia or AD in epidemiology, diagnostics, genetics, or therapy were retained. Thirty papers met criteria. Data were summarized narratively and organized in four thematic tables.ResultsMoroccan research spans four main pillars: (1) early-onset and clinical features; (2) validated cognitive assessment tools adapted to Arabic and Tamazight; (3) discovery of distinct APP, PSEN, and APOE mutations; and (4) emerging pharmacological and non-pharmacological interventions.ConclusionsThough still limited, Moroccan dementia research demonstrates scientific maturity and regional relevance. Establishing national registries, biobanks, and culturally tailored interventions will strengthen Africa's contribution to global neurodegenerative research.},
}

@article {pmid41804730,
year = {2026},
author = {Gupta, A and Anjali, A and Adhya, A and Vetal, D and Dubey, A and Tiwari, P and Gaikwad, S and Rajan, R and Vishnu, VY and Singh, MB and Bhatia, R and Srivastava, AK and Tripathi, M and Ramakrishnan, L and Tripathi, M},
title = {Clinical relevance of automated cerebrospinal fluid amyloid and tau biomarkers in Indian patients with early onset cognitive decline: Insights from the AIIMS-Delhi Study Cohort of Early/late oNset Dementia (ASCEND).},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261426905},
doi = {10.1177/13872877261426905},
pmid = {41804730},
issn = {1875-8908},
abstract = {Automated cerebrospinal fluid (CSF) biomarkers have been underexplored in early onset dementias (EOD) within the South-Asian context. In our ongoing ASCEND cohort (tertiary care center in India), we evaluated the added value of incorporating CSF amyloid-β 1-42 (Aβ42) and phosphorylated tau 181 (p-Tau181) (Elecsys immunoassay) into existing clinical diagnostic algorithms for EOD. Among 61 participants (mean age: 56.3 ± 5.8 years; 55.7% females), the CSF p-Tau181/Aβ42 ratio revealed alternative etiology in 16% of cases [5/37 (13.5%) clinically probable AD were reclassified as non-AD after CSF, while 5/24 (20.8%) clinically non-AD dementias were reclassified as AD]. Notably, clinico-biological concordance varied across different phenotypic presentations.},
}

@article {pmid41804728,
year = {2026},
author = {Ros, F and Martínez Lozano, MD and Arnau, J and Martínez, J and Vericat, A and Sánchez, R and Burgos, JS},
title = {Decreased interleukin-8 levels in the peripheral blood of Alzheimer's disease patients.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261428052},
doi = {10.1177/13872877261428052},
pmid = {41804728},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) has been reported to be associated with changes in inflammatory levels, although further research is needed. This study focused on identifying specific inflammatory biomarkers in peripheral blood that could differentiate patients with AD from healthy control subjects.ObjectiveThe primary objective was to determine whether a selection of peripheral blood inflammatory biomarkers could serve as a diagnostic tool for AD.MethodsA multicenter study was conducted, comparing 39 patients with AD to 27 healthy controls. AD diagnosis was confirmed through a comprehensive evaluation, including the Mini-Mental State Examination and analysis of cerebrospinal fluid or positron emission tomography. Thirteen inflammatory markers were measured, and logistic regression analysis was used to assess their discriminatory potential. The relationship between the APOE genotype and biomarker levels was also examined.ResultsThe analysis revealed that interleukin-8 (IL-8), platelet-derived growth factor (PDGF-AB/BB), and interleukin-12p40 (IL-12p40) were the most significant markers. IL-8 levels showed a strong correlation with disease status, being notably lower in AD patients compared to controls. Furthermore, the levels of these three markers were associated with the patient's amyloid-positive status of the APOE genotype.ConclusionsThese results suggest that reduced levels of IL-8 in the blood could be a promising biomarker for the diagnosis of AD. Additionally, inflammatory biomarkers such as IL-8 and IL-12p40 may be linked to the amyloid pathology of the APOE genotype in AD patients.},
}

