@article {pmid41802971,
year = {2026},
author = {Ma, X and Zhang, M and Zheng, Y and Zhang, X and Zhang, M and Xie, Y and Xie, C and Li, H and Xia, M and Li, T and Zhang, H and Aarsland, D and Zhang, W and Tang, C and Yu, X and Wang, H},
title = {Distinct cognitive profiles differentiate dementia with lewy bodies from Alzheimer's disease.},
journal = {International psychogeriatrics},
volume = {},
number = {},
pages = {100203},
doi = {10.1016/j.inpsyc.2026.100203},
pmid = {41802971},
issn = {1741-203X},
abstract = {BACKGROUND: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) share overlapping cognitive and neuropsychiatric symptoms, complicating early differential diagnosis. This study aimed to compare multidimensional impairment patterns in AD and DLB and develop a simple, interpretable classification model based on clinical scales.

METHODS: A total of 249 participants were included: 84 patients with AD, 82 with DLB, and 83 participants with normal cognition (NC). Participants completed assessments covering global cognition, six cognitive domains, neuropsychiatric and depressive symptoms. Missing values in cognitive scales were handled using multiple imputation, and results were pooled across all imputations. Then, Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine (SVM), and Random Forest (RF) were used to identify key variables. A final set of six scales was selected to build a logistic regression model distinguishing DLB from AD. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) in the entire cohort, mild stage and dementia stage.

RESULTS: DLB patients showed greater deficits in attention, visuospatial processing, and neuropsychiatric symptoms; AD patients exhibited more pronounced memory impairment. At mild stage, DLB displayed more depressive symptoms and attention deficits but milder memory decline than AD. At dementia stage, DLB presented broader impairments in executive, visuospatial, attentional, with similar global cognition. The six-feature model achieved high diagnostic accuracy in the entire cohort (AUC=0.879, 95%CI: 0.802-0.957), mild stage (AUC=0.866, 95% CI: 0.788-0.943) and dementia stage (AUC=0.939, 95% CI: 0.839-0.999).

CONCLUSION: The study identified distinct cognitive profiles of DLB and AD, and developed a concise, clinically practical model with robust diagnostic utility across disease stages, supporting its use in outpatient and resource-limited settings.},
}

@article {pmid41802492,
year = {2026},
author = {Moubarak, GA and Salama, AH and Ali, AA and Galal, AF and Fouad, SA and Eid, HM},
title = {Intranasal delivery of chitosan-coated bilosomes for repurposing Olmesartan in Alzheimer's disease therapy: Formulation, optimization, pharmacokinetic and pharmacodynamic evaluation.},
journal = {Journal of pharmaceutical sciences},
volume = {},
number = {},
pages = {104241},
doi = {10.1016/j.xphs.2026.104241},
pmid = {41802492},
issn = {1520-6017},
abstract = {Alzheimer's disease (AD) is a neurological illness that progresses over time and has limited therapeutic options. This is mostly because the blood-brain barrier prevents drugs from reaching the brain efficiently. This study sought to repurpose olmesartan (OLM), an angiotensin II receptor blocker exhibiting promising neuroprotective properties, by improving its brain-targeted delivery via intranasally administered bilosomes with chitosan shell. Chitosan coated bilosomes containing olmesartan (OLM-CTS-BLS) were formulated using a Box-Behnken design to optimize key variables (lecithin, sodium deoxycholate, and chitosan concentration) for achieving minimum diameter together with maximum entrapment efficiency and zeta potential. The optimized formulation demonstrated nanosized vesicles (184.89±6.11 nm), positive surface charge (+34.07±1.72 mV), and high encapsulation (87.36%±1.07). In vitro release showed sustained OLM delivery over 12 hours. Nasal diffusion studies conducted on sheep nasal mucosa demonstrated a significant increase in flux and permeability for OLM-CTS-BLS compared to OLM suspension. Pharmacokinetic studies in rats confirmed significantly improved brain bioavailability and a 1.4 fold increase in brain/plasma AUC ratio for OLM-CTS-BLS versus conventional routes. Behavioral assessments (Y-maze, Morris Water Maze) in lipopolysaccharide-induced AD rats revealed superior cognitive improvement in OLM-CTS-BLS-treated animals. Biochemical assays showed reduced acetylcholinesterase activity and lipid peroxidation. Histopathological and immunohistochemical evaluations demonstrated reduced amyloid-β deposition and preserved neuronal architecture without nasal toxicity. Collectively, these findings underscore the potential of intranasal OLM-CTS-BLS as a safe and effective drug delivery system for repurposing OLM in AD therapy by enhancing its brain delivery and therapeutic efficacy.},
}

@article {pmid41802283,
year = {2026},
author = {Zeng, Y and Wang, L and Liu, X},
title = {BioMNEDR: mechanism-guided network embedding for drug repurposing.},
journal = {Briefings in bioinformatics},
volume = {27},
number = {2},
pages = {},
doi = {10.1093/bib/bbag101},
pmid = {41802283},
issn = {1477-4054},
support = {T2422010//National Natural Science Foundation of China/ ; 62172170//National Natural Science Foundation of China/ ; //Fundamental Research Funds for Central Universities/ ; },
mesh = {*Drug Repositioning/methods ; Humans ; *Computational Biology/methods ; Drug Discovery ; Alzheimer Disease/drug therapy/metabolism ; Algorithms ; *Software ; },
abstract = {Drug repurposing provides a cost-effective and time-efficient strategy to accelerate therapeutic discovery, yet most computational approaches fail to capture the multi-scale biomedical mechanisms underlying drug-disease associations, limiting interpretability. We introduce BioMNEDR (mechanism-guided network embedding for drug repurposing) that integrates heterogeneous biomedical networks through biologically curated meta-paths. BioMNEDR generates low-dimensional embeddings preserving protein-protein interactions and functional hierarchies. It further integrates multi-path predictions through an XGBoost classifier. The framework achieves state-of-the-art performance, consistently surpassing strong baselines across AUROC, AUPR, recall, and F1-score, while maintaining a balanced trade-off in precision. Case studies further highlight its practical utility, demonstrating the ability to rediscover approved drugs and prioritize promising candidates, such as cromoglicic acid for Alzheimer's disease. By explicitly modeling multi-scale mechanisms, BioMNEDR enhances both predictive accuracy and biomedical interpretability, offering a robust computational framework for systematic drug repurposing.},
}

*Drug Repositioning/methods
Humans
*Computational Biology/methods
Drug Discovery
Alzheimer Disease/drug therapy/metabolism
Algorithms
*Software

@article {pmid41801601,
year = {2026},
author = {Anwer, R and Ullah, I and Khan, AU and Mir, MA and Bashir, N and Shah, SUA and Ayaz, M},
title = {Integrated computational, pharmacological and molecular investigations of piperitone in mitigating Alzheimer disease pathology by targeting cholinesterases, β-secretase and neuroinflammation.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41801601},
issn = {1568-5608},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder linked with oxidative imbalance, cholinergic dysfunction and neuroinflammation, necessitates developing new multitarget natural compounds with potential disease-modifying action. Piperitone was evaluated using in-silico, in-vitro and in-vivo methods. In-silico study identified the pharmacokinetic parameters (PK) and the interaction stability of piperitone with acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase. In-vivo assessment of spatial memory in scopolamine-induced rat model was identified by behavioral assays with donepezil as a reference standard. In-vitro assays identified activity of cholinesterases, oxidative stress markers, levels of antioxidants and neuroinflammatory substrates, quantified with Reverse Transcription Polymerase Chain Reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Piperitone demonstrated favorable PK properties & docking scores comparable to Donepezil, Tacrine & QUD. Molecular dynamics simulations (MDS) confirmed stable associations with catalytic residues of cholinesterases and beta-secretase. Dose dependent reduction was recorded in cholinesterases, improvement in behavioral outcomes, and supplemented defenses of antioxidants including Glutathione (Reduced Form (GSH), Glutathione S-Transferase (GST), Catalase (CAT), Superoxide Dismutase (SOD), and diminished Lipid Peroxidation (LPO), Nitric Oxide (NO), Tumor Necrosis Factor-alpha (TNF-α), Interleukin (IL)-1β, IL-18, Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like Receptor Family Pyrin Domain Containing 3 (NLRP3) and amyloid-β production, while improving Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Piperitone showed significant neuroprotective and cognitive enhancement benefits by modulating cholinergic signaling, oxidative stress, and neuroinflammation. These multitarget actions advocate piperitone as a prospective lead candidate for the development of disease modifying treatments for AD.},
}

@article {pmid41801600,
year = {2026},
author = {Ali, W and Choe, K and Nasir, T and Atiq, U and Tahir, M and Ahmad, W and Park, HY and Park, TJ and Kim, MO},
title = {Atraric acid mitigates the cognitive and pathological deficits in mice via Aβ1-42 induced Alzheimer's disease.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41801600},
issn = {1568-5608},
support = {RS-2025-00560253//National Research Foundation of Korea/ ; },
}

@article {pmid41801555,
year = {2026},
author = {Mehak, M and Shafee, WF and Shafee, MH and Ahmad, B},
title = {Comment on "Validity study of the Turkish version of the Mini-Addenbrooke's cognitive examination in mild cognitive impairment and Alzheimer's disease".},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {41801555},
issn = {2240-2993},
}

@article {pmid41801479,
year = {2026},
author = {Zou, H and Liu, H and Yan, F},
title = {EENet-RLA: An Explainable Prediction Learning Framework for Alzheimer's Disease Classification from EEG Signals.},
journal = {Brain topography},
volume = {39},
number = {3},
pages = {},
pmid = {41801479},
issn = {1573-6792},
support = {12062027//National Natural Science Foundation of China/ ; 202405AS350003//Cross-integration Innovation team of modern Applied Mathematics and Life Sciences in Yunnan Province/ ; GREKF22-12//Open Project of State Key Laboratory of Genetic Resources and Evolution/ ; },
mesh = {*Alzheimer Disease/physiopathology/diagnosis/classification ; Humans ; *Electroencephalography/methods ; *Deep Learning ; *Brain/physiopathology ; Signal Processing, Computer-Assisted ; Male ; },
abstract = {Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting millions worldwide. Electroencephalography (EEG), a non-invasive, cost-effective, and safe diagnostic tool, is widely used for detecting neurological conditions. Existing EEG-based classification methods for AD diagnosis have limitations, particularly in adequately considering causal relationships between channels and implementing optimal feature selection, creating a need for highly interpretable feature screening mechanisms. This study presents EENet-RLA, a framework that integrates dynamical system theory with deep learning for AD classification, validated on the BrainLat EEG dataset. The framework operates in two stages, feature extraction and EEG classification, with the deep learning architecture serving primarily as a feature mapping and representation extractor. The core methodological contribution lies in the causal, stability-driven EEG channel selection strategy based on embedding entropy (EE), which quantifies nonlinear directional interactions between EEG channels. This strategy combines bootstrap resampling, multiple random seeds, and minimum connectivity thresholds to identify reproducible, informative channels under limited sample conditions. For classification, spatial and temporal EEG features are extracted using ResNet and LSTM respectively, then fused via a Multi-Head Attention mechanism to capture discriminative patterns. The proposed approach achieves 98.54% segment-level classification accuracy and perfect individual-level performance, demonstrating the discriminative potential of causality-informed feature selection in small-sample settings. While ensuring high accuracy, the method streamlines the analytical process and demonstrates the feasibility of causal-based EEG channel selection in AD characterization, with potential applicability to studying other neurological conditions with similar signal characteristics.},
}

*Alzheimer Disease/physiopathology/diagnosis/classification
Humans
*Electroencephalography/methods
*Deep Learning
*Brain/physiopathology
Signal Processing, Computer-Assisted
Male

@article {pmid41801397,
year = {2026},
author = {Tasnim, A and Lehrner, J},
title = {Single odor identification in subjective cognitive decline, mild cognitive impairment and Alzheimer's dementia.},
journal = {Wiener klinische Wochenschrift},
volume = {},
number = {},
pages = {},
doi = {10.1007/s00508-026-02721-z},
pmid = {41801397},
issn = {1613-7671},
abstract = {BACKGROUND: Olfactory dysfunction is an early biomarker of Alzheimer's dementia (AD) and cognitive impairments. This study examines odor-specific olfactory deficits across cognitive impairment stages using the Sniffin' Sticks Odor Identification Test (SS-OIT).

OBJECTIVE: To assess the discriminative validity of specific odors in differentiating subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), amnestic mild cognitive impairment (aMCI), and AD from healthy controls (HC). Additionally, the influences of age, gender, verbal intelligence and depression on olfactory performance were analyzed. Participants were also grouped into an AD versus non-AD category (comprising SCD, naMCI, and aMCI) for logistic regression analyses.

METHODS: A retrospective analysis at the Department of Neurology of the Medical University of Vienna included 737 participants aged 50 years and older. Olfactory identification was assessed using the 16-item Sniffin' Sticks odor identification test. The discriminative power of specific odors was evaluated for distinguishing AD from non-AD groups. Bonferroni corrections were applied to adjust for multiple comparisons, which increases the stringency of statistical significance across the 16 odors tested.

RESULTS: Significant differences in odor identification were observed across diagnostic groups. The AD patients exhibited the most pronounced deficits, particularly in recognizing clove, rose and aniseed. Age negatively correlated with olfactory performance, while higher verbal intelligence was a protective factor. Key odors differentiated AD from non-AD groups, highlighting the diagnostic potential of olfactory testing.

CONCLUSION: Odor-specific olfactory deficits serve as early indicators of cognitive decline. The Sniffin' Sticks test, particularly key odors, may aid early detection and differentiation of cognitive impairments. Accounting for covariates enhances the diagnostic accuracy. Future research should aim to refine olfactory testing protocols and assess their clinical utility in broader populations.},
}

@article {pmid41801297,
year = {2026},
author = {Sekiguchi, M and Horiuchi, M and Shinoda, S and Yamanaka, J and Tozawa, Y and Higashimura, Y and Miyamae, Y and Shigemori, H},
title = {New meroterpenoids from Sargassum macrocarpum as inhibitors of amyloid β aggregation.},
journal = {Journal of natural medicines},
volume = {},
number = {},
pages = {},
pmid = {41801297},
issn = {1861-0293},
support = {22K06664//Japan Society for the Promotion of Science/ ; },
}

@article {pmid41801093,
year = {2026},
author = {Neugroschl, J and Sewell, M and Zhu, C and Dauray, A and Melnick, J and Pomerantz, E and Ryan, C and Slattery, S and Loizos, M and Meuser, C and Evans, K and Pun, K and Sano, M},
title = {Reporting of high-risk groups in research in U.S. dementia clinical trials: A systematic review.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261421224},
doi = {10.1177/13872877261421224},
pmid = {41801093},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease and related dementias (AD/ADRD) disproportionately affect Black and Hispanic populations in the U.S. Despite higher prevalence, they remain underrepresented in randomized controlled trials (RCTs). Adequate reporting and representation are essential for understanding disease biology, risk, and treatment response.ObjectiveThis systematic review examined U.S.-based AD/ADRD RCTs published from 2010-2023 to determine: (1) whether reporting of race and ethnicity has improved, (2) whether reporting is associated with study characteristics, and (3) whether reporting corresponds to greater representation of high-risk populations.MethodsFollowing PRISMA guidelines, we searched MEDLINE and Embase for RCTs of pharmacologic, nutraceutical, or procedural interventions in AD/ADRD. Trials were eligible if conducted exclusively in the U.S. between 2010 and 2023. 5428 records were screened and 126 met inclusion criteria. Data extracted included study design, size, funding source, trial phase, and reporting of race/ethnicity.ResultsOf 126 trials, 35.7% did not report race or ethnicity. Among the 64.3% that did, reporting formats varied: 19% reported race and ethnicity separately, 18.3% combined them, 14.3% provided unclear classifications, and 12.7% reported only percent White. Across reporting trials, White participants comprised 71.2-93.3% of samples; minority representation was low. Larger, multi-site, pharmacologic, and industry-funded studies were significantly more likely to report race and ethnicity (p < 0.05). No significant improvement in reporting was observed over time.ConclusionsRace and ethnicity remain inconsistently reported in AD/ADRD RCTs, and minority representation is low. Standardized reporting and inclusive recruitment strategies are needed to ensure equitable evidence for dementia treatment and prevention.},
}

@article {pmid41800907,
year = {2026},
author = {Zhang, Q and Tang, YH and Tang, XQ},
title = {Physiology of the kynurenine pathway and its implications in CNS disorders.},
journal = {Reviews in the neurosciences},
volume = {},
number = {},
pages = {},
pmid = {41800907},
issn = {2191-0200},
abstract = {The kynurenine pathway (KP), a crucial route of tryptophan (TRP) catabolism, has emerged as a focal point of investigation because of its complex involvement in regulating central nervous system (CNS) function. This metabolic pathway, which operates in various cell types within the CNS, closely links immune responses, neurotransmission, and neuroinflammation. This review provides an in-depth exploration of the KP, delineating its enzymatic constituents, metabolite profiles, and multifarious roles in sustaining CNS homeostasis, with potential implications for neuropathological conditions including Alzheimer's disease (AD), Parkinson's disease (PD), major depressive disorder (MDD), and schizophrenia (SCZ). In addition to the roles of the KP in the pathogenesis of the abovementioned diseases, the related advancements in treatment are discussed.},
}

@article {pmid41800890,
year = {2026},
author = {Chen, T and Ahmed, RM and Piguet, O and Irish, M},
title = {Behavioural rigidity as a transdiagnostic marker of nucleus accumbens dysfunction in dementia.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag095},
pmid = {41800890},
issn = {1460-2156},
abstract = {Behavioural rigidity, the tendency to persist with inflexible patterns of thoughts or actions, is increasingly recognised as a transdiagnostic symptom across psychiatric, neurodevelopmental, and neurodegenerative disorders. Empirical studies exploring the prevalence and underlying neural mechanisms of behavioural rigidity in dementia, however, are lacking. This cross-sectional study sought to delineate the structural and functional neural correlates of behavioural rigidity using a transdiagnostic approach looking across the frontotemporal lobar degeneration (FTLD) spectrum and Alzheimer's disease. A total of 204 participants were recruited, including 110 frontotemporal dementia (FTD), 53 Alzheimer's disease (AD), and 41 healthy older control participants. Within the FTD group, 66 cases were diagnosed with clinically probable behavioural variant FTD (bvFTD), 26 presented with semantic dementia (SD), and 18 cases had progressive non-fluent aphasia (PNFA). Behavioural rigidity was assessed using the Stereotypical and Motor Behaviour subscale of the Cambridge Behavioural Inventory-Revised. Voxel-based morphometry (VBM) was performed to identify grey matter regions associated with behavioural rigidity transdiagnostically, the results of which informed subsequent seed-based voxel-wise functional connectivity analyses. All imaging analyses were adjusted for relevant demographic and technical covariates. Statistical thresholds were set at voxel-level p < 0.001 (uncorrected) and cluster-level p < 0.05 (FDR-corrected). Our main finding was that behavioural rigidity is pervasive across dementia subtypes, ranging from most pronounced in bvFTD to milder/relatively absent in PNFA, relative to Controls. Whole-brain VBM across the entire patient sample revealed a significant negative association between behavioural rigidity and grey matter intensity exclusively in the bilateral nucleus accumbens. Using the bilateral nucleus accumbens as seeds, resting-state functional connectivity analysis showed that higher levels of behavioural rigidity were associated with stronger connectivity between the left nucleus accumbens and the left supplementary motor area, paracentral lobule, and precuneus. This is the first study, to our knowledge, to examine the neural substrates of behavioural rigidity across FTLD syndromes transdiagnostically using structural and functional neuroimaging approaches. Our findings reveal a gradation of rigid and repetitive behaviours, most apparent in bvFTD, which in turn reflects pathological disruption of the nucleus accumbens. Taken together, our findings highlight the need to consider repetitive and rigid behaviours as a transdiagnostic feature in neurodegenerative disorders, and one which indexes underlying nucleus accumbens pathology. More broadly, this study underscores the importance of screening for rigid and repetitive behaviours in the clinic and identifies the nucleus accumbens as a promising neural target to ameliorate these symptoms.},
}

@article {pmid41800832,
year = {2026},
author = {Kawarabayashi, T and Nakamura, T and Takahashi, R and Ueda, T and Kinoshita, S and Uchida, C and Sugawara, T and Hashimoto, K and Ishizawa, K and Amari, M and Kasahara, H and Ikeda, Y and Takatama, M and Shoji, M},
title = {Clinical Validation of Plasma p-217tau in Neurological Diseases.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70359},
pmid = {41800832},
issn = {2328-9503},
support = {18K07385//Grants for Scientific Research (C) from the Ministry of Education, Science, and Culture of Japan/ ; 22K07511//Grants for Scientific Research (C) from the Ministry of Education, Science, and Culture of Japan/ ; },
abstract = {OBJECTIVE: Plasma p-217tau is a minimally invasive but specific biomarker for diagnosing Alzheimer's disease (AD). However, its disease specificity remains to be clinically evaluated. We validated the reliability of the p-217tau biomarker in 12 other neurological diseases.

METHODS: Plasma p-217tau levels were measured in 298 participants, consisting of 81 AD patients, 204 patients with 12 other neurological diseases, and 13 healthy and cognitively unimpaired controls (HCU), using an assay system from Meso Scale Diagnostics. Cerebrospinal fluid (CSF) tau and Aß levels were simultaneously evaluated in AD, amyotrophic lateral sclerosis (ALS), and idiopathic normal pressure hydrocephalus (iNPH).