@article {pmid41804725,
year = {2026},
author = {Hasan, Z and Torraville, SE and Omoluabi, T and Maziar, A and Belolise, ON and MacGowan, LA and Flynn, CM and Reinhardt, C and Walling, SG and Benoukraf, T and Yuan, Q},
title = {Sex and life experience shape locus coeruleus pretangle tau pathology.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71285},
doi = {10.1002/alz.71285},
pmid = {41804725},
issn = {1552-5279},
support = {#PJT-169197//Canadian Institutes of Health Research Project Grant/ ; #20-04//Alzheimer Society of Canada New Investigator Grant/ ; },
mesh = {Animals ; *Locus Coeruleus/pathology/metabolism ; Male ; Female ; *tau Proteins/metabolism ; Rats ; Humans ; Hippocampus/metabolism/pathology ; *Alzheimer Disease/pathology/metabolism ; Sex Factors ; Stress, Psychological ; *Tauopathies/pathology ; Sex Characteristics ; Neurons/metabolism/pathology ; },
abstract = {INTRODUCTION: Alzheimer's disease features early a pathology in the locus coeruleus (LC), yet how sex and life experience shape LC vulnerability remains poorly understood.

METHODS: We expressed pseudophosphorylated human tau (htauE14) in LC neurons of TH-Cre rats and exposed both sexes to early- or late-life enrichment or stress. Behavioral, histological, protein, and hippocampal single-nucleus RNA sequencing (snRNA-seq) analyses were performed.

RESULTS: LC-targeted htauE14 impaired learning and increased anxiety-like behavior. Early enrichment reduced htauE14 spread and LC microglia activation, elevated hippocampal brain-derived neurotrophic factor (BDNF), and improved olfactory learning in males. Late enrichment alleviated anxiety and enhanced spatial memory, whereas late stress exacerbated LC degeneration. Hippocampal snRNA-seq revealed sex- and cell type-specific transcriptional responses, with htauE14 preferentially engaging metabolic and synaptic pathways in females, effects amplified by early stress but stabilized by early enrichment. Late-life experiences primarily recruited homeostatic regulatory programs.

DISCUSSION: Sex and developmental history critically shape early LC tau-related vulnerability.},
}

Animals
*Locus Coeruleus/pathology/metabolism
Male
Female
*tau Proteins/metabolism
Rats
Humans
Hippocampus/metabolism/pathology
*Alzheimer Disease/pathology/metabolism
Sex Factors
Stress, Psychological
*Tauopathies/pathology
Sex Characteristics
Neurons/metabolism/pathology

@article {pmid41804553,
year = {2026},
author = {Krishnaswami, A and Jain, A and Dinh, H and Ha, RV and Canio, WC and Nanna, MG and Romero, A and Gilsanz, P and Aggarwal, NT and Mielke, MM and Maurer, MS and Yang, JY and Shin, ED and Patel, DM and Damluji, AA and Shah, AI},
title = {Baseline Dementia Prevalence and Subtypes in Older Adults Hospitalized With Acute Coronary Syndrome: A Multicenter Study From a Large Integrated Health Care Delivery System.},
journal = {The Permanente journal},
volume = {},
number = {},
pages = {1-9},
doi = {10.7812/TPP/25.159},
pmid = {41804553},
issn = {1552-5775},
abstract = {BACKGROUND: Dementia is increasingly common among older adults (≥ 65 years) and is associated with poor outcomes. However, little is known about its baseline prevalence in patients hospitalized with acute coronary syndrome (ACS), particularly across revascularization strategies.

METHODS: The authors conducted a cross-sectional analysis from a current longitudinal cohort study of Kaiser Permanente Northern California members hospitalized with ACS between January 2010 and December 2020. Dementia diagnoses and subtypes were identified using International Classification of Diseases 9/10 codes. Baseline prevalence was compared across revascularization strategies: percutaneous coronary intervention, coronary artery bypass grafting, or no revascularization.

RESULTS: Among 26,749 patients with ACS, the mean age was 76.7 ± 8.0 years; patients not revascularized were older than those who were (77.7 ± 8.3 vs 74.9 ± 7.0 years; P < .001). Overall, 57.4% were male, with a higher proportion among revascularized patients. The overall baseline prevalence of dementia was 5.9%, substantially lower among revascularized (1.9%) vs nonrevascularized patients (7.9%; P < .001). Dementia prevalence was 2.0% for percutaneous coronary intervention, 0.6% for coronary artery bypass grafting, and 7.9% for no revascularization. Alzheimer's disease was the most common subtype (85.7%), followed by vascular (5.7%), Lewy body/Parkinson's (3.7%), frontotemporal (1.0%), and unspecified types (3.9%).