RESULTS: Plasma p-217tau levels increased in AD with the clinical stage, but also in ALS and iNPH, leading to them having decreased sensitivity and specificity for diagnosing AD. No increases in plasma p-217tau levels were seen in possible tauopathies or synucleinopathies. CSF and plasma p-217tau levels were strongly correlated in AD, but not in ALS. The plasma p-217tau/CSF p-217tau ratio was inversely higher in ALS than in AD. Active and chronic denervation potentials were associated with plasma p-217tau levels. In iNPH, plasma p-217tau was associated with cognitive dysfunction, but not with gait disturbance or urinary incontinence. CSF p-181tau, total tau, and Aß1-40 levels and the Aß1-40/1-42 ratio were reduced in iNPH.

INTERPRETATION: ALS and iNPH are two major pitfalls for the clinical application of plasma p-217tau as a biomarker of AD. Lower motor neuron injury in ALS and cognitive dysfunction in iNPH were both found to be associated with elevated plasma p-217tau levels.},
}

@article {pmid41800756,
year = {2026},
author = {Shandilya, MCV and Koutures, A and Addo-Osafo, K and Hwang, K and Vicente, M and Ewens, AN and Katz, BM and Peters, ST and Choquette, JM and Vaknalli, RN and Venkateswaran, N and Onanyan, N and Narasani, A and Ravishankar, S and Stepter, J and Western, A and Benneyworth, MA and Cohn, W and John, V and Whitelegge, JP and Vossel, K},
title = {Selective disruption of tau-SH3 interactions rescues seizure and sleep phenotypes.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag090},
pmid = {41800756},
issn = {1460-2156},
abstract = {Alzheimer's disease (AD) patients frequently experience seizures, sleep disturbances, and other forms of neural network dysfunction that accelerate cognitive decline. Although tau-lowering therapies may alleviate these features, they also risk disrupting essential physiological functions of tau, leading to motor impairments. We hypothesized that targeted mutations within tau's proline-rich domain-regions critical for binding SH3-containing proteins implicated in seizures and excitotoxicity-could selectively disrupt pathological interactions while preserving normal cognition and behaviour. To test this, we generated two tau knockin mouse lines: AxxA6, carrying proline-to-alanine mutations in the sixth PxxP motif, and R221A, containing an arginine-to-alanine substitution at residue 221. Tau-protein interactions were evaluated using proximity ligation assays in cultured hippocampal neurons and co-immunoprecipitation-mass spectrometry of cortical lysates. To model epilepsy, Kv1.1 heterozygous knockout mice were crossed with tau knockin mice. Mice underwent 24-hour cortical EEG recordings. Seizure susceptibility was assessed following intraperitoneal kainic acid (25 mg/kg). Hippocampal slice electrophysiology was used to measure epileptic bursting after picrotoxin/4-AP application. Comprehensive motor and cognitive testing were performed in AxxA6 and R221A lines at young and older ages. Both variants reduced tau's binding to the SH3-containing proteins BIN1, PLCγ1, and p85⍺/PI3K, with AxxA6 specifically decreasing Fyn interaction (P < 0.0001). Coimmunoprecipitation-mass spectrometry revealed variant-specific alterations in tau interactomes, including increased synaptotagmin-5 binding in both lines (P < 0.05). AxxA6 knockin mice displayed unique resistance to kainic-acid-induced seizures. AxxA6 knockin also reduced epileptic spike rates in Kv1.1-/- mice (P = 0.02), along with improved beta power during REM (P < 0.05), and rescued sleep disruptions (P < 0.002). Both AxxA6 and R221A prevented the increase in epileptiform bursting in Kv1.1-/- hippocampal slices after picrotoxin/4-AP (P < 0.05) and improved survival in Kv1.1-/- mice. Motor function, cognition, and body weight were preserved in both lines across ageing (3-7 and 14-18 months), in contrast to age-related weight gain and motor deficits in tau knockout mice. These findings demonstrate that precision targeting of tau's sixth PxxP motif can selectively disrupt pathological protein interactions while preserving physiological function, offering a promising therapeutic strategy to mitigate tau-driven neuronal and network dysfunction without compromising cognitive or motor health.},
}

@article {pmid41800385,
year = {2026},
author = {Ronchi, J and Foti, M},
title = {MIRit: an integrative R framework for the identification of impaired miRNA-mRNA regulatory networks in complex diseases.},
journal = {Bioinformatics advances},
volume = {6},
number = {1},
pages = {vbag042},
pmid = {41800385},
issn = {2635-0041},
abstract = {MOTIVATION: MicroRNAs (miRNAs) play a central role in controlling gene expression, and their abnormal activity is frequently linked to disease. Despite advancements in transcriptomic technologies, elucidating miRNA-mediated mechanisms remains challenging due to methodological limitations and a lack of standardized frameworks.

RESULTS: To overcome these barriers, we developed MIRit, a comprehensive R package designed for the rigorous analysis of miRNA-mRNA interactions. With flexible support for both matched and unmatched datasets, MIRit leverages cutting-edge target identification strategies and applies suitable statistical approaches for each scenario. In this study, we benchmarked the performance of commonly used statistical tests for integrative miRNA analysis and demonstrated the effectiveness of MIRit across three human disease contexts-dilated cardiomyopathy, clear cell renal cell carcinoma, and Alzheimer's disease-by uncovering functionally relevant miRNA-target disruptions consistent with known disease mechanisms. Through its streamlined pipeline and biologically appropriate methods, MIRit enables more reproducible and accurate insights into the complex landscape of post-transcriptional regulation.

The tool is fully open-source and freely accessible via Bioconductor (https://bioconductor.org/packages/release/bioc/html/MIRit.html), making it readily available to the broader scientific community.},
}

@article {pmid41800329,
year = {2026},
author = {Gonzalez, M and West, R and Tsang, A and Ocampo, O and Hudson, PK and Pecic, S},
title = {Identification of quinolinyl-containing dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors with moderate potency towards acetylcholinesterase.},
journal = {Results in chemistry},
volume = {23},
number = {},
pages = {},
pmid = {41800329},
issn = {2211-7156},
abstract = {Using a polypharmacological approach, we designed two different quinolinyl libraries by merging the pharmacophores of three targeted enzymes, fatty acid amide hydrolase (FAAH), soluble epoxide hydrolase (sEH), and acetylcholinesterase (AChE). A 5-step synthetic scheme yielded 13 various analogs that were evaluated in FAAH, sEH, and AChE biological enzymatic assays. Most analogs are active in human FAAH and human sEH but possess only moderate activity in electric eel AChE, exemplified with 9i, a 3-quinolinyl-4-nitrophenyl analog with 15.8 nM, 36.4 nM, and 2.165 μM inhibition potencies in FAAH, sEH, and AChE respectively. Docking studies of 9i revealed key interactions with FAAH and sEH but limited interactions with AChE, suggesting directions for future structural modifications that could improve potency and selectivity.},
}

@article {pmid41800328,
year = {2026},
author = {Ren, M and Chen, H and Li, Z and Zhuang, J and Yang, A and Li, X and Li, X and Wang, X and Xu, Z and Liu, X and Song, J and Jiang, T and Xu, Z and Gao, X and Zhao, Q},
title = {ZRMQ-22, a novel DYRK1A inhibitor, attenuates neuroinflammation and cognitive impairments in LPS-induced mice: a potential strategy for Alzheimer's disease.},
journal = {RSC medicinal chemistry},
volume = {},
number = {},
pages = {},
pmid = {41800328},
issn = {2632-8682},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and memory loss. Targeting the kinase DYRK1A has emerged as a promising therapeutic strategy, as it plays a critical role in multiple key AD pathologies, including tau phosphorylation, β-amyloid (Aβ) production, and the regulation of neuroinflammatory processes. In this study, a series of novel quinazoline derivatives were designed and synthesized as DYRK1A inhibitors. Through preliminary anti-neuroinflammatory screening in a lipopolysaccharide (LPS)-induced BV2 microglial cell model, ZRMQ-22 was identified as a promising candidate that targets neuroinflammatory pathways in AD. This compound exhibits potent nanomolar-range inhibitory activity against DYRK1A, with an IC50 value of 0.35 nM. In LPS-stimulated BV2 cells, ZRMQ-22 concentration-dependently inhibited nitric oxide (NO) production, showing an IC50 of approximately 1 μM. Furthermore, at a concentration of 1 μM, it significantly suppressed the secretion of pro-inflammatory cytokines TNF-α and IL-6, with inhibition rates of 64.99% and 114.35%, respectively. In vivo experiments demonstrated that ZRMQ-22 effectively reduced levels of inflammatory markers and improved cognitive function in an LPS-induced neuroinflammation mouse model using C57BL/6 mice. These findings highlight ZRMQ-22 as a potent and safe DYRK1A inhibitor with significant efficacy in alleviating neuroinflammation and cognitive impairment, supporting its further development as a therapeutic candidate for AD.},
}

@article {pmid41800250,
year = {2026},
author = {Yen, YH and Yuan, F and Tang, D and Luo, JF and Ming, C and Kang, PJ and Su, H and Chong, CM and Zhang, SC},
title = {APP Deficiency Ameliorates FAD Presenilin 1 F105C and A246E Mutations-induced Mitochondrial Dysfunction in Human Cortical Neurons.},
journal = {International journal of biological sciences},
volume = {22},
number = {5},
pages = {2720-2735},
pmid = {41800250},
issn = {1449-2288},
mesh = {Humans ; *Presenilin-1/genetics/metabolism ; *Neurons/metabolism ; *Amyloid beta-Protein Precursor/genetics/metabolism/deficiency ; *Mitochondria/metabolism/genetics ; Induced Pluripotent Stem Cells/metabolism ; Mutation/genetics ; *Alzheimer Disease/metabolism/genetics ; Cerebral Cortex/metabolism ; },
abstract = {BACKGROUND: Mitochondrial dysfunction is widely regarded as a central and early feature of Alzheimer's disease (AD) pathology. Prior studies suggest that the accumulation of amyloid precursor protein (APP) within mitochondria contributes to this dysfunction. Mutations in presenilin-1 (PS1), which account for most cases of early-onset familial AD (FAD), have also been shown to impair mitochondrial function. In this study, we investigated how APP influences PS1 mutation-induced mitochondrial dysfunction in human cortical neurons derived from patient induced pluripotent stem cells (iPSCs).

METHODS: We analyzed transcriptomic and proteomic datasets from postmortem sporadic AD cortex to identify key dysregulated pathways. To functionally interrogate selected mechanisms, we established a panel of CRISPR/Cas9-engineered human iPSC lines, including PS1 mutant lines (PS1[+/F105C] and PS1[+/A246E]), an APP knockout derivative (APP[-/-]_PS1[+/F105C]), and their isogenic wild-type controls. These iPSCs were differentiated into cortical neurons for functional studies. Following directed differentiation into cortical neurons, biochemical analyses and super-resolution imaging were conducted to evaluate mitochondrial and neuronal phenotypes.

RESULTS: Analyses of sporadic AD cortical transcriptomes and proteomes identified mitochondrial dysfunction as a prominently altered pathway. In agreement, cortical neurons differentiated from FAD PS1 mutant (F105C and A246E) iPSCs displayed mitochondrial defects and AD-related phenotypes, both of which were mitigated by APP knockout.

CONCLUSIONS: These findings provide critical insights into the bridging role of APP in FAD PS1 mutant-mediated mitochondrial dysfunction, advancing our understanding of the cellular mechanisms underlying AD.},
}

Humans
*Presenilin-1/genetics/metabolism
*Neurons/metabolism
*Amyloid beta-Protein Precursor/genetics/metabolism/deficiency
*Mitochondria/metabolism/genetics
Induced Pluripotent Stem Cells/metabolism
Mutation/genetics
*Alzheimer Disease/metabolism/genetics
Cerebral Cortex/metabolism

@article {pmid41800101,
year = {2026},
author = {Costachescu, I and Gogu, RM and Stanciu, GD and Solcan, C and Horodincu, L and Szilagyi, A and Craciun, VC and Ababei, DC and Tamba, BI},
title = {Therapeutic relevance of an EU-GMP certified Cannabis sativa L. strain in a dual in vivo model of cognitive impairment and chronic neuropathic pain.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1761426},
pmid = {41800101},
issn = {1663-9812},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and frequently co-occurs with chronic pain. Worldwide, over 55 million people are affected by AD, with nearly half experiencing persistent pain. Chronic pain has been linked to accelerated memory deterioration and an increased risk of dementia, but the interplay between these conditions remains poorly understood. Existing therapies for AD and chronic pain are limited in efficacy, highlighting the need for interventions targeting multiple pathological pathways. The endocannabinoid system, which is altered in both AD and chronic pain, represents a potential therapeutic target, though its role in AD patients with comorbid pain remains unexplored.

METHODS: The study evaluated the effects of an EU-GMP certified Cannabis sativa L. strain (5 mg/kg, Cannabixir® Medium Flos) on neurobiological alterations in a rat model designed to explore mechanistic interactions between scopolamine-induced transient cognitive impairment and chronic neuropathic pain induced by unilateral sciatic nerve ligation. Treatment outcomes were assessed through nociceptive tests, clinical monitoring and tissue analyses to examine cognitive and pain-related effects.

RESULTS: Cannabixir® Medium Flos induced robust, time-dependent analgesia in thermal nociceptive tests, with the combination of the Cannabis sativa L. strain, donepezil and tramadol producing significantly longer response latencies than tramadol alone. Mechanical sensitivity was minimally affected across treatments. Immunohistochemical analyses revealed that Cannabixir® Medium Flos, either alone or in combination with donepezil or tramadol, produced the most pronounced neuroprotective effects, reducing astrocytic (GFAP) and microglial (Iba1) activation, lowering Caspase-3 and IL-6 expression, and preserving both hippocampal neuronal integrity as well as peripheral nerve structure.

CONCLUSION: These findings indicate that Cannabixir® Medium Flos, particularly when combined with donepezil and tramadol, provides superior analgesic and neuroprotective effects compared to tramadol alone. Its multi-target action - alleviating thermal nociception, reducing neuroinflammation, limiting apoptosis and preserving neuronal and peripheral nerve integrity-supports its potential as an adjunct therapy in managing dementia with comorbid chronic neuropathic pain. Future studies should explore the molecular mechanisms underlying these effects and assess long-term safety and efficacy across diverse models of neurodegeneration and chronic pain.},
}

@article {pmid41799935,
year = {2026},
author = {Zhou, Q and Sun, F and Zhang, Y and Cao, X and Li, M and Yu, H and Jiang, T and Li, S and Wang, W and Xie, J and He, T and Liu, Y and Liu, X and Yang, Y and Ke, D and Wang, XC and Liu, E and Wang, JZ},
title = {Downregulating Platelet Endothelial Cell Adhesion Molecule-1 Enhances Learning and Memory and Alleviates Hallmark Pathologies in Alzheimer's Disease.},
journal = {MedComm},
volume = {7},
number = {3},
pages = {e70665},
pmid = {41799935},
issn = {2688-2663},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder that currently lacks cures; thus, searching for new biomarkers and unraveling its underlying mechanisms are crucial for devising effective therapies. Here, we discovered that both mRNA and protein levels of CD31 (platelet endothelial cell adhesion molecule-1, PECAM1), a transmembrane glycoprotein in immunoglobulin superfamily, were significantly higher in the brains of AD individuals and different AD transgenic mice, and the elevated CD31 was related to the recognized AD pathologies. Additional studies demonstrated that systemically knockdown of CD31 in 5xFAD mice significantly improved the cognitive functions with decreased AD hallmark pathologies, including β-amyloid precipitation and tau hyperphosphorylation. Moreover, CD31 knockdown alleviated neuroinflammation, evidenced by the diminished microglial stimulation and suppressed expression of pro-inflammatory cytokines. Transcriptomic analysis indicated considerable changes in the AD-involved gene expression in 5xFAD mice, and CD31 knockdown rectified imbalanced gene expression. Mechanistically, we further revealed that CD31 knockdown suppressed the expression of STAT1 and IRF1 by reducing histone lactylation at H3K14 and H4K12, thereby modulating the transcriptional programs driving neuroinflammation and AD pathology. These findings illustrate that CD31 may act as a promising target for creating novel therapeutic strategies.},
}

@article {pmid41799888,
year = {2026},
author = {Qin, FL and He, X and Huang, XL and Wang, YQ and Mao, FL and Ding, KF},
title = {Association between blood neurofilament light chain levels and vascular cognitive impairment: a systematic review and meta-analysis.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1779717},
pmid = {41799888},
issn = {1662-4548},
abstract = {OBJECTIVE: Vascular cognitive impairment (VCI) is the second leading cause of cognitive impairment after Alzheimer's disease, primarily associated with vascular risk factors and cerebrovascular disease. Advances in ultra-low concentration single-molecule array (Simoa) technology have enabled the quantitative monitoring of blood neurofilament light chain (NfL) levels. Consequently, we performed a meta-analysis to evaluate the association between blood NfL levels in VCI.

METHODS: This meta-analysis was conducted in accordance with the PRISMA guidelines. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Information (VIP), and Wanfang Data databases, with a search period extending from database inception to December 3, 2025. Two reviewers independently performed the literature selection, data extraction, and assessed the study quality using the Newcastle-Ottawa Scale (NOS). The weighted mean difference (WMD) and its 95% confidence interval (CI) were used to combine effect sizes. Heterogeneity was evaluated utilizing the Chi-square (χ2) test (Cochran's Q) and the index of inconsistency (I[2]) statistic. Publication bias was evaluated by funnel plots and Egger's regression analysis.

RESULTS: This systematic review included 13 studies, comprising 3,716 patients. The meta-analysis results indicated that blood NfL levels in VCI patients were significantly higher than those in the non-VCI group (WMD = 15.06, 95% CI = [11.41, 18.71], p < 0.00001). Subgroup analysis further demonstrated that the elevated trend of NfL levels in VCI patients remained consistent across different study designs, detection methods, VCI Subtypes, countries, control group types, specimen type, and statistical adjustment (p < 0.05).

CONCLUSION: Our results suggest that blood NfL levels are significantly higher in VCI patients compared to non-VCI patients, indicating a strong association between blood NfL and VCI. This supports its potential as a discriminative biomarker for VCI.

https://www.crd.york.ac.uk/prospero/, identifier CRD420251240858.},
}

@article {pmid41799879,
year = {2026},
author = {Gourdeau, C and Gourdeau, CL and Bernier, PJ and Laforce, R},
title = {Enhanced diagnostic interpretation of the MoCA using machine learning.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1679649},
pmid = {41799879},
issn = {1662-4548},
abstract = {INTRODUCTION: Artificial Intelligence (AI) is increasingly being integrated into clinical practice to optimize diagnosis in neurocognition. By capturing distinct cognitive signatures, this approach may offer a more precise alternative to the traditional interpretation of the Montreal Cognitive Assessment (MoCA) which often relies on a fixed cutoff score (26/30). We aimed to evaluate whether machine learning models, by integrating detailed MoCA subtest scores, demographic variables, and cognitive chart-derived metrics, can improve the detection of cognitive impairment and classification of dementia subtypes.

METHODS: We analyzed 38,746 clinical observations (17,188 unique individuals) from the National Alzheimer's Coordinating Center database. Five supervised learning algorithms, Extreme Gradient Boosting (XGBoost), Random Forest, Support Vector Machine (SVM), Logistic Regression, and k-Nearest Neighbors (KNN), were trained using detailed MoCA subtest scores, demographic variables, and cognitive chart-derived metrics as predictors. To ensure generalizability of results and prevent data leakage, we applied a rigorous nested Repeated Grouped Cross-Validation strategy. Decision thresholds were optimized via the Youden Index on independent calibration sets, and model interpretability was ensured through SHAP value analysis.

RESULTS: Machine learning models consistently outperformed conventional approach. For the global detection of cognitive impairment, XGBoost achieved the best performance (Youden Index 0.61 vs. 0.54 for the standard cutoff). Regarding subtype classification, models demonstrated variable discriminative capacity depending on clinical homogeneity: primary progressive aphasia was best classified (Youden ≈ 0.77), followed by Lewy body dementia and Alzheimer's disease, while vascular dementia remained more challenging to isolate. Feature importance analysis highlighted the Cognitive Quotient as a robust universal predictor, while pinpointing disease-specific drivers such as delayed recall for Alzheimer's disease and verbal fluency for primary progressive aphasia.

CONCLUSION: Our findings suggest interpretable machine learning enhances diagnostic utility of the MoCA, yielding superior accuracy compared to a fixed cutoff. By synthesizing individualized subtest profiles within a transparent framework, this approach offers a clinically actionable solution. It transforms the MoCA from a simple screening tool to a precision diagnostic aid, optimizing patient triage in the era of disease-modifying therapies.},
}

@article {pmid41799875,
year = {2026},
author = {Timmons, F and Donlon, E and Tiernan, P},
title = {New perspectives on peer support in an online intervention for family carers of people living with dementia-evidence from an Irish NGO.},
journal = {Frontiers in dementia},
volume = {5},
number = {},
pages = {1743166},
pmid = {41799875},
issn = {2813-3919},
abstract = {INTRODUCTION: The rising prevalence of dementia globally and in Ireland has intensified the need for effective support for family carers, who provide the majority of care for people living with dementia. This study examines an established education intervention called Home Based Care-Home Based Education (HBC-HBE), an online course delivered by The Alzheimer Society of Ireland (ASI). It explores if and how participants found the course to be supportive and investigates the role and importance of peer support in this regard.

METHODS: Using a mixed-methods case study approach, the research draws on survey data (n = 225) and interviews (n = 12). Quantitative data were analyzed using descriptive statistics, while qualitative data underwent template analysis.

RESULTS: Findings indicate that overall participants found the course to be supportive. Research participants reported that peer support on the course helps reduce isolation, enhances confidence, and facilitates knowledge sharing. However, challenges were also identified, including those related to emotional readiness, group dynamics, and technology barriers.

DISCUSSION: The study finds that online peer‑supported education constitutes a valuable source of support for family carers of people living with dementia, notwithstanding certain challenges that also arise. Recommendations are offered in relation to improved course design and structure, including Moodle course usability, developing tutor facilitation skills, and introducing pre-course screening of candidates. Finally, implications in relation to national policies on dementia and digital skills are discussed.},
}

@article {pmid41799830,
year = {2025},
author = {Tangavelou, K and Bondu, V and Li, M and Li, W and Liao, FF and Bhaskar, K},
title = {The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.},
journal = {Genomic psychiatry : advancing science from genes to society},
volume = {1},
number = {6},
pages = {48-58},
pmid = {41799830},
issn = {2997-2388},
abstract = {The degradation of aggregation-prone tau is regulated by the ubiquitin-proteasome system (UPS) and autophagy, which are impaired in Alzheimer's disease (AD) and related dementias (ADRD), causing tau aggregation. Protein ubiquitination, with its linkage specificity determines the fate of proteins, which can be either protein degradative or stabilizing signals. While the linear M1-linked ubiquitination on protein aggregates serves as a signaling hub that recruits various ubiquitin-binding proteins for the coordinated actions of protein aggregate turnover and inflammatory NF-κB activation, the deubiquitinase OTULIN counteracts the M1-linked ubiquitin signaling. However, the exact role of OTULIN in neurons and tau aggregates clearance in AD are unknown. Based on our quantitative bulk RNA sequence analysis of human inducible pluripotent stem cell (iPSC)-derived neurons (iPSNs) from an individual with late-onset sporadic AD (sAD2.1), a downregulation of the ubiquitin ligase activating factors (MAGE-A2/A2B/H1) and OTULIN long non-coding RNA (OTULIN lncRNA) was observed compared to healthy control WTC11 iPSNs. The down-regulated OTULIN lncRNA is concurrently associated with increased levels of OTULIN protein and phosphorylated tau at p-S202/p-T205 (AT8), p-T231 (AT180), and p-S396/p-S404 (PHF-1) in sAD2.1 iPSNs. Inhibiting the deubiquitinase activity of OTULIN with a small molecule, UC495 reduced the phosphorylated tau in iPSNs and SH-SY5Y cells, whereas the CRISPR-Cas9-mediated OTULIN gene knockout in sAD2.1 iPSNs decreased both the total and phosphorylated tau levels. CRISPR-Cas9-mediated OTULIN knockout in SH-SY5Y resulted in a complete loss of tau at both mRNA and protein levels, and increased levels of polyubiquitinated proteins, which are being degraded by the proteasome as confirmed with an inhibitor, Lactacystin. In addition, SH-SY5Y OTULIN [KO] cells showed downregulation of various genes associated with inflammation, autophagy, ubiquitin-proteasome system, and the linear ubiquitin assembly complex (LUBAC) that consequently may prevent development of an autoinflammation in the absence of OTULIN gene in neurons. Together, our results suggest, for the first time, a non-canonical role for OTULIN in regulating the gene expression and RNA metabolism, which may have a significant pathogenic role in exacerbating tau aggregation in neurons. Thus, OTULIN could be a novel potential therapeutic target for AD and ADRD.},
}

@article {pmid41799762,
year = {2026},
author = {Ma, X and Ibrahim, AA and Ma, L and Ma, X and Ma, Z and Liu, Y and Li, D and Liu, J and Xu, X and Dong, H and Chen, X and Peng, F},
title = {Sex-Specific Prediction Models of Alzheimer's Disease: A Gene Expression Analysis.},
journal = {International journal of medical sciences},
volume = {23},
number = {3},
pages = {852-863},
pmid = {41799762},
issn = {1449-1907},
mesh = {Humans ; *Alzheimer Disease/genetics/blood/diagnosis ; Male ; Female ; Gene Expression Profiling ; Sex Factors ; Aged ; Biomarkers/blood ; Brain/metabolism/pathology ; Transcriptome ; },
abstract = {Alzheimer's disease (AD) exhibits sex-specific molecular signatures that may improve diagnostic precision. We aimed to identify and validate male- and female-specific blood and brain gene expression biomarkers for AD prediction. We analyzed four GEO datasets (blood- and brain-derived) using limma and Fisher's meta-analysis to identify sex-specific differentially expressed genes, assessed age associations via linear regression, and constructed 10-fold cross-validated logistic regression models. After performing a meta-analysis, 74 differentially expressed genes were identified in the female cohort and 89 DEGs were screened in the male cohort. ERH and MRPS33 were identified as the most relevant genes in the male cohort, and NDUFA1 and NDUFS5 were screened in the female cohort. The identified genes were downregulated in AD samples compared to controls. Both male-specific and female-specific prediction models achieved an AUC of above 0.7 in two external validation blood-derived datasets as well entorhinal cortex dataset. Paradoxically, qPCR showed significant upregulation of all four genes in the AD group compared to the control group.},
}

Humans
*Alzheimer Disease/genetics/blood/diagnosis
Male
Female
Gene Expression Profiling
Sex Factors
Aged
Biomarkers/blood
Brain/metabolism/pathology
Transcriptome

@article {pmid41799310,
year = {2026},
author = {Morrissey, S and King, S and Au-Yeung, B and Hornberger, M},
title = {Impact of a police safeguarding program on reducing dementia-related missing incidents in the United Kingdom.},
journal = {Innovation in aging},
volume = {10},
number = {3},
pages = {igaf132},
pmid = {41799310},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: People living with dementia are at increased risk of missing episodes, which can have serious safety consequences for the individual as well as increasing burden for families, emergency services, and care services. A UK police safeguarding scheme was developed in response to reduce the risk of missing incidents through proactive risk management and early intervention. This study evaluates whether the safeguarding scheme effectively reduces the risk of missing incidents for individuals taking part in the scheme.

RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using a police database of 846 individuals living with dementia taking part in the safeguarding scheme. Descriptive statistics and proportion comparisons were used to evaluate changes in missing incident characteristics before and after joining the scheme, stratified by risk level and dementia subtype.

RESULTS: We found that there were fewer missing incidents and fewer individuals with a recorded missing episode after joining the safeguarding scheme. Individuals with first missing incidents occurring after joining the scheme were found significantly faster (2.73 hours) than those with a first incident occurring before joining the scheme (5.39 hours). Among those identified as high-risk-individuals with a previous missing incident-81.21% did not go missing again after participating in the scheme. Individuals with Alzheimer's disease were more likely to go missing after taking part in the safeguarding scheme than those with vascular dementia. While individuals with a history of missing incidents remained at higher risk, the majority did not go missing again after joining the scheme.

DISCUSSION AND IMPLICATIONS: Overall, the safeguarding scheme was effective in reducing the rate of missing incidents among people with dementia. These findings promote the proactive use of police safeguarding programs and suggest that widespread implementation could improve safety and independence for people living with dementia.},
}

@article {pmid41799154,
year = {2026},
author = {Singh, AK and Kundu, TK},
title = {Landscape of Protein Post-Translational Modifications in Age-Related Neurodegenerative Disorders: Implications in Protein Aggregation, Altered Cellular Processes, and Therapeutics.},
journal = {ACS omega},
volume = {11},
number = {8},
pages = {12865-12885},
pmid = {41799154},
issn = {2470-1343},
abstract = {Accumulation of aggregated or nonfunctional proteins during the aging process is a common hallmark of degenerating neurons in various neurodegenerative disorders. Post-translational modifications (PTMs) such as acetylation, methylation, phosphorylation, and ubiquitination, etc. in combination with the protein quality control machinery such as autophagy and proteasome systems are essential for the degradation of these toxic aggregates, to maintain normal protein turnover and function of neurons. Abnormal protein quality control machinery primarily mediated by altered post-translational modifications of various proteins are linked to neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and many others. Accumulating evidence from the past two decades shows that targeting these PTMs with various small molecule activators or inhibitors restores synaptic and cognitive processes associated with these neurodegenerative diseases. Here, in this review, we highlight how these PTMs affect the accumulation and aggregation of nonfunctional proteins in various neurodegenerative diseases. Also, we highlight the current advances in exploring small molecule modulators of modifying enzymes as therapeutic options for these diseases.},
}

@article {pmid41799150,
year = {2026},
author = {Franco, DP and Caruso, L and Grillo, DCN and Nadur, NF and de Azevedo, LL and Pereira, TM and da Silva, MC and Lacerda, RB and Pinheiro, PSM and Riger, CJ and Kümmerle, AE},
title = {Synthesis and Pharmacological Evaluation of Novel 1,5-Disubstituted-3-amino-1,2,4-triazoles Designed as Multitarget Directed Ligands for Alzheimer's Disease Targets.},
journal = {ACS omega},
volume = {11},
number = {8},
pages = {13184-13198},
pmid = {41799150},
issn = {2470-1343},
abstract = {A series of 3-amino-1,2,4-triazole derivatives was synthesized and evaluated for their multitarget activities relevant to Alzheimer's disease. Inhibition assays revealed potent and preferential inhibition of acetylcholinesterase (AChE) for most of compounds, with IC50 values of up to 0.38 μM and selectivity ratios up to 32-fold over butyrylcholinesterase (BChE). Qualitative molecular dynamics indicated that interactions at the PAS and CAS appear to occur synergistically, with positive cooperativity. Electron-withdrawing groups in R1 and R2 favorize PAS interactions that seem to guide efficient CAS interactions, mainly with residue Trp86 in AChE and Trp107 in BChE. Metal-binding studies showed intrinsic complexation of Cu[2+] and Fe[3+] for the 3-amino-1,2,4-triazole compounds, which could be expanded to other metals by specific structural modifications in ortho-position of R1 substituent. Selected derivatives also demonstrated low toxicity and protective antioxidant effects in Saccharomyces cerevisiae, significantly reducing lipid peroxidation.},
}

@article {pmid41799067,
year = {2026},
author = {Isawi, IH and Al-Zoubi, R and Hajjo, R and Obeidat, RM and AlKhawaldeh, IH and Al Kilani, OM and Alhaj Hasan, MJ and Morales, P},
title = {Computational Studies toward the Identification of CB2R-M1R Dual Modulators.},
journal = {ACS omega},
volume = {11},
number = {8},
pages = {13121-13136},
pmid = {41799067},
issn = {2470-1343},
abstract = {The complex and multifactorial nature of different neurodegenerative disorders hampers the capacity to identify effective treatments. Therefore, instead of relying solely on monotherapies or combination therapies, which typically come with dosing complications and limited synergy, multitarget-directed ligand strategies have emerged as one of the most dynamic and promising approaches to improve outcomes for such diseases. This study sought to identify dual modulators that specifically target cannabinoid receptor type 2 (CB2R) and muscarinic acetylcholine receptor subtype 1 (M1R), two receptors involved in various physiological and neurological processes and frequently implicated in disorders like Alzheimer's, Parkinson's, and chronic pain. Herein, we utilized a comprehensive computational pipeline starting with a network pharmacology analysis to map the pharmacological landscape of the dual-targeted ligands. Thereafter, molecular descriptors were employed to uncover structural similarities between CB2R agonists and M1R-positive allosteric modulators. Promising candidates were further evaluated for their binding affinities to the corresponding receptors by molecular docking studies. Collectively, these integrated computational approaches yielded a shortlist of chemotypes with the potential for dual regulation of CB2R and M1R. These findings provide a computational foundation and potential chemical starting points for future experimental studies aimed at exploring CB2R-M1R dual modulation in intricate neurodegenerative disorders and related conditions.},
}

@article {pmid41799028,
year = {2026},
author = {Chen, Y and Farazi, M and Yang, Z and Fan, Y and Ashton, N and Reiman, EM and Su, Y and Wang, Y},
title = {Enhancing Alzheimer's Diagnosis: Leveraging Anatomical Landmarks in Graph Convolutional Neural Networks on Tetrahedral Meshes.},
journal = {Information processing in medical imaging : proceedings of the ... conference},
volume = {15830},
number = {},
pages = {65-78},
pmid = {41799028},
issn = {1011-2499},
abstract = {Alzheimer's disease (AD) is a major neurodegenerative condition that affects millions around the world. As one of the main biomarkers in the AD diagnosis procedure, brain amyloid positivity is typically identified by positron emission tomography (PET), which is costly and invasive. Brain structural magnetic resonance imaging (sMRI) may provide a safer and more convenient solution for the AD diagnosis. Recent advances in geometric deep learning have facilitated sMRI analysis and early diagnosis of AD. However, determining AD pathology, such as brain amyloid deposition, in preclinical stage remains challenging, as less significant morphological changes can be observed. As a result, few AD classification models are generalizable to the brain amyloid positivity classification task. Blood-based biomarkers (BBBMs), on the other hand, have recently achieved remarkable success in predicting brain amyloid positivity and identifying individuals with high risk of being brain amyloid positive. However, individuals in medium risk group still require gold standard tests such as Amyloid PET for further evaluation. Inspired by the recent success of transformer architectures, we propose a geometric deep learning model based on transformer that is both scalable and robust to variations in input volumetric mesh size. Our work introduced a novel tokenization scheme for tetrahedral meshes, incorporating anatomical landmarks generated by a pre-trained Gaussian process model. Our model achieved superior classification performance in AD classification task. In addition, we showed that the model was also generalizable to the brain amyloid positivity prediction with individuals in the medium risk class, where BM alone cannot achieve a clear classification. Our work may enrich geometric deep learning research and improve AD diagnosis accuracy without using expensive and invasive PET scans.},
}

@article {pmid41798811,
year = {2026},
author = {Wang, S and Yang, Y and Cheng, K and Yang, X and Wang, X and Liu, Y and Qiao, Y and Gao, W and Wen, Y},
title = {Clinical study on gray matter volume reduction, gait disorders, and fall risk in patients with Alzheimer's disease.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1737591},
pmid = {41798811},
issn = {1664-2295},
abstract = {OBJECTIVE: Falls represent a major threat to the physical and mental health of older adults. This study is dedicated to determining the relationships of fall risk with reduced gray matter volume and gait disorders in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).

METHODS: 24 aMCI and 21 AD patients were recruited from the Neurology Department of the Second Hospital of Hebei Medical University from January 2024 to December 2024. A prospective nested case-control design was employed on eligible participants for general data collection, neuropsychological testing, gait analysis [including single-task walking (STW) and dual-task walking (DTW)], structural MRI and following up for 6-12 months. The primary outcome was fall that occurred during the follow-up period (recorded through telephone follow-up), and the secondary outcomes were differences in baseline cognitive function, gait parameters, and brain structure between the fall group and the non-fall group. Subjects were categorized as fallers or non-fallers based on incident falls during follow-up. Univariate analysis was performed to screen for potential risk factors contributing to falls. Logistic regression analysis was employed to identify the independent risk factors for falls in aMCI and AD. Furthermore, disparities in gray matter volume between the fall and non-fall groups were investigated by voxel-based morphometry (VBM) analysis (the false discovery rate (FDR) correction based on clumps was adopted, p < 0.05).

RESULTS: In this preliminary queue with limited sample size, body mass index (BMI), stride length variability, and medication burden were found to be independent predictors of incident falls by univariate and multivariate analyses. The results of VBM suggested significantly reduced gray matter volume in fallers within the left cerebellar Crus I, lobule VI, and fusiform gyrus; right cerebellar lobule VI, fusiform gyrus, and lobule IV-V; and right superior and middle temporal gyrus, compared with non-fallers.

CONCLUSION: The preliminary findings of this study indicate that BMI, stride length variability, and medication burden may be associated with fall risk and reduced gray matter volume in specific brain region may be a potential neuroanatomical basis for increased risk of falls in AD patients, which need to be further validated in larger cohorts.},
}

@article {pmid41798687,
year = {2026},
author = {He, Q and Zhao, Z and Jiang, D and Fei, A},
title = {Diabetes Mellitus Accelerates Alzheimer's Disease Development by Affecting the Gut Microbiome.},
journal = {BioMed research international},
volume = {2026},
number = {},
pages = {9974079},
pmid = {41798687},
issn = {2314-6141},
mesh = {*Gastrointestinal Microbiome/physiology/drug effects ; *Alzheimer Disease/microbiology/pathology/metabolism ; Animals ; Mice ; Brain/metabolism/pathology/diagnostic imaging ; Amyloid beta-Peptides/metabolism ; *Diabetes Mellitus, Experimental/microbiology/complications ; Male ; Butyrates/pharmacology ; Disease Models, Animal ; Positron Emission Tomography Computed Tomography ; Mice, Inbred C57BL ; Fatty Acids, Volatile/metabolism ; },
abstract = {Increasing evidence suggests a link between Alzheimer's disease (AD) and diabetes mellitus (DM). However, the precise mechanisms by which DM contributes to AD remain unclear. This study is aimed at elucidating the potential role of DM in the early stages of AD. Accordingly, a streptozotocin (STZ)-induced diabetic 5 × familial AD (FAD) mouse model was established. Immunohistochemistry and positron emission tomography/computed tomography (PET/CT) scanning were performed to examine amyloid beta (Aβ) deposition in the brain. The integrity of the colonic epithelium was assessed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence staining. Microbial diversity analysis was conducted for 5 × FAD mice with and without STZ-induced DM to determine shifts in intestinal flora profiles. After oral administration of butyrate to STZ-treated 5 × FAD mice, we observed that Aβ deposition in the brain was decreased, and the intestinal flora improved. Immunohistochemistry and PET/CT findings revealed a marked increase in Aβ formation in the brains of 5 × FAD mice treated with STZ. qRT-PCR and immunofluorescence staining revealed severe intestinal barrier dysfunction in these mice. Gut microbiota sequencing indicated significant dysbiosis in STZ-treated 5 × FAD mice, characterized by a reduction in short-chain fatty acid (SCFA)-producing species. After oral administration of butyrate, Aβ deposition in the brains of STZ-treated 5 × FAD mice was significantly reduced, and beneficial changes occurred in the intestinal flora, including increases in bacteria associated with SCFA production and neurological function. Dysregulation of the gut microbiome may exacerbate cerebral amyloidosis during AD pathogenesis. Microbes associated with SCFA production may play a beneficial role in AD treatment, and butyrate supplementation can significantly delay AD progression.},
}

*Gastrointestinal Microbiome/physiology/drug effects
*Alzheimer Disease/microbiology/pathology/metabolism
Animals
Mice
Brain/metabolism/pathology/diagnostic imaging
Amyloid beta-Peptides/metabolism
*Diabetes Mellitus, Experimental/microbiology/complications
Male
Butyrates/pharmacology
Disease Models, Animal
Positron Emission Tomography Computed Tomography
Mice, Inbred C57BL
Fatty Acids, Volatile/metabolism

@article {pmid41798683,
year = {2026},
author = {Tolboom, N and Verger, A and Preusser, M and Geurts, M and Scheltens, P and Albert, NL},
title = {Drawing parallels between amyloid PET in Alzheimer's disease and amino acid PET in primary and secondary brain tumors.},
journal = {Neuro-oncology advances},
volume = {8},
number = {1},
pages = {vdag043},
pmid = {41798683},
issn = {2632-2498},
abstract = {The evolution of amyloid PET in Alzheimer's disease illustrates the potential path of amino acid PET in neuro-oncology. Initially seen as of limited value, amyloid PET ultimately enhanced diagnostic accuracy, guided management, and became central once therapies demonstrated PET-measured efficacy. Amino acid PET for CNS tumors is at a similar turning point. It refines diagnosis, distinguishes progression from treatment effects, and supports treatment planning. As demand grows and tracer access improves, amino acid PET could follow amyloid PET's trajectory: emerging as a key tool in precision medicine and clinical management and as a surrogate endpoint in therapeutic trials.},
}

@article {pmid41798622,
year = {2026},
author = {Zhou, Y and Yang, P and He, H and Liu, H and Ye, P and Xia, J},
title = {DAB2IP: unifying cardiovascular pathogenesis and cardiovascular brain crosstalk.},
journal = {Frontiers in cardiovascular medicine},
volume = {13},
number = {},
pages = {1660204},
pmid = {41798622},
issn = {2297-055X},
abstract = {Cardiovascular diseases and brain disorders collectively represent a major global health burden. Not only do they frequently occur as comorbidities, but their pathological mechanisms are also intricately linked through a complex network of cardiovascular-brain crosstalk. Cardiovascular diseases (CVDs) and neurological disorders together impose high global health burdens. The DAB2IP gene, initially characterized as a tumor suppressor, serves as a multifunctional regulator and performs roles in both the cardiovascular and neurological systems. In atherosclerosis (AS), DAB2IP suppresses the inflammation and apoptosis of endothelial cells (ECs) through the TNF signaling pathways, inhibits phenotypic switching of vascular smooth muscle cells (VSMCs) via the JAK-STAT and PI3K-Akt axes, and attenuates plaque angiogenesis via VEGF-related pathways. It is genetically associated with coronary artery disease (CAD), aortic aneurysm (AA), and aortic dissection (AD) risk, and mediates hemodynamic stress responses and glucose/lipid metabolic dysregulation in the vasculature. In the cardiovascular brain circuit (CBC), DAB2IP governs cortical neuron migration through the Rap1-integrin pathways, modulates the integrity of the blood-brain barrier (BBB) in Alzheimer's disease models via apoptosis-related signaling, and associates with arterial adventitial immune-neural remodeling. Newly developed DAB2IP-targeted strategies, including epigenetic modulators and engineered exosomal circRNA delivery systems, demonstrate preclinical potential but require rigorous validation in various models to assess long-term biosafety and organ-specific efficacy.},
}