CONCLUSION: One in 17 older adults hospitalized with ACS had a documented diagnosis of dementia at baseline, with substantial variation by revascularization strategy. These findings highlight the baseline burden of dementia in this high-risk population and support the need for future research on the incidence and progression of cognitive impairment after ACS.},
}

@article {pmid41804520,
year = {2026},
author = {Tagai, K and Tokuda, T},
title = {[Potential of Blood Biomarkers for Early Diagnosis of Dementia].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {3},
pages = {271-275},
doi = {10.11477/mf.188160960780030271},
pmid = {41804520},
issn = {1881-6096},
mesh = {Humans ; *Biomarkers/blood ; Early Diagnosis ; *Dementia/diagnosis/blood ; tau Proteins/blood ; Alzheimer Disease/diagnosis/blood ; },
abstract = {Blood biomarkers represent a major breakthrough in the early diagnosis of Alzheimer's disease (AD). Plasma p-tau217/Aβ42 ratio demonstrates diagnostic accuracy comparable to PET and CSF examinations, leading to FDA approval of the first blood-based AD test in May 2025. With insurance coverage now extending to disease-modifying therapies such as lecanemab and donanemab at the mild cognitive impairment (MCI) stage, the clinical adoption of these minimally invasive diagnostic tools is rapidly advancing. Current development includes Core 1 biomarkers (A: Aβ proteinopathy, T1: phosphorylated tau) and emerging Core 2 biomarkers (T2: tau proteinopathy), with novel assays such as mid-p-tau181 showing promise. However, its application to asymptomatic individuals in brain dock settings remains challenging due to ethical considerations, including psychological burden and the uncertainty of predicting disease progression. Future directions include integrating digital biomarkers to enhance diagnostic accuracy and generating evidence for long-term healthcare benefits, while addressing standardization across manufacturers and implementing dual-cutoff strategies to optimize clinical utility.},
}

Humans
*Biomarkers/blood
Early Diagnosis
*Dementia/diagnosis/blood
tau Proteins/blood
Alzheimer Disease/diagnosis/blood

@article {pmid41804516,
year = {2026},
author = {Tomimoto, H},
title = {[Bridging Early Detection and Intervention in Dementia].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {3},
pages = {249-253},
doi = {10.11477/mf.188160960780030249},
pmid = {41804516},
issn = {1881-6096},
mesh = {Humans ; Early Diagnosis ; *Dementia/diagnosis/therapy ; Biomarkers/blood ; Alzheimer Disease/diagnosis ; },
abstract = {Recent progress of highly sensitive detection methods including digital cognitive test and AI-assisted imaging have increasingly innovated early detection of Alzheimer's disease. Moreover, blood biomarkers such as p-tau217 and MTBR-tau243, biomarkers for amyloid and p-tau in the brain, respectively, have gained a similar sensitivity and specificity to PET study. Therefore, it is highly recommended to establish an appropriate method for bridging early detection and intervention of Alzheimer's disease, using brain dock.},
}

Humans
Early Diagnosis
*Dementia/diagnosis/therapy
Biomarkers/blood
Alzheimer Disease/diagnosis

@article {pmid41804511,
year = {2026},
author = {Nakajima, M and Kawamura, K and Akiba, C and Miyajima, M},
title = {[Pathophysiology and Diagnosis of Idiopathic Normal Pressure Hydrocephalus (Hakim's Disease)].},
journal = {Brain and nerve = Shinkei kenkyu no shinpo},
volume = {78},
number = {3},
pages = {221-225},
doi = {10.11477/mf.188160960780030221},
pmid = {41804511},
issn = {1881-6096},
mesh = {Humans ; *Hydrocephalus, Normal Pressure/diagnosis/physiopathology ; Biomarkers/blood ; },
abstract = {Idiopathic normal-pressure hydrocephalus (iNPH) is a disease that can be detected early and treated promptly through neurological screening evaluations and brain imaging. Diagnosis is established based on characteristic clinical and imaging findings demonstrating not only ventricular enlargement but also tight high cortical subarachnoid spaces, along with enlargement of the Sylvian fissures and basal cisterns. Additionally, iNPH frequently coexists with neurodegenerative disorders such as Alzheimer's disease and dementia with Lewy bodies, suggesting that the iNPH brain environment is prone to abnormal protein accumulation. Recent advances in blood-based biomarker technology have enabled the detection of amyloid-β pathology in peripheral blood samples. Therefore, in the near future, the combined use of imaging studies and blood biomarker testing in neurodegenerative disease screening may support a more comprehensive diagnosis of iNPH, including its associated neurodegenerative comorbidities.},
}