@article {pmid41798477,
year = {2026},
author = {Canal de Velasco, LM and González Flores, JE and Vargas, L and Morales Arteaga, JL},
title = {Psychiatric and Cognitive Effects of Testosterone Therapy in Adult Men: A Systematic Review of Clinical Evidence and Mechanistic Insights.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e102894},
pmid = {41798477},
issn = {2168-8184},
abstract = {Testosterone plays a critical role in male physical and psychological health, influencing not only reproductive and metabolic functions but also mood, cognition, and overall mental well-being. Age-related testosterone decline has been associated with depressive symptoms, cognitive impairment, and reduced quality of life. Although testosterone therapy (TT) is well established for somatic outcomes, its psychiatric and cognitive effects remain inconsistently characterized across clinical trials. The objective is to systematically review the evidence on the effects of TT on psychiatric and cognitive outcomes in adult men, compared with placebo or standard care, and to evaluate associated safety findings. This systematic review followed PRISMA guidelines and was registered in PROSPERO (ID: 1163108). Comprehensive searches were conducted in MEDLINE, EMBASE, Cochrane Library, ScienceDirect, and Google Scholar up to October 2025. Eligible studies included randomized controlled trials (RCTs) and observational studies evaluating TT (any route or dose) in adult men with psychiatric or cognitive endpoints. Data extraction was performed independently by two reviewers, using the PICOS framework. Risk of bias was assessed using the Cochrane RoB 2 tool. A total of 11 RCTs, encompassing over 600 male participants (aged 18-85 years), were included. Populations ranged from healthy eugonadal men to older hypogonadal adults, and patients with treatment-resistant depression (TRD) or mild Alzheimer's disease. TT significantly improved depressive symptoms in men with TRD (p < 0.05), and enhanced specific cognitive domains - particularly verbal memory and visuospatial processing (p < 0.05) - in older or hypogonadal men. Global cognition and anxiety outcomes showed inconsistent effects. Quality of life and sexual function consistently improved across studies, while adverse events were mild and transient (mainly acne, edema, or skin irritation). No major cardiovascular, hepatic, or thromboembolic complications were reported. However, evidence certainty remains moderate due to small sample sizes, brief intervention periods, and heterogeneous methodologies. TT should be considered a complementary, not primary, approach in the management of depressive and cognitive symptoms in hypogonadal men, implemented under endocrinological supervision, with regular biochemical and clinical monitoring. Larger, long-term RCTs are warranted to confirm efficacy, optimize dosing, and define long-term neuropsychiatric safety.},
}

@article {pmid41798231,
year = {2026},
author = {Grover, D and Prakash, O and Shingarakhiya, S},
title = {Catatonia in a patient with Alzheimer's dementia.},
journal = {Indian journal of psychiatry},
volume = {68},
number = {2},
pages = {210-211},
pmid = {41798231},
issn = {0019-5545},
}

@article {pmid41798063,
year = {2026},
author = {Xu, X and Cheng, Y and Liu, X and Ding, W and Zhu, Z and Wu, L and Ling, Z and Gao, Y and Yue, J},
title = {Microbial SCFAs as epigenetic mediators: fine-tuning the gut-brain axis in neurodegenerative disorders.},
journal = {Current research in microbial sciences},
volume = {10},
number = {},
pages = {100574},
pmid = {41798063},
issn = {2666-5174},
abstract = {The gut-brain axis is a bidirectional communication system linking the gastrointestinal tract and the central nervous system (CNS). Short-chain fatty acids (SCFAs) are microbial metabolites produced through the anaerobic fermentation of dietary fiber. Growing evidence positions SCFAs as critical signaling molecules within this axis, capable of modulating key neurobiological processes relevant to neurodegenerative diseases (NDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD). SCFAs exert neuroprotective effects by mitigating neuroinflammation, promoting neurogenesis, enhancing synaptic plasticity, and preserving blood-brain barrier integrity. These actions are largely mediated through epigenetic mechanisms. Butyrate functions as a histone deacetylase inhibitor to alter gene expression related to neuronal survival, inflammation, and metabolism. SCFAs also influence DNA methylation dynamics via modulation of DNA methyltransferases and ten-eleven translocation (TET) enzymes. Emerging findings suggest their involvement in novel histone modifications, such as lactylation. This review synthesizes current understanding of SCFA production, metabolic fate, and their multifaceted epigenetic actions in the brain, while evaluating their translational and therapeutic potential. Gut-derived SCFAs represent promising modulators of the brain's epigenetic landscape. Elucidating their mechanisms offers a foundation for developing novel interventions, including dietary, probiotic, and epigenetics-based strategies, for the prevention and treatment of NDs.},
}

@article {pmid41797971,
year = {2026},
author = {Wang, X and Ge, X and Di, X and Zou, Z and Lei, D and Wang, Z and Hou, J and Yang, Y and Zhang, W and Yin, Y and Lei, X and Long, Y and Jian, X and Li, X},
title = {Astragalus Polysaccharides Can Effectively Alleviate Cognitive Impairment in Mice With Alzheimer's Disease by Regulating the Gut Microbiota.},
journal = {Food science & nutrition},
volume = {14},
number = {3},
pages = {e71623},
pmid = {41797971},
issn = {2048-7177},
abstract = {Gut microbiota disruption has been implicated in Alzheimer's disease (AD) pathogenesis. Although Astragalus polysaccharides (APS) exert neuroprotective effects and modulate gut microbial composition, the precise mechanisms underlying these actions remain unknown. This research sought to clarify how APS modulates the gut microbiota during AD progression. Triple-transgenic (3xTg) AD mice received daily oral APS for 4 weeks. Cognitive performance was evaluated with the Morris water maze (MWM). Immunofluorescence (IF), immunohistochemistry (IHC), and western blotting measured β-amyloid (Aβ) deposition and microglial and astrocyte markers. IHC also evaluated intestinal tight-junction proteins (zonula occludens-1 and occludin). Inflammatory markers in the brain, blood, and intestine were quantified using enzyme-linked immunosorbent assay (ELISA). Gut microbiota was analyzed through 16S rRNA sequencing. Treatment with APS significantly improved learning and memory performance in 3xTg mice. APS administration reduced cerebral Aβ deposition, decreased phosphorylated tau, presenilin-1, and β-secretase 1 levels, and elevated ADAM10 expression. APS significantly altered gut microbiota, notably increasing Akkermansia and decreasing Alistipes. At the intestinal level, APS enhanced expression of tight-junction proteins ZO-1 and occludin and reversed AD-associated structural alterations in the intestinal lining. Furthermore, APS reduced inflammatory cytokine levels in intestinal tissue, peripheral blood, and brain tissue, as reflected by modulated IL-4, IL-10, TGF-β, TNF-α, IL-1β, and IL-6 expressions. The attenuation of neuroinflammation may be attributed to the inhibitory effect of APS on microglial and astrocyte activation. APS reduces neuroinflammation in AD by modulating gut microbiota, contributing to cognitive and pathological improvements, thus indicating its therapeutic potential for AD.},
}

@article {pmid41797922,
year = {2026},
author = {Lysaker, CR and Johnson, CN and Csikos, V and Franczak, E and Tetlow, AL and Benson, M and Thyfault, JP and Geiger, PC and Morris, JK and Wilkins, HM},
title = {APOE4 drives widespread changes to the hepatic proteome and alters metabolic function.},
journal = {iScience},
volume = {29},
number = {3},
pages = {115035},
pmid = {41797922},
issn = {2589-0042},
abstract = {Apolipoprotein E (APOE) is essential for lipid homeostasis and has been extensively studied in Alzheimer's disease (AD). Individuals carrying an APOE4 allele have an increased risk of AD and exhibit deficits in energy metabolism, including glucose utilization and mitochondrial dysfunction. While the role of APOE in the liver is well characterized, the impact of APOE genotype on hepatic health and metabolism remains poorly understood. We sought to investigate this using young APOE3 and APOE4-targeted replacement mice and isogenic-induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (iHLCs). Proteomic and functional assays show that APOE4 causes extensive changes to liver mitochondrial function in a sex-specific manner in mice and alters glucose and lipid metabolism. APOE4 also impairs mitochondrial function in iHLCs, shifts metabolism towards glycolysis, increases reliance on fatty acid utilization, and drives lipid accumulation. Together, these findings show that APOE genetic variation causes mitochondrial dysfunction and rewires hepatic metabolism.},
}

@article {pmid41797877,
year = {2026},
author = {Chaurasiya, M and Cholleti, SN and Prasad, G and Vindal, V},
title = {A Meta-analysis to Identify Common Key Genes Across Ageing, Alzheimer's and Parkinson's Diseases.},
journal = {Annals of neurosciences},
volume = {},
number = {},
pages = {09727531261420619},
pmid = {41797877},
issn = {0972-7531},
abstract = {BACKGROUND: Ageing (AG) is associated with cognitive decline and an increased risk of developing neurodegenerative diseases (NDs) like Alzheimer's disease (AD) and Parkinson's disease (PD). While individual diseases have been widely studied, cross-condition convergence at the transcriptomic and regulatory levels has not been systematically defined.

OBJECTIVE: To identify a conserved molecular core shared across AG, AD and PD and to understand its functional and regulatory architecture using integrative network biology.

METHODS: Four independent human brain transcriptomic datasets (n = 173 samples) representing AG, AD and PD were analysed using false discovery rate correction (FDR < 0.05). Genes commonly dysregulated across all conditions were identified via intersection analysis. Functional enrichment, protein-protein interaction (PPI) network analysis, and microRNA (miRNA) regulatory mapping were performed using clusterProfiler, STRING and multiMiR frameworks.

RESULTS: A conserved set of 142 genes was identified across AG, AD and PD, with 94.4% exhibiting consistent directionality of regulation. AG clustered transcriptionally closer to AD than PD, while PD displayed stronger amplitude of dysregulation. Functional enrichment analysis revealed dominant involvement in synaptic signalling, axonal transport, vesicle trafficking and calcium homeostasis. Network analysis identified three essential regulatory hubs, CALM3, CDC42 and RAB3A. They are critical to neuronal signalling and cytoskeletal dynamics. miRNA analysis revealed coordinated regulation of hub genes by disease-associated miRNAs, including miR-29, miR-34, miR-7 and miR-195, and identified shared disease-associated regulators across AG, AD and PD conditions.

CONCLUSION: This study defines a shared neurodegenerative molecular core that bridges physiological AG with pathological neurodegeneration. The integration of transcriptomic, network, and miRNA analyses reveals systems-level convergence and identifies key regulatory nodes as attractive targets for cross-disease therapeutic strategies.},
}

@article {pmid41797865,
year = {2026},
author = {Atiya, S and Aschebrook-Kilfoy, B and Konda, S and , },
title = {Comparative methods for determining MoCA, MMSE, and CDR cut-offs in Alzheimer's disease: insights from the ADNI study.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70291},
pmid = {41797865},
issn = {2352-8729},
abstract = {INTRODUCTION: Accurate cut-off values for the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) are essential for detecting and staging Alzheimer's disease-related cognitive impairment. Prior studies often relied on a single statistical method, potentially misaligning thresholds with clinical priorities.

METHODS: We analyzed cognitive assessments from 883 Alzheimer's Disease Neuroimaging Initiative participants classified as cognitively normal, mild cognitive impairment (MCI), or clinical impairment (CI). Optimal thresholds were identified using Euclidean distance, Index of Union, maximum product of sensitivity and specificity, and Youden's J Index. Sensitivity, specificity, and area under the curve were calculated.

RESULTS: For MCI, MoCA cut-offs were 24 (three methods) and 25 (Youden's J Index). For CI, MoCA cut-offs were 17 (Youden's J Index) and 18 (others). MMSE (28, 24) and CDR (0.5, 1) cut-offs were consistent.

DISCUSSION: MoCA thresholds vary by method, requiring context-specific selection, while MMSE and CDR cut-offs remain stable.},
}

@article {pmid41797864,
year = {2026},
author = {Perrin, A and Letrilliart, L and Gilbert, T and Montellier, M and Grangé, C and Garnier-Crussard, A},
title = {Blood-based biomarkers for Alzheimer's disease in primary care: A French qualitative study exploring perspectives of general practitioners.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {1},
pages = {e70301},
pmid = {41797864},
issn = {2352-8729},
}

@article {pmid41797563,
year = {2026},
author = {Thacker, A and Parks, AL and Dohan, D and Ramirez Gomez, LA and Ritchie, CS and Shah, SJ and Gale, SA and Paladino, J},
title = {A qualitative study investigating clinician experiences with lecanemab implementation across seven academic medical centers.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261422486},
doi = {10.1177/13872877261422486},
pmid = {41797563},
issn = {1875-8908},
abstract = {BackgroundThe recent approval of anti-amyloid therapies (AATs) for Alzheimer's disease (AD) has introduced new complexities into clinical care. While offering therapeutic promise, AATs necessitate changes in practice models, infrastructure, and team responsibilities. Understanding clinician and system-level adaptations is critical to guide implementation.ObjectiveTo explore how clinicians adjust clinical workflows and care processes when integrating anti-amyloid treatments into AD management.MethodsWe conducted semi-structured interviews with neurology and geriatrics clinicians across seven academic medical centers to explore perspectives on AAT implementation. An interdisciplinary team used hybrid deductive-inductive coding and thematic analysis to identify themes.ResultsTwenty-seven clinicians (17 neurology, 10 geriatrics) participated. Three themes emerged: (1) Structural adaptations: Sites developed governance committees, eligibility protocols, and workflows for referrals, administration, and monitoring. Some hired new staff, and protocols evolved with experience. (2) Diagnostic shifts: Clinicians reported heightened pressure for earlier, more precise diagnoses, prompting greater biomarker use and structured disclosure visits incorporating treatment discussions. (3) Cultural change: While clinicians described optimism about disease-modifying therapies, they expressed ethical concerns about resource allocation, over-medicalization of early dementia, and diversion of resources from broader dementia care.ConclusionsThe findings reflect evolving institutional protocols, clinical roles and responsibilities, and ethical tensions within the clinical workforce in response to AAT administration and access to early diagnosis and treatment.},
}

@article {pmid41797557,
year = {2026},
author = {Proulx, D and Kirk, A and O'Connell, M and Morgan, D},
title = {Does anticholinergic medication use on presentation to a rural memory clinic predict cognitive or functional decline over one year?.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261424232},
doi = {10.1177/13872877261424232},
pmid = {41797557},
issn = {1875-8908},
abstract = {BackgroundAnticholinergic medications carry increased risk of worsening cognition, particularly in patients with dementia.ObjectiveCognitive and functional scores of patients were compared at 1-year follow up after cessation of prior anticholinergic medications to those who were not taking anticholinergics at baseline to assess whether prior anticholinergic use affected dementia prognosis in memory clinic patients.MethodsLongitudinal data from 578 consecutive patients with diagnoses including Alzheimer's disease (AD), frontotemporal and vascular dementia, Lewy body dementia, mild cognitive impairment and dementia due to non-AD etiologies compared patients taking anticholinergic drugs to those taking none at intake. Anticholinergic drugs were discontinued in all patients at initial visit. Mini-Mental Status Examination (MMSE) and Functional Activities Questionnaire (FAQ) were administered at intake and 1-year follow up.ResultsBetween the no-anticholinergic and anticholinergic groups, MMSE at baseline did not significantly differ when the entire sample was compared. In addition, MMSE score change between baseline and follow-up did not significantly differ. Similarly, no significant differences were observed between groups in FAQ at baseline or in FAQ change between timepoints. Subgroup analysis of only those with AD yielded statistically significant differences in initial MMSE. However, these groups had statistically similar follow-up MMSE. Although initial FAQ scores were similar, there were significant differences in follow-up FAQ in patients with AD.ConclusionsFindings suggest that patients with AD presenting on anticholinergic medications may do worse cognitively and functionally than those who were never on anticholinergics despite baseline discontinuation. Anticholinergic medication use in older adults should be approached cautiously.},
}

@article {pmid41797478,
year = {2026},
author = {Wu, F and Huang, J and Wang, J and Wu, R and Zhang, H and Jin, C and Chen, C and Zhou, R and Cen, P and Tian, L and Zheng, Y and Cai, X and Tian, M and Zhang, H and Zhong, Y},
title = {Prussian Blue Nanozyme Disrupts the Self-Reinforcing Loop of Tauopathy via Triple-Action Mechanism.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e05286},
doi = {10.1002/adhm.202505286},
pmid = {41797478},
issn = {2192-2659},
support = {2021YFA1101700//National Key Research and Development Program of China/ ; 2021YFE0108300//National Key Research and Development Program of China/ ; 82030049//National Natural Science Foundation of China/ ; 32027802//National Natural Science Foundation of China/ ; 82394433//National Natural Science Foundation of China/ ; 82361148130//National Natural Science Foundation of China/ ; 82030050//National Natural Science Foundation of China/ ; T2394534//National Natural Science Foundation of China/ ; 82302262//National Natural Science Foundation of China/ ; 82302261//National Natural Science Foundation of China/ ; 226-2024-00059//Fundamental Research Funds for the Central Universities/ ; LMS25H180002//Zhejiang Provincial Natural Science Foundation of China/ ; //Innovative research team of high-level local universities/ ; },
abstract = {Tauopathies, such as Alzheimer's disease, are driven by a self-reinforcing pathological triad of tau aggregation, oxidative stress, and autophagy dysfunction, which remains inadequately addressed by single-target therapies. Herein, we engineer an ultrasmall Prussian blue nanozyme (PBzyme) as a multienzyme-mimetic and multi-target agent to concurrently disrupt this vicious cycle. PBzyme functions as a potent tau fibril inhibitor, with molecular dynamics simulations revealing high-affinity binding to β-sheet domains (-400 kJ/mol), thereby reducing tau phosphorylation and hippocampal burden. In parallel, PBzyme acts as a multifunctional antioxidant enzyme mimic, efficiently neutralizing •OH, O2 [-], and H2O2 to alleviate oxidative injury. Furthermore, PBzyme restores autophagic flux by activating AMPK/ULK1 signaling while inhibiting the mechanistic target of rapamycin (mTOR), thereby promoting the clearance of tau aggregates. In an okadaic acid-induced tauopathy rat model, PBzyme treatment effectively preserved synaptic integrity, suppressed neuroinflammation, mitigated neuronal loss, and rescued cognitive deficits. Notably, PBzyme enters cells to counteract intracellular tau and ROS, overcoming a key limitation of conventional biologics. This work establishes PBzyme as an integrated nanoagent offering a synergistic therapeutic strategy against tauopathies and other ROS-related neurodegenerative diseases.},
}

@article {pmid41797443,
year = {2026},
author = {Hall, S and Garcia, L and Stahmer, M and Griffin, P and Carrillo, MC and Edelmayer, RM},
title = {The Alzheimer's Association TrialMatch-Increasing awareness of all dementia trials.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71250},
doi = {10.1002/alz.71250},
pmid = {41797443},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease ; *Clinical Trials as Topic ; *Patient Selection ; *Awareness ; United States ; *Dementia ; },
abstract = {BACKGROUND: Roughly 7.2 million older Americans are living with Alzheimer's disease (AD). Research participation remains one of the largest barriers facing dementia research advancements.

METHODS: TrialMatch is a dementia research awareness tool. TrialMatch consolidates research opportunities to serve as an open-access, centralized, and user-friendly resource to identify research opportunities. Between August 2020 and June 2024, we tracked the number of research opportunities available, enrollment targets, and TrialMatch engagement.

RESULTS: TrialMatch maintained a database of over 700 opportunities and received 18,802 calls and 122,461 web sessions, and provided 17,725 referrals to opportunities. An estimated 1,867,403 participants are needed to populate all the ongoing studies in the United States.

DISCUSSION: By using a broad inclusion criteria, TrialMatch highlights the burden that AD/ADRD research faces with recruitment. While TrialMatch has demonstrated its ability to serve as an awareness tool, future analyses are needed to better evaluate the impact of the tool on enrollment.},
}

Humans
*Alzheimer Disease
*Clinical Trials as Topic
*Patient Selection
*Awareness
United States
*Dementia

@article {pmid41797441,
year = {2026},
author = {Wearn, A and Onuska, KM and Schmitz, TW and Turner, GR and Spreng, RN},
title = {The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71249},
doi = {10.1002/alz.71249},
pmid = {41797441},
issn = {1552-5279},
support = {AG068563// National Institute on Aging/ ; AARG-22-927100/ALZ/Alzheimer's Association/United States ; 317644//Fonds de Recherche du Québec - Santé/ ; //McGill University: Jeanne Timmins Costello Postdoctoral Fellowship/ ; },
mesh = {*Alzheimer Disease/pathology/metabolism/physiopathology/etiology ; Humans ; tau Proteins/metabolism ; Amyloid beta-Peptides/metabolism ; *Brain/pathology/metabolism ; *Neurons/pathology/metabolism ; Animals ; Plaque, Amyloid/pathology/metabolism ; Risk Factors ; },
abstract = {Sporadic Alzheimer's disease (AD) is associated with numerous risk factors, yet its precise cause remains unclear. Here, we describe a novel framework for AD pathogenesis, whereby diverse risk factors converge on neuromodulatory subcortical systems to confer AD risk or resilience. Neuromodulatory projection neurons are uniquely fragile due to their large size, sparse myelination, and high basal metabolic demands. We propose that the increased prevalence of AD in older adult populations likely reflects a universal weakness within these projection systems, which is increasingly exposed as cellular transport and maintenance mechanisms deteriorate with age. The key insight of this "neuromodulatory fragility hypothesis" is that neuromodulatory system dysfunction is sufficient to explain both tau hyperphosphorylation and amyloid beta plaque formation, the two pathological hallmarks of AD. We therefore predict that strengthening or preserving the endogenous functions of these systems in midlife represents the most effective strategy for preventing AD.},
}

*Alzheimer Disease/pathology/metabolism/physiopathology/etiology
Humans
tau Proteins/metabolism
Amyloid beta-Peptides/metabolism
*Brain/pathology/metabolism
*Neurons/pathology/metabolism
Animals
Plaque, Amyloid/pathology/metabolism
Risk Factors

@article {pmid41797133,
year = {2026},
author = {Sonu, and Alomar, TS and Parveen, BR and Altalhi, R and Sayed, AA and AlMasoud, N and Abdel-Daim, MM and Yadav, P and Kumar, A and Kapoor, K},
title = {Synthesis, spectral characterization, and cholinesterase inhibitory evaluation of benzothiazole-linked oxadiazole derivatives as potential anti-Alzheimer's agents.},
journal = {Bioorganic chemistry},
volume = {174},
number = {},
pages = {109687},
doi = {10.1016/j.bioorg.2026.109687},
pmid = {41797133},
issn = {1090-2120},
abstract = {A series of eleven novel benzothiazole-based oxadiazole derivatives (K1-K11) were synthesized using 2-amino-4-methoxybenzenethiol as the key precursor. The structures of the synthesized compounds were confirmed by IR, [1]H NMR, [13]C NMR, and mass spectrometry. All derivatives were evaluated for their cholinesterase inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with donepezil used as the reference drug. Compounds K2 and K9 exhibited potent AChE inhibition, while K11 and K7 showed notable BChE inhibitory activity, with IC50 values comparable to the standard. Molecular docking studies supported the experimental results, revealing strong binding interactions of K2 and K7 with AChE and BChE, respectively. In silico ADME analysis indicated favorable drug-like properties for all compounds, suggesting their potential as promising leads for Alzheimer's disease therapy.},
}

@article {pmid41797094,
year = {2026},
author = {Solfrizzi, V and Imbimbo, BP},
title = {Long-term treatment of early Alzheimer's disease with donanemab.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {4},
pages = {100512},
doi = {10.1016/j.tjpad.2026.100512},
pmid = {41797094},
issn = {2426-0266},
}

@article {pmid41796868,
year = {2026},
author = {Ji, R and Zang, Z and Sun, Y and Fu, X and Lan, S and Li, X and Guo, L and Liu, X and Peng, C and Wang, M and Kuang, H and Wang, Z},
title = {Exploring the effect of Kaixin San on Alzheimer's disease by regulating the Keap1/Nrf2/GPX4 signaling pathway to inhibit ferroptosis based on metabolomics and gut microbiota analysis.},
journal = {Fitoterapia},
volume = {},
number = {},
pages = {107162},
doi = {10.1016/j.fitote.2026.107162},
pmid = {41796868},
issn = {1873-6971},
abstract = {Alzheimer's disease (AD), as a common neurodegenerative disease, seriously affects the cognitive function and quality of life of patients, bringing a heavy burden to society and families. In recent years, traditional Chinese medicine (TCM) formula Kaixin San (KXS) has shown considerable potential in the treatment of AD. KXS can ameliorate cognitive dysfunction in AD model animals, but its action mechanism remains not fully elucidated. This study aims to further elucidate the action mechanism of KXS. To this end, we employed a variety of advanced technical methods, including neuropathological, molecular biological, metabolomic, and gut microbiota analysis techniques, to conduct systematic multi-dimensional research. The results demonstrated that KXS can significantly improve the learning and memory abilities of AD rats, alleviate hippocampal neuronal damage, reduce β-amyloid (Aβ) expression, and activate antioxidant activity by targeting the Keap1/Nrf2/GPX4 signaling pathway, thereby inhibiting ferroptosis. Metabolomic analysis reveals that KXS exerts a regulatory effect on metabolites, while gut microbiota analysis shows that KXS significantly promotes the proliferation of beneficial bacteria and reduces the abundance of pathogenic bacteria, thereby regulating gut microbiota homeostasis, inhibiting excessive activation of neuroinflammation, and alleviating neuronal damage induced by inflammatory factors. Further correlation analysis reveals a strong correlation between metabolites and gut microbiota in AD rats. In addition, KXS inhibits ferroptosis and oxidative stress by activating the Keap1/Nrf2/GPX4 signaling pathway, and simultaneously regulates serum lipid metabolism-related pathways to maintain metabolic homeostasis and gut microbiota balance, thereby inhibiting excessive neuroinflammatory activation and alleviating neuronal damage.},
}

@article {pmid41796789,
year = {2026},
author = {Wang, S and Wei, Y and Li, Y and Qing, H and Yan, Y and Cheng, Y},
title = {Effects of different exercise modalities on four major neurodegenerative diseases and their molecular mechanisms.},
journal = {Neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuroscience.2026.03.001},
pmid = {41796789},
issn = {1873-7544},
abstract = {Neurodegenerative diseases are marked by progressive neuronal damage and currently lack a cure. Recently, exercise has emerged as a promising non-pharmacological approach to potentially slow disease progression and enhance cognitive function. This narrative review summarizes the effects of various exercise modalities-including aerobic exercise, resistance training, and balance training-on four major neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, and spinocerebellar ataxia), as well as their underlying molecular mechanisms. Evidence from existing studies suggests that aerobic exercise activates the AMPK/PGC-1α signaling pathway, promoting mitochondrial biogenesis and supporting astrocyte function, which in turn reduces β-amyloid accumulation and neuroinflammation. Resistance and balance training primarily improve muscle strength and coordination, leading to better motor performance and quality of life. Additionally, exercise modulates the release of neurotrophic factors, enhancing synaptic plasticity and neurogenesis. The review also discusses optimal exercise protocols tailored to specific diseases, providing a foundation for clinical application and future research. Moving forward, studies should focus on personalized exercise regimens and long-term outcomes to maximize the benefits of non-pharmacological interventions in neurodegenerative diseases.},
}

@article {pmid41796723,
year = {2026},
author = {Soni, U and Pujari, R},
title = {Elucidating the molecular targets in Alzheimer's disease: Advances and therapeutic implications.},
journal = {Progress in neuro-psychopharmacology & biological psychiatry},
volume = {},
number = {},
pages = {111660},
doi = {10.1016/j.pnpbp.2026.111660},
pmid = {41796723},
issn = {1878-4216},
abstract = {Alzheimer's disease (AD), the most prevalent form of dementia, is intrinsically linked to the biological processes of ageing, which serve as its greatest risk factor. As global life expectancy rises, age-associated neurodegenerative disorders like AD impose an escalating burden on public health systems and economies. Ageing is accompanied by a complex interplay of cellular and molecular alterations, including oxidative stress, mitochondrial dysfunction, impaired proteostasis, chronic neuroinflammation, and epigenetic drift, all of which converge to disrupt neuronal integrity and function. In AD, these ageing-related mechanisms accelerate pathological hallmarks such as amyloid-β plaque deposition, tau hyperphosphorylation, synaptic loss, and neurodegeneration. Recent advances in molecular neuroscience have unveiled a spectrum of novel targets involved in the pathogenesis of AD, ranging from secretases and tau kinases to microglial receptors and mitochondrial bioenergetic regulators. This review elucidates the therapeutic strategies aimed at modulating these targets, including the use of small-molecule inhibitors, monoclonal antibodies, gene therapies, and epigenetic modifiers. Additionally, the impact of blood-brain barrier integrity on neuronal energy metabolism and its correlation with AD pathology is examined. The findings underscore the importance of interdisciplinary approaches in AD research, highlighting future directions and challenges in developing effective treatments. By advancing our understanding of the molecular nexus of AD, this work aims to contribute to the ongoing efforts to mitigate the effects of this debilitating condition and improve patient outcomes.},
}

@article {pmid41796707,
year = {2026},
author = {Gong, P and Li, X and Lin, D and Ding, X and Liu, Z and Chen, F},
title = {2.5D HAU-Net with Gated Spatial Attention for Automatic Hippocampus Segmentation in MRI.},
journal = {Journal of neuroscience methods},
volume = {},
number = {},
pages = {110730},
doi = {10.1016/j.jneumeth.2026.110730},
pmid = {41796707},
issn = {1872-678X},
abstract = {BACKGROUND: The hippocampus is a key brain region and biomarker for Alzheimer's disease (AD). Accurate automated hippocampal segmentation is essential for anatomical and pathological analysis. However, the gap between model complexity and available computational resources hampers the clinical deployment of computer-aided diagnosis (CAD) systems, often resulting in limited accuracy and generalization.

NEW METHOD: This study introduces a 2.5D U-Net-based framework that integrates an attention mechanism for efficient and accurate MRI hippocampal segmentation. Three consecutive slices (anterior, middle, posterior) are stacked to form 2.5D input representations, enhancing spatial context. The proposed HAU-Net incorporates a gated spatial attention module to improve feature selectivity and robustness. A hybrid Dice-BCE loss is used to address class imbalance and accelerate convergence.

RESULTS: Experiments on the MSD Task04 Hippocampus and HarP datasets demonstrate strong performance, achieving Dice scores of 91.05% and 90.62%, respectively, with stable results across datasets.

Compared with the baseline U-Net and other widely used segmentation models, the proposed 2.5D attention-enhanced network achieves higher Dice similarity coefficients and better generalization while maintaining computational efficiency suitable for practical use.

CONCLUSIONS: The attention-guided 2.5D HAU-Net provides an effective, robust, and resource-efficient solution for automated hippocampal segmentation. Its strong performance and low computational demand support its potential for real-world clinical application and broader use in neuroscience and medical imaging.},
}

@article {pmid41796494,
year = {2026},
author = {Cheng, R and Guo, Z and Xiao, Z and Yu, B and Tang, X and Xu, P and Qiu, P},
title = {Activity-tunable bimetallic iron-cobalt nanoflowers integrated with smartphones for rapid detection of human uric acid.},
journal = {Analytica chimica acta},
volume = {1397},
number = {},
pages = {345269},
doi = {10.1016/j.aca.2026.345269},
pmid = {41796494},
issn = {1873-4324},
mesh = {*Uric Acid/analysis/blood ; Humans ; *Iron/chemistry ; *Smartphone ; *Cobalt/chemistry ; *Nanostructures/chemistry ; Colorimetry ; Limit of Detection ; *Biosensing Techniques ; },
abstract = {BACKGROUND: Uric acid (UA), a key biomarker linked to diseases like gout and Alzheimer's, can be detected using nanozyme technology. Developing sensitive nanozyme-based biosensors for UA is therefore crucial for early disease diagnosis and prevention.

RESULTS: In this work, activity-tunable nanoflowers (FeCo NFs) were successfully synthesized with different metal ratios demonstrated varying the peroxidase-like and oxidase activities. A dual-mode assay (ratiometric fluorescence and colorimetric) based on functionalized with amino groups (FeCo NFs-NH2) was proposed with LOD as low as 0.41 μM and 0.31 μM, respectively. Electron spin resonance measurements revealed that the difference in the catalytic activity of nanozymes with different metal ratios stems from their varying •OH generation capabilities. Furthermore, the fluorescence of FeCo NFs-NH2 could be quenched by 2,3-diaminophenazine (DAP) via inner filter effect and photoinduced electron transfer, which was investigated in detail with the aid of the Stern-Volmer and Parker equations. Finally, a smartphone-based detection platform was developed, enabling portable, instrument-free, and sensitive detection of UA.

SIGNIFICANCE: This work fully unites and utilizes the advantages of multifunctional probe and dual-channel detection for reliable serodiagnosis and related diseases evaluation. Moreover, this in-depth study has made guiding progress in the regulation of catalytic activity of metal nanoenzymes, especially in the regulation of oxidase activity and peroxidase activity.},
}

*Uric Acid/analysis/blood
Humans
*Iron/chemistry
*Smartphone
*Cobalt/chemistry
*Nanostructures/chemistry
Colorimetry
Limit of Detection
*Biosensing Techniques

@article {pmid41796440,
year = {2026},
author = {Thakor, PM and Patel, JD and Patel, RJ and Chaki, SH and Khimani, AJ and Vaidya, YH and Raol, GG and Thakor, P and Thakkar, AB},
title = {Multifaceted Exploration of a New Schiff Base and Its Complexes: Thermal Properties and Biomedical Potential.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {3},
pages = {e70766},
doi = {10.1002/jbt.70766},
pmid = {41796440},
issn = {1099-0461},
mesh = {Schiff Bases/chemistry/pharmacology/chemical synthesis ; Humans ; Animals ; Caenorhabditis elegans/drug effects ; Molecular Docking Simulation ; A549 Cells ; *Antineoplastic Agents/pharmacology/chemistry/chemical synthesis ; *Coordination Complexes/pharmacology/chemistry/chemical synthesis ; alpha-Amylases/antagonists & inhibitors/chemistry/metabolism ; },
abstract = {This study presents the thermal and biomedical evaluation of a newly synthesized imine ligand and its six metal complexes. The synthesis and spectral data are detailed in Part 1 of this work. Here, advanced analyses such as LC-MS, SEM, and XRD were used for physicochemical characterization. Thermal stability was assessed using TGA, DTA, and DTG under inert conditions, with kinetic parameters calculated via the Kissinger-Akahira-Sunose method. Biological evaluations included molecular docking, which showed notable α-amylase inhibition, and MTT assays, which confirmed strong anticancer activity against A549 lung cancer cells. Additionally, the ligand and its complexes demonstrated anti-Alzheimer's and stress-resistance effects in Caenorhabditis elegans.},
}

Schiff Bases/chemistry/pharmacology/chemical synthesis
Humans
Animals
Caenorhabditis elegans/drug effects
Molecular Docking Simulation
A549 Cells
*Antineoplastic Agents/pharmacology/chemistry/chemical synthesis
*Coordination Complexes/pharmacology/chemistry/chemical synthesis
alpha-Amylases/antagonists & inhibitors/chemistry/metabolism

@article {pmid41796339,
year = {2026},
author = {Freihat, O},
title = {Reframing disease burden: validation of DALY-per-case as a per-diagnosis severity metric.},
journal = {Population health metrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12963-026-00469-2},
pmid = {41796339},
issn = {1478-7954},
abstract = {BACKGROUND: Population-weighted metrics (incidence, mortality, disability-adjusted life years (DALYs), mortality to incidence ratio (MIR) can obscure per-case severity for less prevalent but high-impact conditions. This paper introduces DALY per case, total DALYs divided by incident cases, as a standardized estimate of healthy life-years lost per new diagnosis, integrating years of life lost (YLL) and years lived with disability (YLD). Validated using cancers and applied across diverse diseases, the metric enables prevalence-independent severity comparisons.

METHODS: Using GBD 2021, we computed DALY per case across diseases (all ages, both sexes), validated on 34 cancers, and tested generalizability in five non-cancer conditions (type 2-diabetes, tuberculosis, HIV/AIDS, ischemic heart disease, Alzheimer's). We compared rankings with incidence, mortality, and total DALYs. A 2-Dimensional framework plotted total DALYs (population burden) vs. DALY-per-case (individual severity) with median-based quadrant thresholds. Uncertainty intervals (UIs) were propagated per GBD conventions; stability was assessed via relative UI width, band-crossing, and sensitivity analyses. Construct/convergent validity used correlations with 5-year survival Surveillance, Epidemiology, and End Results Program (SEER) and MIR; full and reduced regressions tested independence.

RESULTS: High-severity cancers included malignant bone tumours (27.6 DALYs/case), neuroblastoma (26.3), and brain/CNS (24.9), contrasting with population-dominant burdens such as lung (46.5 million DALYs; 20.4/case) and colorectal (24.4 million; 11.1/case). Relative uncertainty spanned 27% (breast) to 96% (Hodgkin lymphoma); rankings were largely preserved despite wide UIs in select sites. DALY-per-case correlated inversely with 5-year survival (r=-0.72, p < 0.001) and positively with MIR (r = 0.75, p < 0.001). In regression, MIR showed the strongest effect (β = 0.52, p = 0.06); survival lost significance when MIR was included, indicating shared but non-redundant variance.

CONCLUSIONS: DALY-per-case provides a disease-agnostic toolkit, including a 2Dimensional burden-severity framework and validation against existing indicators, to quantify per-diagnosis severity and inform policy across communicable and non-communicable diseases.},
}

@article {pmid41796322,
year = {2026},
author = {Cai, Y and Li, L and Li, Z},
title = {Impact of Klotho genotype on lactylation in Alzheimer's disease and mechanistic insights.},
journal = {Immunity & ageing : I & A},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12979-026-00563-x},
pmid = {41796322},
issn = {1742-4933},
support = {CSXL-22210//Sichuan Applied Psychology Research Center/ ; 2020YJ0175//Sichuan Provincial Department of Science and Technology/ ; },
}

@article {pmid41795936,
year = {2026},
author = {Zou, L and Ye, W and Li, C and Yang, S},
title = {Association between stress hyperglycemia ratio and cognitive function in older patients with diabetes or prediabetes: a cross-sectional study from the NHANES.},
journal = {Endocrine journal},
volume = {},
number = {},
pages = {},
doi = {10.1507/endocrj.EJ25-0437},
pmid = {41795936},
issn = {1348-4540},
abstract = {To explore the association between stress hyperglycemia ratio (SHR) levels and cognitive function in older patients with diabetes or prediabetes. Cognitive function was assessed through a composite Z-score, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) subtest, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). SHR was calculated as the fasting blood glucose divided by the estimated average glucose from glycated hemoglobin. In subsequent analyses, SHR was divided into quartiles (quartiles 1 to 4), with the second quartile serving as the reference group. A weighted linear regression model was used to assess the association between SHR and cognitive function. After adjusting the corresponding covariates, the analysis revealed that compared to the second quartile, the first [β: -0.26; 95% confidence interval (CI): -0.39- -0.12], third (β: -0.13, 95% CI: -0.25- -0.02), and fourth (β: -0.21, 95% CI: -0.36- -0.06) quartiles were all associated with a decrease in Z-score. The first quartile was associated with a decline in AFT (β: -1.46, 95% CI: -2.57- -0.36). The first (β: -3.72, 95% CI: -6.06- -1.38) and fourth (β: -2.58, 95% CI: -4.98- -0.17) quartiles were associated with a decline in DSST. No statistically significant associations were observed between any of the quartile groups and CERAD (all p > 0.05). Both higher and lower SHR were associated with poorer overall cognitive function, with higher and lower SHR being related to worse memory dimensions, while lower SHR was associated with impaired executive function.},
}

@article {pmid41795917,
year = {2026},
author = {Sirag, N and Elfadil, H and Ghabban, AJ and Alasiri, AM and Alnasser, IR and Bedaiwi, HS and Alharbi, SF and Almarwani, MJ and Aljohani, OM and Hassan, HM and Al-Gayyar, MMH and Salama, A},
title = {Ligustilide Attenuates Neuroinflammation and Fibrosis in an Aluminum Chloride-induced Rat Model of Alzheimer's Disease via mTOR/STAT3 Signaling Inhibition.},
journal = {The Keio journal of medicine},
volume = {},
number = {},
pages = {},
doi = {10.2302/kjm.2025-0017-OA},
pmid = {41795917},
issn = {1880-1293},
abstract = {Alzheimer's disease (AD) affects approximately 50 million individuals worldwide and is projected to triple by 2050. Ligustilide is a naturally occurring compound with varied pharmacological actions. Ligustilide has been reported to ameliorate AD by inhibiting PKA/AKAP1 or inducing α-secretase, but no prior research has examined its ability to activate the inflammasome in AD. We aimed to investigate the potential therapeutic effects of ligustilide in rats with AD by assessing the inflammatory and fibrotic pathways. AD was induced in rats by aluminum chloride. Subsequently, some rats were orally administered 20 mg/kg of ligustilide. For structural assessment, hippocampal brain tissue sections were stained with hematoxylin/eosin and subjected to anti-mTOR and anti-phospho-tau antibody staining. The collected samples were then analyzed for gene expression and protein levels of mTOR, STAT3, TGF-β, β-catenin, NFκB, TNF-α, TLR4, and NLRP3. We found that rats treated with ligustilide displayed marked improvements in their behavior. Furthermore, microscopic analysis of hematoxylin/eosin-stained images revealed that ligustilide reduced inflamed tissues and partially dilated blood vessels, without gliosis or vacuolated neuropil. Additionally, ligustilide decreased the expression of mTOR, STAT3, TGF-β, β-catenin, NFκB, TNF-α, TLR4, and NLRP3. In conclusion, ligustilide improved AD in rats and reduced inflammation and fibrosis. This effect is attributed to ligustilide's ability to reduce mTOR and STAT3 activity, thereby suppressing NFκB, TNF-α, TLR4, and NLRP3, and inhibiting the inflammasome pathway. Consequently, this cascade results in decreased STAT3 and TGF-β levels, thereby reducing fibrosis.},
}

@article {pmid41795685,
year = {2026},
author = {Liu-Ambrose, T and Falck, RS and Dao, E and Crockett, RA and Barha, CK and Silva, NCBS and Alkeridy, WA and Best, JR and Hsiung, GR and Field, TS and Madden, KM and Davis, JC and Ten Brinke, LF and Tam, RC},
title = {Resistance training and subcortical vascular cognitive impairment: A 12-month randomized trial.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71245},
doi = {10.1002/alz.71245},
pmid = {41795685},
issn = {1552-5279},
support = {//Jack Brown and Family Alzheimer Research Foundation/ ; G-15-0009019//Heart and Stroke Foundation of Canada/ ; },
mesh = {Humans ; Female ; Male ; *Cognitive Dysfunction/therapy/rehabilitation ; Aged ; *Resistance Training/methods ; *Cerebral Small Vessel Diseases/complications ; Neuropsychological Tests ; Treatment Outcome ; Middle Aged ; },
abstract = {INTRODUCTION: It is unknown whether progressive resistance training (PRT) improves cognitive function in adults with cerebral small vessel disease and mild cognitive impairment (i.e., subcortical vascular cognitive impairment [SVCI]).