Humans
*Hydrocephalus, Normal Pressure/diagnosis/physiopathology
Biomarkers/blood

@article {pmid41804324,
year = {2026},
author = {Ardayfio, P and Mullins, GR and Khanna, R and Zimmer, JA and Wang, H and Nery, ESM and Evans, CD and Piela, P and Battioui, C and Lauzon, S and Anglin, G and Ng, HW and Jayaraman, AR and Agada, N and Natalie, CR and Brooks, DA and Sims, JR},
title = {Infusion-related reactions in donanemab-treated participants with early symptomatic Alzheimer's disease.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {1},
pages = {e70229},
pmid = {41804324},
issn = {2352-8737},
abstract = {INTRODUCTION: Infusion-related reactions (IRRs) and hypersensitivity are adverse events associated with therapeutic antibodies. Characterization of IRRs can lead to improved risk anticipation and management of this event. This post hoc analysis characterizes IRRs in donanemab-treated participants with early symptomatic Alzheimer's disease (AD) from several multicenter studies.

METHODS: Data were pooled from the donanemab-treated population from TRAILBLAZER-ALZ, TRAILBLAZER-ALZ 2, a stand-alone open-label addendum to TRAILBLAZER-ALZ 2, TRAILBLAZER-EXT, and TRAILBLAZER-ALZ 4. Descriptive statistics were used to characterize IRRs and related events. A random forest model identified potential association between IRRs and 40 baseline variables.

RESULTS: Of 2727 donanemab-treated participants, 225 (8.3%) reported IRRs. Of 216 participants with immediate events, 122 (56.5%) were mild and 83 (38.4%) were moderate. Thirteen (0.5%) participants reported a serious event. Of IRRs occurring on the day of infusion, 87.8% occurred during or within 30 min after infusion. Of donanemab-treated participants with IRRs, 194 (77.0%) reported their first IRR by the fourth infusion. The most common symptoms reported within 24 h of infusion were nausea/vomiting (3.5%), chills (3.3%), and erythema (3.1%). In an exploratory analysis, 11/29 (37.9%) participants with at least one laboratory value taken after IRR and related events, as well as a corresponding baseline value, had elevated tryptase levels after IRR; events were of moderate severity in 82% of these participants versus 44% of those without tryptase elevations. Of donanemab-treated participants who previously experienced an IRR, 164 (65.1%) received a rechallenge infusion. Prophylaxis medication (primarily antihistamines) was used at rechallenge in 38 (23.2%) of rechallenged participants but did not reduce IRR risk. Machine learning models identified previous drug allergy and previous anaphylaxis as significant predictors of IRRs (p < 0.01 for both).

DISCUSSION: IRRs are a common occurrence with donanemab treatment. The majority of IRRs among donanemab-treated participants were mild to moderate, and rechallenge was often tolerated. Serious IRRs and anaphylaxis were reported.Trial Registration: NCT03367403; NCT04437511, NCT04640077, NCT05108922.},
}

@article {pmid41804298,
year = {2026},
author = {Kang, S and Kadia, A and Wang, J and Ingram, R and Tidball, P and Jin, F and Abbasian, A and Georgiou, J and Collingridge, GL},
title = {The LOAD2 mouse model of late-onset alzheimer's disease exhibits an accelerated onset of locomotor and anxiety deficits.},
journal = {Brain and neuroscience advances},
volume = {10},
number = {},
pages = {23982128261430392},
pmid = {41804298},
issn = {2398-2128},
abstract = {Late-onset alzheimer's disease is the most common form of dementia, and it arises from complex genetic and environmental interactions. Preclinical models that replicate the slow progression and long prodromal phase of late-onset alzheimer's disease are critical for identifying early therapeutic targets. The LOAD2 mouse model, developed on the C57BL/6J genetic background, integrates key late-onset alzheimer's disease genetic risk factors: APOE4, Trem2*R47H, and an App allele encoding humanised amyloid beta. This study aimed to characterise key disease-relevant phenotypes of LOAD2 mice during ageing. Behavioural assays were conducted on 18- and 24-month-old LOAD2 and age-matched C57BL/6J wild-type control mice. At 18 months, LOAD2 mice exhibited significantly reduced locomotor activity compared to wild-type controls. However, this difference was diminished at 24 months as wild-type mice displayed an age-related decline in total distance travelled. Similarly, anxiety-like behaviour was elevated in 18-month-old LOAD2 mice relative to wild-type controls, but this difference was no longer evident at 24 months due to increased anxiety levels in aged wild-type mice. In contrast, spatial working memory and associative fear learning were intact in both LOAD2 and wild-type mice at 18 and 24 months of age, indicating no age- or genotype-dependent deficits in these forms of memory. Both groups of mice performed equally poorly in novel object and novel location recognition tasks at both ages. Thus, compared to age-matched wild-type mice, LOAD2 mice exhibit early locomotor deficits and heightened anxiety, but not overt cognitive impairment beyond that of normal ageing. These phenotypes are reminiscent of prodromal symptoms of late-onset alzheimer's disease in humans.},
}