METHODS: We conducted a 12-month randomized trial comparing PRT versus balance and tone exercises (BAT) on the Alzheimer's Disease Assessment Scale Cognitive Plus (ADAS-Cog-Plus).

RESULTS: Ninety-one participants were randomized (PRT = 45; BAT = 46); 76 completed the trial. Adherence was not different between groups (p = 0.18). At 12 months, PRT significantly improved ADAS-Cog-Plus scores (estimated mean difference: -0.18; 95% confidence interval [CI: -0.35, -0.01]; p = 0.04). Planned contrasts stratified by sex showed a significant PRT effect on ADAS-Cog-Plus scores for females (mean difference: -0.27; 95% CI: [-0.49, -0.05]; p = 0.02), but not for males. PRT also significantly reduced C-reactive protein (estimated mean difference: -2.93; 95% CI: [-5.36, -0.49]; p = 0.02). No significant differences were observed for other secondary outcomes.

DISCUSSION: PRT may have a small beneficial effect on cognitive function in SVCI.

CLINICAL TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT02669394).},
}

Humans
Female
Male
*Cognitive Dysfunction/therapy/rehabilitation
Aged
*Resistance Training/methods
*Cerebral Small Vessel Diseases/complications
Neuropsychological Tests
Treatment Outcome
Middle Aged

@article {pmid41795676,
year = {2026},
author = {Li, J and Xue, H and Leng, Y and Samus, QM and Nowrangi, M and Szanton, SL and Xue, QL and Li, J},
title = {Television and computer use and dementia risk in older adults with limited leisure or social activities: A prospective cohort study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71259},
doi = {10.1002/alz.71259},
pmid = {41795676},
issn = {1552-5279},
support = {//Johns Hopkins University Catalyst Award/ ; },
mesh = {Humans ; *Television/statistics & numerical data ; Male ; Female ; Aged ; *Dementia/epidemiology ; Prospective Studies ; *Leisure Activities ; Risk Factors ; *Computers/statistics & numerical data ; United Kingdom/epidemiology ; Middle Aged ; Sedentary Behavior ; Cohort Studies ; Apolipoproteins E/genetics ; },
abstract = {INTRODUCTION: Associations between television/computer use and dementia in socially inactive older adults remain unclear, and optimal limits are unknown.

METHODS: We followed 89,671 dementia-free, socially inactive adults aged ≥55 from UK Biobank for a mean of 12.2 years. Adjusted Cox models assessed associations with incident all-cause dementia and subtypes.

RESULTS: Computer use ≤2.4 h/day was associated with lower all-cause dementia risk (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82-0.94), whereas higher use increased risk (HR 1.19, 95% CI 1.05-1.34); patterns were similar for Alzheimer's and vascular dementia. Television viewing showed no association below 2.06 h/day but higher risk thereafter (HR 1.17; 95% CI 1.03-1.32), with a roughly linear increase for vascular dementia. Heavy computer use in apolipoprotein E (APOE) -ε4 homozygotes and higher television viewing in adults < 65 were more harmful.

DISCUSSION: In socially inactive older adults, moderate computer use may be protective, whereas higher computer use and television viewing are linked to increased dementia risk.},
}

Humans
*Television/statistics & numerical data
Male
Female
Aged
*Dementia/epidemiology
Prospective Studies
*Leisure Activities
Risk Factors
*Computers/statistics & numerical data
United Kingdom/epidemiology
Middle Aged
Sedentary Behavior
Cohort Studies
Apolipoproteins E/genetics

@article {pmid41795672,
year = {2026},
author = {Cicero, EC and Flatt, JD and Kaabi, O and Tangpricha, V and Getahun, D and McCracken, C and Lash, TL and Silverberg, MJ and Vupputuri, S and Perkins, M and Barnes, LL and Goodman, M},
title = {Alzheimer's disease and related dementias among transfeminine adults: A cohort study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71277},
doi = {10.1002/alz.71277},
pmid = {41795672},
issn = {1552-5279},
support = {23AARGD-NTF-1028973/ALZ/Alzheimer's Association/United States ; R01AA030275/AA/NIAAA NIH HHS/United States ; K23AG084851/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Alzheimer Disease/epidemiology ; Female ; Male ; Aged ; *Transgender Persons/statistics & numerical data ; Cohort Studies ; *Dementia/epidemiology ; Aged, 80 and over ; Prevalence ; Electronic Health Records ; },
abstract = {INTRODUCTION: We investigated whether Alzheimer's disease and related dementias (ADRD) are more common among transfeminine (TF) adults than among demographically similar cisgender people enrolled in the same health system.

METHODS: We analyzed electronic health records of 856 TF adults aged 65+ and matched cisgender men (CM) and cisgender women (CW) and compared ADRD prevalence across groups by calculating enrollment-adjusted odds ratios (aOR) and 95% confidence intervals (CI).

RESULTS: The aOR of ADRD among TF adults were 1.39 (95% CI: 0.99-1.97) relative to CM and 1.29 (95% CI: 0.92-1.82) relative to CW referents. For TF adults with evidence of receiving gender-affirming hormone therapy (GAHT) receipt, the associations were slightly stronger: 1.75 (1.13-2.69) and 1.70 (1.11-2.60). Results restricted to minoritized ethnoracial groups appeared smaller, but imprecise.

DISCUSSION: These findings suggest that ADRD diagnosis and management may represent a priority in the healthcare of older TF people, particularly those with a history of GAHT.},
}

Humans
*Alzheimer Disease/epidemiology
Female
Male
Aged
*Transgender Persons/statistics & numerical data
Cohort Studies
*Dementia/epidemiology
Aged, 80 and over
Prevalence
Electronic Health Records

@article {pmid41795671,
year = {2026},
author = {Lim, S and Lee, J and Min, PH and Moloney, CM and Mester, CT and Ghatamaneni, S and Senjem, ML and Botha, H and Knopman, DS and McCarter, SJ and Ramanan, VK and Savica, R and Fields, JA and Machulda, MM and Dickson, DW and Reichard, RR and Nguyen, AT and Graff-Radford, J and Schwarz, CG and Gunter, JL and Kantarci, K and Boeve, B and Vemuri, P and Jones, DT and Jack, CR and Petersen, RC and Murray, ME and Lowe, VJ},
title = {Tau PET overlap index correlation with neuropathological findings.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71241},
doi = {10.1002/alz.71241},
pmid = {41795671},
issn = {1552-5279},
support = {R01 AG073282/GF/NIH HHS/United States ; RO1 NS124337-02/GF/NIH HHS/United States ; P30 AG62677/GF/NIH HHS/United States ; R01 AG068206/GF/NIH HHS/United States ; U01 AG006786/GF/NIH HHS/United States ; P50 AG016574/GF/NIH HHS/United States ; R01 AG034676/GF/NIH HHS/United States ; R37 AG011378/GF/NIH HHS/United States ; R01 AG041851/GF/NIH HHS/United States ; U19 AG063911/GF/NIH HHS/United States ; R01 NS097495/GF/NIH HHS/United States ; R01 AG056366/GF/NIH HHS/United States ; U01 NS100620/GF/NIH HHS/United States ; RF1 AG069052/GF/NIH HHS/United States ; //GHR Foundation/ ; //Elsie and Marvin Dekelboum Family Foundation/ ; //The Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic/ ; //Liston Award Family Foundation/ ; HY-202400000003953//Hanyang University/ ; //National Research Foundation/ ; RS-2023-00226494//Korean government/ ; //Mayo Foundation for Medical Education and Research/ ; //The Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program, The Schuler Foundation/ ; },
mesh = {Humans ; *Positron-Emission Tomography/methods ; *tau Proteins/metabolism ; Male ; Female ; *Alzheimer Disease/pathology/diagnostic imaging/metabolism ; Aged ; Neurofibrillary Tangles/pathology ; *Tauopathies/pathology/diagnostic imaging/metabolism ; *Brain/pathology/diagnostic imaging/metabolism ; Aged, 80 and over ; Middle Aged ; Entorhinal Cortex/pathology/diagnostic imaging/metabolism ; Carbolines ; },
abstract = {INTRODUCTION: The tau positron emission tomography (PET) overlap index (OI) has shown promise in maximizing signal-to-noise for longitudinal tau PET imaging, particularly for early tau pathology, but requires validation against neuropathology.

METHODS: Fifty-seven participants who underwent serial tau PET imaging (flortaucipir) and subsequent autopsy were included. Tau PET OI and standardized uptake value ratios (SUVRs) were compared across neuropathological diagnoses.

RESULTS: Tau PET OI showed greater concordance with neurofibrillary tangle (NFT) severity in the entorhinal cortex (a key region for Alzheimer's disease [AD] tauopathy) than SUVR, particularly in early Braak tangle stages (positivity: 52.2% for OI vs. 13.0% for SUVR). OI detected overlapping tau voxels that exhibited spatial correspondence with immunohistochemical and autoradiography measures of tau deposition across both AD and non-AD tauopathies.

DISCUSSION: These findings demonstrate the enhanced capacity of OI in serial tau PET to robustly detect early and spatially localized tau pathology, supporting its application as a sensitive imaging metric in AD and select non-AD tauopathies.},
}

Humans
*Positron-Emission Tomography/methods
*tau Proteins/metabolism
Male
Female
*Alzheimer Disease/pathology/diagnostic imaging/metabolism
Aged
Neurofibrillary Tangles/pathology
*Tauopathies/pathology/diagnostic imaging/metabolism
*Brain/pathology/diagnostic imaging/metabolism
Aged, 80 and over
Middle Aged
Entorhinal Cortex/pathology/diagnostic imaging/metabolism
Carbolines

@article {pmid41795668,
year = {2026},
author = {Ling, Y and Sun, P and Wang, C and Peng, G and Wang, Y and Zhou, X and He, Z and Liu, B and Zhang, J and Yu, J and Su, Y and Li, K and Guo, T and Luo, B},
title = {A novel eye-tracking digital marker outperforms plasma biomarkers in detecting cognitive impairment.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71253},
doi = {10.1002/alz.71253},
pmid = {41795668},
issn = {1552-5279},
support = {2022C03064//the Key Research and Development Program of Zhejiang/ ; 2025ZFJH01//the Fundamental Research for the Central Universities/ ; 2022KY067//Medical and Health Science and Technology Project of Zhejiang Province/ ; 82422027//the National Natural Science Foundation of China/ ; U24A20340//the National Natural Science Foundation of China/ ; 82171197//the National Natural Science Foundation of China/ ; 82371484//the National Natural Science Foundation of China/ ; 2023B1515020113//Guangdong Basic and Applied Basic Science Foundation for Distinguished Young Scholars/ ; },
mesh = {Humans ; *Biomarkers/blood ; *Cognitive Dysfunction/diagnosis/blood ; Male ; Female ; Amyloid beta-Peptides/blood ; Aged ; tau Proteins/blood ; *Eye-Tracking Technology ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Neuropsychological Tests ; Aged, 80 and over ; },
abstract = {INTRODUCTION: Detecting and monitoring cognitive performance in older adults is critical. In this study, we evaluated the validity of an eye-tracking tool in diagnosing cognitive impairment.

METHODS: We recruited 119 cognitively unimpaired (CU) individuals and 157 cognitively impaired (CI) patients who completed digital eye-tracking tests and cognitive scales. Of them, 154, 120, 53, and 146 underwent plasma biomarker tests, amyloid-β positron emission tomography (Aβ-PET) scans, tau-PET scans, and magnetic resonance imaging (MRI) scans. The diagnostic performance of eye-tracking markers and their relationships to Alzheimer's disease biomarkers and cognition were examined.

RESULTS: The eye-tracking panel exhibited better performance (area under the curve [AUC] = 0.865) in classifying CI from CU compared to plasma Aβ42/40 (AUC = 0.699), p-Tau217 (AUC = 0.769), p-Tau217/Aβ42 (AUC = 0.801), glial fibrillary acidic protein (GFAP; AUC = 0.804), and neurofilament light chain (NfL) (AUC = 0.826).

DISCUSSION: These findings demonstrate the validity of digital eye-tracking markers for screening patients with cognitive impairment, providing a novel digital marker for detecting cognitive decline in older adults.},
}

Humans
*Biomarkers/blood
*Cognitive Dysfunction/diagnosis/blood
Male
Female
Amyloid beta-Peptides/blood
Aged
tau Proteins/blood
*Eye-Tracking Technology
Positron-Emission Tomography
Magnetic Resonance Imaging
Neuropsychological Tests
Aged, 80 and over

@article {pmid41795661,
year = {2026},
author = {Zhang, Y and Qian, XH and Zhuang, H and Zhang, W and Hu, J and Zhao, Y and Li, Y and Jin, W and Xu, C and Meng, Z and Li, W and Chen, S and Jiang, XF and Guo, T and Li, YD and Ye, J and Liang, ZP and Li, B and Zhang, M and Tang, H and Li, Y},
title = {Dual association patterns between microglial activation and neuronal health in Alzheimer's disease: a whole-brain MRSI/PET study.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {3},
pages = {e71229},
doi = {10.1002/alz.71229},
pmid = {41795661},
issn = {1552-5279},
support = {82501770//National Natural Science Foundation of China/ ; 82571772//National Natural Science Foundation of China/ ; 82372073//National Natural Science Foundation of China/ ; 21TQ1400203//Shanghai Pilot Program for Basic Research - Shanghai Jiao Tong University/ ; //Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning/ ; YG2025ZD31//Key Program of Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University/ ; YG2025QNA45//Key Program of Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University/ ; YG2023ZD22//Key Program of Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University/ ; YG2023QNA46//Key Program of Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University/ ; 202240031//Shanghai Municipal Health Commission/ ; GCQH2023061//Guangci Clinical Technology and Innovation Program (GCTIP) of Ruijin Hospital/ ; 24dz2260100//Shanghai Key Laboratory of Child Brain and Development/ ; },
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/metabolism/pathology ; *Microglia/metabolism/pathology ; Male ; Female ; Positron-Emission Tomography ; Aged ; *Cognitive Dysfunction/diagnostic imaging/metabolism/pathology ; *Brain/diagnostic imaging/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Magnetic Resonance Spectroscopy ; *Neurons/metabolism/pathology ; Aspartic Acid/analogs & derivatives/metabolism ; Middle Aged ; },
abstract = {INTRODUCTION: Microglial activation can either support neuronal function or exacerbate damage, contributing to Alzheimer's disease (AD) progression. We investigated spatial relationships among microglial activation, neuronal health, and amyloid beta (Aβ) in the AD spectrum.

METHODS: Forty healthy controls, 37 patients with mild cognitive impairment (MCI), and 62 patients with AD underwent whole-brain high-resolution [1]H-magnetic resonance spectroscopic imaging (MRSI), [[1] [8]F]DPA-714, and [[1] [8]F]AV-45 positron emission tomography (PET). Regional and voxel-wise analyses assessed changes and associations of microglial activation with N-acetylaspartate (NAA) and Aβ.

RESULTS: MCI and AD patients showed higher microglial activation and lower NAA, correlating with cognitive decline. In controls and MCI, microglial activation correlated positively with NAA and Aβ in early amyloid-accumulating regions. Conversely, negative correlations with NAA emerged in the hippocampus in MCI and extended to temporal and occipital regions in AD.

DISCUSSION: For the first time, we identified two distinct spatial association patterns between [[1] [8]F]DPA-714 PET and NAA, shedding light on the complex interplay between neuroinflammation and neuronal health in AD.},
}

Humans
*Alzheimer Disease/diagnostic imaging/metabolism/pathology
*Microglia/metabolism/pathology
Male
Female
Positron-Emission Tomography
Aged
*Cognitive Dysfunction/diagnostic imaging/metabolism/pathology
*Brain/diagnostic imaging/metabolism/pathology
Amyloid beta-Peptides/metabolism
Magnetic Resonance Spectroscopy
*Neurons/metabolism/pathology
Aspartic Acid/analogs & derivatives/metabolism
Middle Aged

@article {pmid41795542,
year = {2026},
author = {Jing, T and Yang, L and Yuan, Z and Ling, G and Zhang, P},
title = {Deciphering the signal of metal ions: the principle, design and multi-field application of DNAzyme fluorescence sensor.},
journal = {Talanta},
volume = {305},
number = {},
pages = {129597},
doi = {10.1016/j.talanta.2026.129597},
pmid = {41795542},
issn = {1873-3573},
abstract = {Metal ion detection is the core link of ecological protection, human health, and food safety. Traditional methods (AAS, ICP-MS, etc.) are expensive and cumbersome, and it is difficult to meet the needs of rapid on-site detection. In this paper, the research progress of DNAzyme fluorescence sensors is systematically reviewed, focusing on the classification characteristics of typical DNAzymes such as 8-17 DNAzyme and GR-5 DNAzyme and their specific response mechanisms to metal ions. The detection principles of quencher mediation (such as gold nanoparticles, MOF, UCNPs, etc.), signal amplification (such as DNA walker, G-quadruplex, etc.), and multi-method combination are deeply analyzed. DNAzyme fluorescence sensors leverage the high specificity and programmability of catalytic DNA. Under optimized conditions, certain architectures achieve pM-level detection sensitivity, whereas others are robustly deployed in the nM to μM range-particularly in complex matrices. It has been widely used in biomedicine (such as tumor ion imaging, Alzheimer's disease AD brain iron ion detection), environment and resources (such as food quality detection, heavy metal pollution prevention and control), and other fields, and the actual sample detection results are in good agreement with the traditional authoritative methods. Finally, this paper reviews the existing challenges and optimization paths in terms of anti-interference in complex matrices and in vivo targeting, and provides a key reference for the innovative breakthroughs of rapid detection technology of metal ions.},
}

@article {pmid41795115,
year = {2026},
author = {Abuawad, M and Rjoub, A and Ghanim, M and ALqub, M and Dwikat, M and Al-Lahham, S and Abuabed, A and Sliman, A and Kanaaneh, A and Hanani, F},
title = {Knowledge and attitudes of clinical physicians towards Alzheimer's disease and related dementias: an observational cross-sectional study from Palestine.},
journal = {BMC medical education},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12909-026-08943-z},
pmid = {41795115},
issn = {1472-6920},
}

@article {pmid41795086,
year = {2026},
author = {Guo, HH and Su, D and Song, B and Geng, Z and Wang, L and Wang, W and Hu, W and Li, X and Li, W and Zhang, G and Fang, M and Dai, Y and Hu, P and Wu, X and Wang, K and Wei, L and , },
title = {CSF microtubule-associated protein 1 light chain 3A and 3B levels are associated with tau pathology and Alzheimer's disease risk through amyloid deposition and microglial signaling.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03758-7},
pmid = {41795086},
issn = {1742-2094},
support = {2025AHGXZK50040//Anhui Provincial Department of Education Scientific Research Project for Doctoral Students/ ; 82101498//Natural Science Foundation of China/ ; 82090034//Natural Science Foundation of China/ ; 82371201//Natural Science Foundation of China/ ; 2021kj19//2021 Youth Foundation training program of the First Affiliated Hospital of Anhui Medical University/ ; 202204295107020006//Anhui Province Clinical Medical Research Transformation Special Project/ ; XZZR202402048//Natural Science Foundation of the Xizang Autonomous Region Group Medical Aid Project to Xizang/ ; 2022zhyx-B11//Research Fund of Anhui Institute of Translational Medicine/ ; },
}

@article {pmid41794902,
year = {2026},
author = {Zhihuan, W and Furusawa-Nishii, E and Miyake, S},
title = {Unique phenotypic and T cell receptor characteristics of CD8[+] T cells accumulated in the brains of Alzheimer's disease mice.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-38351-8},
pmid = {41794902},
issn = {2045-2322},
support = {JPMJMS2024-6//the Visionary Council on the Moonshot Research and Development Program/ ; },
}

@article {pmid41794876,
year = {2026},
author = {Penning, A and Snoeck, S and Ormaechea, OR and Ayyildiz, D and Polzer, O and Buitrago-Arango, M and Capobianco, R and de Winter, F and Balusu, S and Verhaagen, J and Fitzsimons, CP and d'Ydewalle, C and Lucassen, PJ and Moechars, D and Zhou, L and Salta, E},
title = {microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients.},
journal = {Acta neuropathologica communications},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40478-026-02228-8},
pmid = {41794876},
issn = {2051-5960},
}

@article {pmid41794870,
year = {2026},
author = {Salari, MT and Gholami, K and Khani, L and Ahmadnia, H and Iranshahy, M and Iranshahi, M and Majd, MT and Behnam-Rassouli, M and Yazarlu, O and Hasanpour, M},
title = {Neuroprotective effects of Urolithin A and B in an intracerebroventricular streptozotocin-induced Alzheimer's-like model in rats.},
journal = {BMC pharmacology & toxicology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40360-026-01118-y},
pmid = {41794870},
issn = {2050-6511},
support = {4020387//Mashhad University of Medical Sciences/ ; },
}

@article {pmid41794848,
year = {2026},
author = {Ben-Jaafar, A and Sinha, A and Nkrumah-Boateng, PA and Roy, S and Sanker, V and Mohamed, S and Sarfo-Adu, F and Ali, SH and Wireko, AA},
title = {Artificial intelligence-based biomarkers for the diagnosis and treatment of neurological conditions: a narrative review.},
journal = {Molecular brain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13041-026-01287-1},
pmid = {41794848},
issn = {1756-6606},
abstract = {Artificial intelligence (AI) is transforming biomarker discovery in neurology by overcoming key limitations of conventional approaches that are often slow, reductionist, and unable to integrate complex multimodal data. In this narrative review, we searched the data bases; PubMed, Scopus, IEEE Xplore, CINAHL, Embase and the Cochrane Library from inception to 2025 to evaluate how AI supports biomarker identification, diagnosis, prognostication, and treatment stratification across neurovascular, neurodegenerative, neuro-oncological and seizure disorders. Evidence demonstrates that AI-driven imaging and multi-omics biomarkers can detect disease earlier, improve prediction accuracy, and support personalised care. For example, AI models improve stroke outcome prediction beyond conventional scores, identify intracranial aneurysms with sensitivities exceeding 90%, predict conversion from mild cognitive impairment to Alzheimer's disease with accuracies approaching 85-90%, and extract radiogenomic biomarkers in gliomas that outperform traditional diagnostic strategies. However, real-world translation remains constrained by dataset bias, limited external validation, interpretability challenges, and gaps in generalisability, particularly in underrepresented populations. Overall, AI-driven biomarker discovery offers a powerful pathway toward precision neurology, with the greatest impact expected when technical innovation is paired with robust clinical validation, regulatory integration, and equitable data representation.},
}

@article {pmid41794826,
year = {2026},
author = {Melgosa-Ecenarro, L and Radulescu, CI and Doostdar, N and Airey, J and Chaloner, FA and Zabouri, N and Pedretti, G and Osso, F and Garrido Perez, L and Pilch, KS and Wang, X and Mallach, A and Sadeh, S and Jackson, J and Matthews, PM and Barnes, SJ},
title = {Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-69866-3},
pmid = {41794826},
issn = {2041-1723},
support = {A2022030S//BrightFocus Foundation (BrightFocus)/ ; },
abstract = {Synaptic dysfunction in Alzheimer's disease (AD) may drive synapse loss and cognitive impairment. Whether AD-related synaptic pathophysiology occurs globally, or in specific synapses, is unclear. We investigate in vivo AD-related synaptic dysfunction during early-stage amyloidosis in App[NL-G-F] mice. We find reduced presynaptic GABAergic proteins at c-Fos-positive excitatory neurons and increased calcium-mediated activity at excitatory and inhibitory neuronal assemblies. In vivo synaptic structure/function imaging finds reduced density and calcium-mediated activity of GABAergic axonal boutons. Rather than occurring globally, reduced synaptic activity is focused at GABAergic boutons strongly coupled to population activity in the amyloid microenvironment. The selective weakening of population-coupled synaptic activity also occurs in excitatory dendritic spines. Spatial transcriptomics finds parvalbumin-positive inhibitory neurons show differential gene expression associated with downregulated GABAergic synaptic transmission at early stages. We propose that early-stage AD-related synaptic pathophysiology is focused at population-coupled synapses, with molecular measures implicating abnormal synaptic processing as an early-stage feature in parvalbumin-positive interneurons.},
}

@article {pmid41794745,
year = {2026},
author = {Yang, J and Ding, H and Amini, S and Hao, B and Karjadi, C and Au, R and Paschalidis, IC},
title = {Resource-stratified machine learning framework for cognitive status classification and mild cognitive impairment to dementia progression prediction.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02006-7},
pmid = {41794745},
issn = {1758-9193},
support = {AG062109/AG/NIA NIH HHS/United States ; CCF-2200052//National Science Foundation, United States/ ; DEB-2433726//Office of Inspector General/ ; UL54 TR00413/GF/NIH HHS/United States ; },
}

@article {pmid41794636,
year = {2026},
author = {Li, J and Wang, C and Zhang, JH and Cai, JM and Cao, YP and Sun, XJ},
title = {Retraction notice to "Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress" [Brain Res. 1328 (2010) 152-161].},
journal = {Brain research},
volume = {},
number = {},
pages = {150251},
doi = {10.1016/j.brainres.2026.150251},
pmid = {41794636},
issn = {1872-6240},
}

@article {pmid41794294,
year = {2026},
author = {Jiang, Z and Saleem, K and Fisher, E and Li, L and Yan, Z and Feng, J},
title = {SGK1 inhibition restores excitability of cortical neurons derived from Alzheimer's disease patients.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107345},
doi = {10.1016/j.nbd.2026.107345},
pmid = {41794294},
issn = {1095-953X},
abstract = {The vast majority of Alzheimer's disease (AD) cases are sporadic, without a clear etiology. We have previously found increased expression of Serum and Glucocorticoid-regulated Kinase 1 (SGK1) in mouse models of dementia, postmortem cortical tissues and induced pluripotent stem cells (iPSCs)-derived cortical neurons from patients with sporadic AD (sAD). SGK1 is induced by a variety of cellular stress. The physiological consequences of elevated SGK1 in sAD is unclear. Here, we differentiated iPSCs from four sAD patients and four age- and sex-matched healthy controls into electrophysiologically mature cortical neurons with prolonged culture for more than 100 days. The sAD cortical neurons exhibited significant reductions in voltage-gated Na[+] currents, amplitudes of evoked action potentials, and frequencies of spontaneous excitatory postsynaptic currents and spontaneous action potentials. Application of a selective inhibitor of SGK1 reversed all these phenotypes in sAD neurons without affecting control neurons. The SGK1-dependent hypoexcitability suggests that a convergent and inborn mechanism attenuates neuronal communications despite different genetic background of the sAD patients. Their iPSC-derived cortical neurons have captured the defective neurotransmission, which underlies cognitive and memory symptoms of AD, many decades before clinical manifestations. The study offers a new pathway to restore synaptic transmission in AD.},
}

@article {pmid41794249,
year = {2026},
author = {Li, QM and Zhang-Yang, QQ and Tan, YY and Wu, XL and Zha, XQ and Shang, ZZ and Luo, JP and Zhang, FY},
title = {Dendrobium huoshanense stem polysaccharide protects against Alzheimer's disease by modulating SCFAs/GLP-1 axis-mediated neuroinflammation suppression.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {151235},
doi = {10.1016/j.ijbiomac.2026.151235},
pmid = {41794249},
issn = {1879-0003},
abstract = {Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. The stem of Dendrobium huoshanense is a traditional medicinal food. This study aimed to investigate the effect of cultivated D. huoshanense stem polysaccharide (cDHPS) on AD and elucidate its mechanisms using an Aβ1-42-induced AD mouse model. Results showed that cDHPS significantly improved the cognitive dysfunction and ameliorated the hippocampal neuronal injury of AD mice. Meanwhile, cDHPS effectively alleviated the neuroinflammation of AD mice not only by decreasing the expression of caspase-1, NOD-like receptor family pyrin domain-containing 3 (NLRP3), and apoptosis-associated speck-like protein containing a CARD (ASC), as well as their downstream inflammatory cytokines, but also by inhibiting the activation of microglia and astrocytes. Furthermore, the levels of glucagon-like peptide-1 (GLP-1) in the hippocampus, plasma, and intestine of AD mice were markedly elevated by cDHPS, along with an increase in intestinal short-chain fatty acids (SCFAs) levels. However, the treatment of exendin 9-39, a GLP-1 receptor antagonist, weakened the protective effect of cDHPS against AD, and the depletion of SCFAs reversed the beneficial effects of cDHPS on cognitive dysfunction, hippocampal neuronal injury, neuroinflammation, and GLP-1 secretion in AD mice. These results suggest that cDHPS could protect against AD by modulating the SCFAs/GLP-1 axis-mediated neuroinflammation suppression.},
}

@article {pmid41794188,
year = {2026},
author = {Marzetti, E and Di Lorenzo, R and Calvani, R and Coelho-Júnior, HJ and D'Argento, E and Pesce, V and Landi, F and Bucci, C and Guerra, F and Picca, A},
title = {Mitochondrial quality in aging and neurodegeneration: The emerging role of mitochondria-derived vesicles.},
journal = {Mechanisms of ageing and development},
volume = {},
number = {},
pages = {112167},
doi = {10.1016/j.mad.2026.112167},
pmid = {41794188},
issn = {1872-6216},
abstract = {Mitochondria are central to cellular energy metabolism, redox balance, and signaling, and their integrity is maintained by a multilayered mitochondrial quality control (MQC) system. This system includes proteostasis, dynamics, biogenesis, and mitophagy, which together repair or remove damaged organelles. Mitochondria-derived vesicles (MDVs) have emerged as an additional MQC component. MDVs are small vesicles that bud from mitochondria and selectively transport damaged mitochondrial proteins, lipids, and nucleic acids to endolysosomal compartments or other intracellular destinations, enabling rapid and localized responses to mitochondrial stress. Acting upstream of or in parallel with mitophagy, MDVs can delay irreversible mitochondrial damage and help preserve cellular homeostasis. Aging and age-associated disorders are characterized by progressive mitochondrial dysfunction and chronic inflammation. Age-related changes in intracellular trafficking, lysosomal function, and vesicle dynamics may impair MDV formation, cargo selection, and targeting. Under conditions of defective degradation, mitochondrial components may also appear in extracellular vesicles, potentially contributing to altered intercellular signaling and inflammation. In the nervous system, where energetic demands are high and mitochondrial turnover requires tight regulation, such alterations may be especially harmful. This review summarizes MQC mechanisms in neurons, with a focus on MDVs, their dysregulation during aging and neurodegeneration, and implications for biomarkers and therapeutic strategies.},
}

@article {pmid41793956,
year = {2026},
author = {Wu, AH and Wu, J and Tseng, C and Darst, BF and Park, SY and Stram, DO and Larson, T and Fruin, S and Setiawan, VW and Yu, X and Wilkens, LR and Hu, H and Haiman, C and Ritz, B and Crimmins, EM and Lim, U and Cheng, I and Marchand, LL},
title = {Racial and ethnic differences in the impact of air pollution on the risk of Alzheimer's disease and related dementias in the Multiethnic Cohort Study.},
journal = {Environment international},
volume = {209},
number = {},
pages = {110169},
doi = {10.1016/j.envint.2026.110169},
pmid = {41793956},
issn = {1873-6750},
abstract = {BACKGROUND AND OBJECTIVES: Meta-analysis results, based largely among Whites, suggested that fine particulate matter (PM2.5) exposure increases the risk of clinical dementia. This study investigated the association of air pollution and incidence of Alzheimer's disease and related dementias (ADRD) by race and ethnicity.

METHODS: We investigated incidence of AD (n = 4,010) and other dementia (n = 4,971) among 44,954 California Multiethnic Cohort (MEC) participants (28% African American, 14% Japanese American, 44% Latino, 14% White adults) who were enrolled in the fee-for-service component of Medicare (2001-2016). We used Cox proportional hazards regression to examine associations between exposure to PM, airport-related ultrafine particles (aUFP) and gaseous pollutants and incidence of AD, other dementia, and ADRD in a minimally- and fully-adjusted model, considering 12 established ADRD risk factors. We conducted stratified analyses to examine associations by sex, and race/ethnicity.

RESULTS: ADRD incidence was associated with PM2.5 (per 2 µg/m[3]), airport-related UFP (aUFP, per 4400 particles/cm[3]) and nitrogen dioxide (NO2, per 10 µg/m[3]) with hazard ratios (HRs, 95%CI), respectively, of 1.04 (1.02-1.06), 1.03 (1.01-1.05) and 1.09 (1.06-1.12). The AD-associations with PM2.5 and NO2, were stronger than the corresponding associations with other dementia (Pheterogeneity ≤ 0.003). Similar patterns of results were observed by sex and across race and ethnicity. Statistically significant findings for ADRD with PM2.5, aUFP and NO2 were observed among African American (respective HRs 1.03, 1.04, 1.09), and Latino and White participants for NO2 (HR 1.10, 1.08). Results in all and African American participants remained statistically significant in fully-adjusted models. Although the effect of PM2.5 was diluted in a co-pollutant with NO2, both PM2.5 and aUFP were significantly associated with ADRD incidence in a co-pollutant model, and NO2 and aUFP (but not PM2.5) remained associated in a multipollutant model. We did not observe consistent modifying effects for any of the 12 established ADRD risk factors.

CONCLUSIONS: In this multiethnic population, incidence of ADRD increased with exposures to PM2.5, aUFP, and NO2 in all subjects and this pattern was most prominent among African American adults. These results emphasize that ADRD prevention should include not only individual-level factors but also population-wide policies and regulation to curb air pollution.},
}

@article {pmid41793523,
year = {2026},
author = {Xiong, R and Liu, P and Wang, L and Zhang, S and Liu, H and Rong, C and Kehriman, N and Wang, J and Wang, J and Lai, X and Tang, Y},
title = {Elucidating the pharmacological mechanism of Yangming-Kaixin-Yizhi formula in inhibiting neuronal ferroptosis via Nrf2 in Alzheimer's disease: a study combining network pharmacology, transcriptomics, and experimental validation.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41793523},
issn = {1573-7365},
support = {82405150//National Natural Science Foundation of China/ ; CSTB2025NSCQ-GPX0082//Natural Science Foundation of Chongqing, China/ ; 2024ZYQN017//Joint Project of Chongqing Health Commission and Science and Technology Bureau/ ; GXHC-MBTCM-01//Open Project of Guangxi Health Commission Guangxi Key Laboratory of Molecular Biology of Preventive Medicine of Traditional Chinese Medicine/ ; ZYJCLLYB-18//Open Fund of High-level Key Discipline of Basic Theory of TCM of the State Administration of Traditional Chinese Medicine, Anhui University of Chinese Medicine/ ; 2025ZNSFSC0740//Sichuan Provincial Science and Technology Support Program/ ; },
mesh = {Animals ; *Ferroptosis/drug effects ; *Alzheimer Disease/drug therapy/metabolism/genetics ; Mice ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *NF-E2-Related Factor 2/metabolism/genetics ; *Neurons/drug effects/metabolism ; Network Pharmacology/methods ; Mice, Transgenic ; Transcriptome/drug effects ; Male ; Hippocampus/drug effects/metabolism ; Reactive Oxygen Species/metabolism ; },
abstract = {Ferroptosis is considered to be an important pathological driver of Alzheimer's disease (AD), and inhibiting neuronal ferroptosis shows a significant AD improvement effect. Yangming-Kaixin-Yizhi formula (YKY), a traditional Chinese medicine (TCM) formula, has been used for the treatment of forgetfulness for hundreds of years, but its mechanisms remain unclear. This study aimed to delineate the herb-component-target network of YKY in regulating ferroptosis for the treatment of AD, providing modern scientific basis for the traditional use of YKY. After 3×Tg-AD mice were orally treated with YKY for 11 weeks, the learning and memory ability of the mice was evaluated by Morris water maze, and hippocampal neuron loss was observed by hematoxylin-eosin (HE) staining. Transcriptomics and network pharmacology were used to analyze the underlying pharmacological mechanisms. Perls staining and immunofluorescence were used to observe brain iron deposition and hippocampal neuronal ferroptosis, respectively. The effects of YKY on iron deposition, reactive oxygen species (ROS) and lipid peroxidation in HT22 cells were detected by FerroOrange, DCFH-DA and BODIPY [581/591] C11 fluorescent probes, respectively. Western blot was used to detect the expression of Nrf2 and ferroptosis-related proteins to verify the pharmacological mechanism of YKY. YKY significantly improved the learning and memory ability and neuronal loss in 3×Tg-AD mice, and transcriptome and network pharmacology analysis suggested that its pharmacological mechanism may be related to regulation of iron metabolism, ferroptosis and Nrf2 regulated gene transcription. YKY significantly reduced intracellular iron deposition, improved cell viability, reduced ROS and lipid peroxidation levels, promoted the protein expression of Nrf2 and its downstream SLC7A11, GPX4 and FTH1, and inhibited the expression of TFR1 and NCOA4 proteins in 3×Tg-AD mice and RSL3-mediated HT22 cells. YKY may improve AD by targeting Nrf2 to inhibit neuronal ferroptosis, which provides modern scientific evidence for the use of YKY in TCM to treat disorders associated with memory loss.},
}

Animals
*Ferroptosis/drug effects
*Alzheimer Disease/drug therapy/metabolism/genetics
Mice
*Drugs, Chinese Herbal/pharmacology/therapeutic use
*NF-E2-Related Factor 2/metabolism/genetics
*Neurons/drug effects/metabolism
Network Pharmacology/methods
Mice, Transgenic
Transcriptome/drug effects
Male
Hippocampus/drug effects/metabolism
Reactive Oxygen Species/metabolism

@article {pmid41793494,
year = {2026},
author = {Ouyang, Z and Liu, F and Lu, Q and Wang, Y and Shao, N and Liu, H and Cai, B},
title = {Aloe-emodin inhibits p38 MAPK pathway in Alzheimer's disease treatment: a network pharmacology and experimental verification.},
journal = {Journal of molecular histology},
volume = {57},
number = {2},
pages = {},
pmid = {41793494},
issn = {1567-2387},
support = {No.2024AH050951//Scientific Research Foundation of the Education Department of Anhui Province/ ; No.2023xscx096//Postgraduate Quality Engineering Project in Anhui Province/ ; NO. 82374553//National Natural Science Foundation of China/ ; No. 2308085MH295//Natural Science Foundation of Anhui province/ ; },
mesh = {*Alzheimer Disease/drug therapy/metabolism ; *Anthraquinones/pharmacology/chemistry/therapeutic use ; Humans ; Amyloid beta-Peptides/metabolism ; *Network Pharmacology/methods ; Molecular Docking Simulation ; *p38 Mitogen-Activated Protein Kinases/metabolism/antagonists & inhibitors ; Phosphorylation/drug effects ; *MAP Kinase Signaling System/drug effects ; tau Proteins/metabolism ; Peptide Fragments/toxicity ; Cell Survival/drug effects ; Neuroprotective Agents/pharmacology ; Animals ; },
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by abnormal amyloid-β protein (Aβ) deposition and tau protein hyperphosphorylation (p-tau), yet effective therapeutics remain scarce. Aloe emodin (AE) is a natural anthraquinone derivative that demonstrates neuroprotective effects. However, its specific therapeutic efficacy and functional mechanism are not fully elucidated. To address this, we investigated AE's mechanism in AD treatment using a network pharmacology approach. This analysis revealed that 83 common targets shared by AE and AD, enriched in processes such as apoptosis and protein phosphorylation. Mitogen-activated protein kinase 14 (MAPK14, also known as p38) was identified as a key target. KEGG pathway analysis further confirmed that the key mechanism of AE in AD treatment was mediated by the MAPK signaling pathway. Subsequent molecular docking and dynamics simulations demonstrated that the AE-p38 complex exhibited strong binding affinity and high stability. Building on these predictions, in vitro studies confirmed that AE enhanced cell viability and modulated the MAPK pathway. Critically, p38-specific inhibition experiments demonstrated that AE alleviated Aβ accumulation and tau hyperphosphorylation through inhibiting p38. In conclusion, this study demonstrates that AE protects against Aβ25-35-induced neurotoxicity in HT22 cells, primarily by inhibiting the p38 MAPK signaling pathway.},
}

*Alzheimer Disease/drug therapy/metabolism
*Anthraquinones/pharmacology/chemistry/therapeutic use
Humans
Amyloid beta-Peptides/metabolism
*Network Pharmacology/methods
Molecular Docking Simulation
*p38 Mitogen-Activated Protein Kinases/metabolism/antagonists & inhibitors
Phosphorylation/drug effects
*MAP Kinase Signaling System/drug effects
tau Proteins/metabolism
Peptide Fragments/toxicity
Cell Survival/drug effects
Neuroprotective Agents/pharmacology
Animals

@article {pmid41793299,
year = {2026},
author = {Kao, HS and Aguilera, J and Hung, CC and Kiani, S and Nava, A and Montalvo-Liendo, N},
title = {Lessons Learned in a Feasibility Study With U.S. Women Caregivers of Mexican Origin.},
journal = {Health promotion practice},
volume = {},
number = {},
pages = {15248399261426007},
doi = {10.1177/15248399261426007},
pmid = {41793299},
issn = {1552-6372},
abstract = {With the rapidly aging Hispanic/Latino population in the United States and the traditional caregiving roles of women in this culture, it is critical to study caregiving stress in the largest yet understudied subgroup-women caregivers of Mexican origin. This descriptive feasibility study aimed to adapt a research protocol to examine the impact of long-term caregiving stress on coronary heart disease risk among women caregivers of Mexican origin, using the allostatic load model and the Framingham Risk Score. A purposive sample of 20 women providing family care to a dependent older relative for at least 24 hours per week over the past 6 months was recruited through community networks, home health care agencies, promotoras, the local chapter of the Alzheimer's Association, and hospital outpatient services in a U.S.-Mexico border city. Multiple approaches were employed, including structured interviews and the collection of biological samples. Key adjustments included refining terminology to align with participants' preferences, managing complex data collection, and adjusting recruitment criteria to reflect cultural norms. COVID-19-related delays necessitated further adaptations, including proactive licensing management and alternative recruitment strategies. Inclusion and exclusion criteria were revised multiple times to better reflect family caregiving dynamics, ensuring continuity despite staff turnover and rising costs due to the study's extended duration and inflation. By addressing these challenges, we laid the groundwork for research on long-term caregiving among women of Mexican origin. Future research will focus on developing preventive interventions to reduce caregiving stress and coronary heart disease risk, ultimately supporting aging-in-place for dependent older adults in their care.},
}