@article {pmid41804255,
year = {2026},
author = {Marcotte, S and Levine, T and Freeman, R and Gibbons, CH},
title = {The Syn-sleep trial protocol: detection of cutaneous phosphorylated alpha-synuclein in REM sleep behavior disorder.},
journal = {Biomarkers in medicine},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/17520363.2026.2641474},
pmid = {41804255},
issn = {1752-0371},
abstract = {BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal neurodegenerative disease of misfolded alpha-synuclein (P-SYN) with a high risk of phenoconversion to a clinically apparent synucleinopathy (including Parkinson's disease, multiple system atrophy, or dementia with Lewy bodies) over 15 years.

OBJECTIVES: To determine rates of cutaneous P-SYN deposition in iRBD, to quantify changes in PSYN deposition over time, and to determine if P-SYN deposition patterns and amounts predict phenoconversion to a specific type of synucleinopathy.

CLINICAL TRIAL PROTOCOL: In a prospective, blinded study we will recruit 80 individuals with polysomnography confirmed iRBD or probable RBD using standard diagnostic criteria. Skin biopsies with dual immunohistochemical immunostaining for nerve fibers (protein gene product 9.5) and P-SYN will be completed at 3 sites using standard methodology. Quantitative measures of P-SYN and nerve fiber density will be measured blinded to any clinical data and will be followed longitudinally to determine the final clinical diagnosis.

DISCUSSION: Patients with iRBD are an important population to study due to the high rates of phenoconversion to clinically apparent synucleinopathy. Defining the frequency of P-SYN deposition and the risk of phenoconversion will aid in the development of future clinical trials that seek to alter the natural history of synucleinopathies.},
}

@article {pmid41803975,
year = {2026},
author = {Bohn, L and Vandenberg, P and Fah, H and Rajah, MN and Einstein, G and Dixon, RA},
title = {Evaluating sex and gender as separate and interactive predictors of memory aging trajectory classes: an integrative data-driven approach.},
journal = {Biology of sex differences},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13293-026-00864-2},
pmid = {41803975},
issn = {2042-6410},
support = {#G2020000063//Alberta Innovates/ ; 163902/CAPMC/CIHR/Canada ; AG008235/AG/NIA NIH HHS/United States ; },
abstract = {BACKGROUND: A priority in aging and dementia research is to integrate sex (biological attribute) and gender (sociocultural/behavioural characteristics) in theories, designs, analyses, and intervention protocols. We recently reported a data-mining procedure for operationalizing empirically-derived composite gender variables in archival databases. The present study extends the prior cross-sectional approach by examining sex and gender as separate and interactive predictors of longitudinal data-driven memory trajectory classes.

METHODS: Participants (N = 746) contributed baseline data for binary sex (female/male), education (years), and empirically-derived composite variables representing complementary gender facets. These facets included Manual Tasks and Physical Activities; Social and Household Management; Leisure, Socializing, and Travel; Cognitive Activity and Brain Games; Health Perceptions and Practices; and Subjective Memory Beliefs. We integrated these into a longitudinal episodic memory trajectory distribution spanning 42 years (53-95) of aging. Data-driven latent class growth analysis (LCGA) on the trajectory distribution identified discriminable classes. Using the R3STEP approach, we separately tested sex, gender facets, and education as predictors of membership in the higher (healthier) trajectory classes relative to the lowest (benchmark) class. We then included interaction terms to test for sex moderation of gender effects. Finally, we identified all genotyped participants and tested whether sex and gender effects were moderated by Apolipoprotein E (APOE).

RESULTS: LCGA revealed three memory classes: High-Stable (highest level/relatively stable), Moderate/Normal-Declining (average level/moderate decline), and Low-Declining (lowest level/steepest decline). Several variables separately predicted High-Stable membership. For sex, females were more likely than males to belong to this class. For gender, (a) higher scores for Social and Household Management, Cognitive Activity and Brain Games, and Subjective Memory Beliefs predicted High-Stable membership; and (b) higher scores for Manual Tasks and Physical Activities and Health Perceptions and Practices decreased the likelihood of High-Stable membership (relative to Low-Declining). Moderate/Normal-Declining membership was predicted by Social and Household Management (higher). For education, more years predicted High-Stable membership. Moderation analyses indicated that gender effects were consistent across both sexes and APOE carrier status.

CONCLUSIONS: Data-driven analyses show that biological sex and measurable facets of gender differentially contribute to memory trajectory patterns over a 42-year span of cognitively unimpaired aging.},
}

@article {pmid41803942,
year = {2026},
author = {Mueller, A and Jovalekic, A and Chapleau, M and Seidel, J and Ritter, M and Bickel, EM and Kiessling, N and MacSweeney, E and Stephens, AW and Koglin, N},
title = {In-vitro interaction studies between the amyloid PET tracer florbetaben and the amyloid-beta targeting antibodies lecanemab and donanemab on AD brain samples reveal no interferences.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {41803942},
issn = {1758-9193},
}

@article {pmid41803852,
year = {2026},
author = {Peng, X and Ouyang, C and Ma, F and Liu, Y and Luo, L and Xing, J and Feng, S and Li, L and Zhang, J and Wang, J and Cheng, H and Zhang, T and Chen, F and Wang, Y and Cui, L},
title = {De-2-hydroxyisobutyrylation of clusterin modulates neuropathology and memory deficits in an Alzheimer's disease mouse model.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-02787-2},
pmid = {41803852},
issn = {1478-811X},
support = {82371438//National Natural Science Foundation of China/ ; 82371438//National Natural Science Foundation of China/ ; 2024B1515230001//Guangdong Basic and Applied Basic Research Foundation/ ; 2024B1515230001//Guangdong Basic and Applied Basic Research Foundation/ ; 2024KCXTD034//nnovative Team Project of General Universities in Guangdong Province/ ; 2024KCXTD034//nnovative Team Project of General Universities in Guangdong Province/ ; GCC2022001//Affiliated Hospital of Guangdong Medical University High Level talent research Launch project/ ; GCC2022001//Affiliated Hospital of Guangdong Medical University High Level talent research Launch project/ ; },
}

@article {pmid41803336,
year = {2026},
author = {Mandal, S and Aran, KR},
title = {Symbiotic in Alzheimer's disease: modulating the gut-brain axis for neuroimmune homeostasis and cognitive protection.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41803336},
issn = {1568-5608},
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder defined by progressive cognitive impairment, neuroinflammation, oxidative stress, amyloid-β (Aβ) accumulation, synaptic dysfunction, mitochondrial impairment, and tau hyperphosphorylation. The gut-brain axis (GBA) is a crucial regulatory signaling cascade that links intestinal microbiome composition with both neural health and disease through the vagus nerve. Gut dysbiosis has increasingly been implicated in AD pathogenesis by exacerbating systemic and neuroinflammatory signaling, disrupting intestinal and blood-brain barrier (BBB) structural stability, and promoting microglial activation, thereby facilitating Aβ aggregation and neurodegeneration. Preclinical studies indicate that symbiotic interventions restore microbial balance and improve gut-brain communication, contributing to neuroprotective effects. Additionally, it has been demonstrated that symbiotics can restore synaptic plasticity and cognitive resilience by suppressing pro-inflammatory cytokines, as exemplified by interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α), and by upregulating neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF). These effects are associated with normalised glial reactivity, attenuation of oxidative stress, and improved mitochondrial bioenergetics, together contributing to enhanced synaptic function, reduced neuroinflammation, and preservation of cognitive performance. This review highlights a critical assessment of the treatment potential of symbiotic interventions in modulating the GBA in AD, emphasising mechanistic insights into neurodegenerative pathways and evaluating their capacity to mitigate symptoms and delay disease progression, as supported by current preclinical evidence.},
}