@article {pmid41793281,
year = {2026},
author = {Nafikov, RA and Sohi, HK and Nato, AQ and Horimoto, AR and Day, TRC and Bird, TD and DeStefano, AL and Blue, EE and Wijsman, EM},
title = {Variant Prioritization by Pedigree-Based Haplotyping.},
journal = {Genetic epidemiology},
volume = {50},
number = {3},
pages = {e70039},
doi = {10.1002/gepi.70039},
pmid = {41793281},
issn = {1098-2272},
support = {U01 AG058589/AG/NIA NIH HHS/United States ; U01 AG049507/AG/NIA NIH HHS/United States ; T32 AG052354/AG/NIA NIH HHS/United States ; T32 GM007454/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; *Haplotypes ; *Pedigree ; Genetic Predisposition to Disease ; Alzheimer Disease/genetics ; Gene Frequency ; Polymorphism, Single Nucleotide ; Whole Genome Sequencing ; Male ; Computer Simulation ; Genetic Variation ; Models, Genetic ; Alleles ; Female ; },
abstract = {Whole genome sequence (WGS) data provides opportunities for comprehensive evaluation of variants that may influence complex traits. However, prioritizing the large number of variants, particularly those in non-coding regions, is a challenge. Here we present an approach that uses pedigree-based haplotyping to identify the risk haplotype and resulting set of prioritized variants in a region of interest (ROI) defined by identity-by-descent (IBD) sharing among familial cases. The approach is applicable for use in both a full range of pedigree sizes and for the full allele frequency spectrum of variants without the need for a large reference sample. By determining haplotype sharing among individuals with WGS data, we demonstrate the ability to accurately identify a risk haplotype and a strongly reduced list of potential risk alleles for a trait of interest along with the cases who carry the risk haplotype. This is important in the context of complex traits where the disease may be etiologically heterogeneous even within a single pedigree. Application to both simulated and real Alzheimer's disease family data shows that the approach leads to accurate risk-haplotype identification with marked reduction in the number of potential trait-associated variants. Simulation also shows that the approach provides accurate risk haplotypes in ROIs.},
}

Humans
*Haplotypes
*Pedigree
Genetic Predisposition to Disease
Alzheimer Disease/genetics
Gene Frequency
Polymorphism, Single Nucleotide
Whole Genome Sequencing
Male
Computer Simulation
Genetic Variation
Models, Genetic
Alleles
Female

@article {pmid41793191,
year = {2026},
author = {Barry-Simonnet, C and Crouzier, L and Moujellil-Legagneur, T and Chaieb-Errass, H and Idres, YA and Ferrare, K and Rolland, M and Cazals, G and Poucheret, P and Maurice, T and Tousch, D},
title = {Xanthatin-13-(Pyrrolidine-2-Carboxylic Acid), a Sesquiterpene Lactone Isolated From Burdock Leaf, Attenuated Aβ25-35 Toxicity and Memory Deficits in a Pharmacological Mouse Model of Alzheimer's Disease.},
journal = {Phytotherapy research : PTR},
volume = {},
number = {},
pages = {},
doi = {10.1002/ptr.70294},
pmid = {41793191},
issn = {1099-1573},
support = {Soutien à la Recherche 2023 Accélérateur d'Innovation//Université de Montpellier/ ; },
abstract = {Alzheimer's disease (AD) is a severe form of dementia, which occurrence increases with age and lifestyle conditions. It is characterized by amyloid protein accumulation forming senile plaques, hyperphosphorylated tau protein forming neurofibrillary tangles, neuroinflammation, and oxidative stress, leading to synapse loss and cell death. Pharmacological alternatives to conventional treatments include alkaloids with anti-inflammatory and antioxidant properties. Sesquiterpene lactones, such as Xanthatin-13-(pyrrolidine-2-carboxylic acid) (XPc) from burdock leaf, show promise due to their antioxidant activity targeting glucose-6-phosphate dehydrogenase. This study evaluated XPc's protective effects in vivo using Aβ25-35-treated mice, a pharmacological AD model, and explores its synergistic potential with neuroprotective agents like TSPO activators or sigma-1 receptor agonists. Mice were administered Aβ25-35 peptide (9 nmol ICV) and XPc (0.3-3 mg/kg) daily for 4 days. Behavioral tests assessed memory deficits and anxiety. Post-sacrifice, brains were analyzed for neuroinflammation and oxidative stress markers. Combination studies involved XPc with the TSPO activator PK11195 or the sigma-1 receptor agonist PRE-084, with memory evaluated in two behavioral tests. Combination indices were calculated to assess synergy. XPc (1-3 mg/kg) prevented Aβ25-35-induced memory impairments and anxiety. It reduced astroglial reaction, blocked microglial activation, and confirmed antioxidant activity by lowering lipid peroxidation and protein nitrosylation. Combinations with PK11195 or PRE-084 showed synergistic protection in memory tests. XPc is a potent neuroprotective agent against AD-like toxicity in this murine model, effective alone or in synergistic combinations with other drugs.},
}

@article {pmid41793080,
year = {2026},
author = {Inagawa, S and Inagawa, Y and Tsugawa, A and Takenoshita, N and Saito, K and Ishii, K and Kasuga, K and Ikeuchi, T and Shimizu, S},
title = {Eligibility for Anti-Amyloid-β Monoclonal Antibodies in Patients With Primary Progressive Aphasia due to Alzheimer's Disease in Japan.},
journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society},
volume = {26},
number = {2},
pages = {e70152},
doi = {10.1111/psyg.70152},
pmid = {41793080},
issn = {1479-8301},
mesh = {Humans ; *Alzheimer Disease/complications/drug therapy ; Male ; Female ; *Aphasia, Primary Progressive/drug therapy/etiology/diagnosis ; Aged ; Japan ; *Amyloid beta-Peptides/immunology ; Tomography, Emission-Computed, Single-Photon ; *Antibodies, Monoclonal/therapeutic use ; Biomarkers/cerebrospinal fluid ; Neuropsychological Tests ; Positron-Emission Tomography ; Middle Aged ; Magnetic Resonance Imaging ; Aged, 80 and over ; Brain/diagnostic imaging ; },
abstract = {BACKGROUND: Primary progressive aphasia (PPA) is a clinical syndrome characterized by progressive language impairment. The logopenic variant (lvPPA) is frequently associated with Alzheimer's disease (AD) pathology. With the approval of anti-amyloid-β monoclonal antibodies, such as lecanemab and donanemab, for the treatment of AD, accurately differentiating lvPPA due to AD (lvAD) from the other PPA variants has become highly important.

METHODS: Thirteen patients with PPA who underwent cognitive testing, including the Standard Language Test of Aphasia (SLTA), brain magnetic resonance imaging, single-photon emission computed tomography (SPECT), cerebrospinal fluid (CSF) biomarker analysis, and amyloid positron emission tomography (PET) imaging were enrolled in this study. Patients were classified into the lvPPA, semantic variant PPA (svPPA), and nonfluent/agrammatic variant PPA (nfaPPA) groups based on the results of clinical and neuropsychological assessments. We determined the proportion of PPA patients in each group who met the optimal use guidelines for anti-amyloid monoclonal antibody therapy.

RESULTS: Six (86%) of the 7 lvPPA patients were amyloid positive (A+), and 5 (71%) were eligible for lecanemab or donanemab. In most lvPPA patients, SPECT displayed an AD-typical pattern of hypoperfusion in the bilateral temporoparietal regions, posterior cingulate gyrus, and precuneus. One lvPPA patient was negative for AD biomarkers and demonstrated an atypical perfusion pattern for AD, and was subsequently rediagnosed as having frontotemporal lobar degeneration.

CONCLUSIONS: These results suggest that SPECT may play a supportive role in differentiating lvAD from PPA. In the current clinical era of anti-amyloid-β monoclonal antibody therapy, accurate identification of lvAD among patients with language-predominant symptoms is increasingly important. Larger studies should be performed in the near future to validate these findings.},
}

Humans
*Alzheimer Disease/complications/drug therapy
Male
Female
*Aphasia, Primary Progressive/drug therapy/etiology/diagnosis
Aged
Japan
*Amyloid beta-Peptides/immunology
Tomography, Emission-Computed, Single-Photon
*Antibodies, Monoclonal/therapeutic use
Biomarkers/cerebrospinal fluid
Neuropsychological Tests
Positron-Emission Tomography
Middle Aged
Magnetic Resonance Imaging
Aged, 80 and over
Brain/diagnostic imaging

@article {pmid41792880,
year = {2026},
author = {Zahran, A and Abu-Khazneh, O and Bdair, M and Hajjeh, O and AbuBaha, M and Shehadeh, W and Awashra, A and Alazizi, I and Fuqha, R and Saife, S and Fuqha, H and Milhem, F and Hamshary, H and Abuzahra, D and Shuaib, U},
title = {Glymphatic System Dysfunction in Central Nervous System Diseases.},
journal = {CNS neuroscience & therapeutics},
volume = {32},
number = {3},
pages = {e70810},
doi = {10.1002/cns.70810},
pmid = {41792880},
issn = {1755-5949},
abstract = {BACKGROUND: The glymphatic system is a perivascular cerebrospinal fluid (CSF)-interstitial fluid (ISF) exchange pathway that supports brain homeostasis by clearing metabolic waste and neurotoxic proteins. Across central nervous system diseases, converging evidence indicates that glymphatic dysfunction represents a shared pathophysiological axis linking vascular, astroglial, inflammatory, and sleep-related disturbances to impaired solute clearance.

RESULTS AND CONCLUSION: In this review, we synthesize mechanistic and clinical evidence for glymphatic impairment in acute brain injury (ischemic and hemorrhagic stroke, traumatic brain injury) and chronic neurological disorders (Alzheimer's disease, Parkinson's disease, cerebral small vessel disease, multiple sclerosis, idiopathic normal pressure hydrocephalus, idiopathic intracranial hypertension, epilepsy, and headache disorders). Major mechanisms include (i) aquaporin-4 (AQP4) depolarization/mislocalization at astrocytic endfeet, reducing perivascular water transport; (ii) perivascular space compression or obstruction from cytotoxic/vasogenic edema, blood-derived products, protein aggregates, or altered extracellular matrix; (iii) loss of arterial pulsatility and vascular stiffening, weakening the driving forces for convective exchange; (iv) blood-brain barrier disruption and neuroinflammation, which remodel perivascular architecture and amplify clearance failure; and (v) sleep and autonomic dysregulation, including altered noradrenergic tone, which suppresses glymphatic activity during periods when clearance is normally maximal. Clinically, glymphatic dysfunction can be probed using diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS), contrast-enhanced MRI approaches, and structural surrogates such as enlarged perivascular spaces, with emerging associations to cognition, mood, and disease severity. Finally, we discuss translational strategies aimed at restoring clearance, including sleep/circadian optimization, vascular risk control, anti-inflammatory approaches, AQP4- and TRPV4-oriented targets, and neuromodulation. Mechanism-guided, standardized imaging and longitudinal interventional studies are needed to establish glymphatic biomarkers as actionable therapeutic and prognostic tools.},
}

@article {pmid41792827,
year = {2026},
author = {Mastrangelo, A and Caldera, S and Baiardi, S and Magliocchetti, F and Mammana, A and Testa, M and Ranieri, A and Ruggeri, E and Bentivenga, GM and Mastrangelo, V and Mometto, N and Ferri, C and Marti, A and Santangelo, M and Longoni, M and Mazzoli, S and Chiari, A and Biscetti, L and Capellari, S and Parchi, P},
title = {Prevalence and clinical effects of Lewy Body pathology in non-prion rapidly progressive dementias: a retrospective cohort study.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02004-9},
pmid = {41792827},
issn = {1758-9193},
support = {MNESYS (PE0000006)//Ministero dell'Università e della Ricerca/ ; RF-2021-12374386//Ministero della Salute/ ; },
}

@article {pmid41792667,
year = {2026},
author = {Kiene, F and Notbohm, A and Roheger, M and Duning, T and Hildebrandt, H},
title = {Cognitive tests distinguish biomarker-verified early Alzheimer's disease from other patients.},
journal = {BMC neurology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12883-026-04742-7},
pmid = {41792667},
issn = {1471-2377},
}

@article {pmid41792456,
year = {2026},
author = {Abdulkhaliq, AA and Alasiri, G and Kim, B and Khan, J and Ajoolabady, A and Yousof, SM and Ren, J and Tuomilehto, J and Borai, A and Alrfaei, BM and Pratico, D},
title = {TREM2 in neurodegeneration and diseases.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41792456},
issn = {1476-5578},
abstract = {Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell surface transmembrane receptor from the TREM receptor family, predominantly expressed on the microglia in the central nervous system (CNS). TREM2-initiated signaling plays a crucial role in regulating neuroinflammation and neurodegeneration, particularly in the context of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), through the activation of downstream signaling pathways and transcriptional regulation of relevant genes. In this review, we aim to provide a concise review of the role and mechanistic implications of TREM2 in neurodegeneration and neuroinflammation, with a specific focus on AD and PD. We will discuss the most recent preclinical studies to highlight current advancements in the field. This review is intended to support both basic researchers and clinicians by enhancing their understanding of microglial function in the pathophysiology of AD and PD, as well as its role in neuroinflammation and neurodegeneration. Ultimately, we hope this contribution will pave the way for new discoveries and the development of potential therapeutic interventions.},
}

@article {pmid41792386,
year = {2026},
author = {Kaczmarek, B and Ilkowska-Adamczewska, Z and Remlinger-Molenda, A and Kaluzniak-Szymanowska, A and Stachnik, K and Wieczorowska-Tobis, K and Tobis, S},
title = {The use of screening tests in panel studies to monitor cognitive functioning in senior participation programme groups using ACE-III and M-ACE.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42595-9},
pmid = {41792386},
issn = {2045-2322},
}

@article {pmid41792369,
year = {2026},
author = {Huang, S and Zhang, T and Wang, Y and Du, H and He, J and Zeng, H and Ma, L and Deng, D and Zhou, Y and Liu, S and Zhao, W and Yang, X and Han, L and Zhao, S and Shu, S and Yao, S and Zhong, Q and Chen, X and Wang, J},
title = {Interaction between transient receptor potential vanilloid 4 and glutamate NMDA receptor subunit 1 mediates endoplasmic reticulum stress and neuroinflammation in postoperative delirium.},
journal = {Molecular biomedicine},
volume = {7},
number = {1},
pages = {},
pmid = {41792369},
issn = {2662-8651},
support = {82471504//National Natural Science Foundation of China/ ; 32271148//National Natural Science Foundation of China/ ; 82471251//National Natural Science Foundation of China/ ; 82201350//National Natural Science Foundation of China/ ; 82401847//National Natural Science Foundation of China/ ; 23SWAQ24//Biosecurity Research Project/ ; 2024MZFS002//Research Grant of Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education/ ; },
abstract = {Postoperative delirium (POD) is a serious and prevalent neurocognitive complication that poses a major clinical challenge because its mechanism is unclear. This study identifies a pathogenic pathway centred on the direct interaction between transient receptor potential vanilloid 4 (TRPV4) and the essential N-methyl-D-aspartate receptor (NMDAR) subunit GluN1. Using a murine POD model, the neuron-centric glutamatergic dysfunction in the hippocampus was initially confirmed through ex vivo metabolic kinetic analysis. Transcriptomic analysis revealed upregulation of Trpv4, predominantly in neurons. Co-immunoprecipitation coupled with mass spectrometry revealed that TRPV4 directly interacts with GluN1. This enhanced TRPV4-GluN1 coupling promoted GluN1 phosphorylation at serine 896 and hyperactivated NMDAR signalling. We subsequently observed the concurrent induction of endoplasmic reticulum (ER) stress, as evidenced by a dilated ER ultrastructure and the upregulation of the expression of UPR markers (ATF6, p-PERK, p-IRE1α, and CHOP), as well as neuroinflammation, characterized by microglial activation and elevated expression of proinflammatory mediators (IL-6, IL-1β, and ICAM-1). These molecular pathologies were associated with decreased neuronal activity and the characteristic cognitive-affective deficits associated with POD. Critically, both pharmacological inhibition of TRPV4 (HC067047) and hippocampal CA3-specific Trpv4 knockdown reversed these pathologies and rescued the behaviour. Inhibiting NMDAR with MK801 recapitulated these therapeutic benefits. Furthermore, TRPV4 was significantly upregulated in early-onset Alzheimer's disease patients. Our study defines a novel TRPV4-GluN1 axis that drives POD pathogenesis, suggesting that it is a promising therapeutic target.},
}

@article {pmid41792330,
year = {2026},
author = {Song, Z and Hu, H and Zhang, W and Zheng, X and Liang, L and Zhao, B and Song, G and Li, J and Li, S and Wen, Y and Zhang, B and Wang, W and Deng, G and Zhang, C and Jiang, H and Hu, S and Tu, H and Wu, M and Li, H},
title = {The glycolytic metabolite phosphoenolpyruvate restricts cGAS-driven inflammation to promote healthy aging.},
journal = {Nature aging},
volume = {},
number = {},
pages = {},
pmid = {41792330},
issn = {2662-8465},
support = {32341003//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Aging involves multiple detrimental changes in the systemic milieu, leading to functional deterioration and age-related diseases. However, the potential self-protective adaptive alterations during aging remain underexplored. Here we show that phosphoenolpyruvate (PEP), a glycolytic metabolite, acts as a protective factor against age-related chronic inflammation. Longitudinal analyses in mice and humans reveal a biphasic PEP trajectory, characterized by initial accumulation followed by progressive decline. Blocking PEP accumulation exacerbates inflammation and accelerates aging phenotypes, whereas PEP administration before its decline promotes healthy aging in mice. In aged humans, high PEP levels strongly correlate with lower inflammation and healthier traits. Mechanistically, PEP acts as an endogenous inhibitor of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway by competitively binding to cGAS. Moreover, PEP alleviates neuroinflammation and improves cognitive function in an Alzheimer's disease mouse model. Thus, our findings define PEP accumulation as an evolutionarily conserved geroprotective mechanism, positioning PEP as a promising intervention for aging and associated diseases.},
}

@article {pmid41792234,
year = {2026},
author = {Yu, H and Wang, F and Yuan, JQ and Chen, J and Zhang, KY and Jia, D and Gong, J and Mao, Y and Bi, S and Zhang, YQ and Lan, ZC and Yu, HY and Chai, GS},
title = {HMGCS2-dependent β-OHB/H3K9bhb ameliorates synaptic plasticity and cognition in Alzheimer's disease.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {41792234},
issn = {2092-6413},
support = {82401671//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82505712//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81601121//National Natural Science Foundation of China (National Science Foundation of China)/ ; BK20211238//Natural Science Foundation of Jiangsu Province (Jiangsu Provincial Natural Science Foundation)/ ; },
abstract = {Ketogenic diet (KD) can significantly ameliorate cognition in Alzheimer's disease (AD), but the specific mechanism is not clear. Histone3-lysine9-β-hydroxybutyrylation (H3k9bhb), a novel histone modification mark induced by ketogenesis-generated β-hydroxybutyrate (β-OHB), may be involved in the prevention and treatment of AD. Here we report that β-OHB and H3K9bhb were reduced in the hippocampus of triple transgenic AD male mice (3xTg-AD) mice. Reduced H3K9bhb levels were also observed in patients with AD. The 3xTg-AD mice exhibited a low enrichment of H3K9bhb on the promoters of NMDA receptor subunits and Syn1 and axon-related genes together with impaired synaptic plasticity, all of which were rescued by 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2, a rate-limiting enzyme of β-OHB synthesis) upregulation. Moreover, β-OHB replenishment enhanced H3K9bhb in 3xTg-AD mice, leading to an increase of NMDA receptor subunits and Syn1 and cognitive function in an HMGCS2-dependent manner. Thus, HMGCS2 is a key molecular switch of cognitive impairment, and targeting HMGCS2 or β-OHB replenishment appropriately may serve as a novel therapeutic strategy for AD treatment.},
}

@article {pmid41792133,
year = {2026},
author = {Xu, Q and Li, G and Zhang, H and Jiang, Z and Gao, X and Li, Z and Langhi Prata, LGP and Kirkland, JL and Zhang, G and Sun, Y},
title = {The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-70302-9},
pmid = {41792133},
issn = {2041-1723},
support = {82130045, 82350710221 and 82571777//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {Aging is a primary risk factor for chronic diseases, with cellular senescence as an effective target to delay, prevent or alleviate age-related disorders. Here we report in vitro screening outputs from a natural medicinal agent library, wherein dihydromyricetin, a natural flavonoid, showed senotherapeutic potential. Dihydromyricetin protects senescent fibroblasts against further DNA damage and attenuates the senescence-associated secretory phenotype, acting as a senomorphic agent. Proteomics suggests that dihydromyricetin promotes nuclear translocation of peroxiredoxin 2 (PRDX2) to facilitate DNA repair in senescent cells. In prematurely aged mice, dihydromyricetin administration mitigates tissue aging and age-related physiological decline. In anticancer regimens, dihydromyricetin improves outcomes of chemotherapy. However, dihydromyricetin demonstrates senolytic activity against senescent microglial cells, whose basal PRDX2 expression remains low, by impairing mitochondrial function to promote apoptosis. In mice developing Alzheimer's disease, dihydromyricetin eliminates senescent microglial cells from amyloid β-protein plaques and alleviates neurodegenerative symptoms. Together, our study proposes dihydromyricetin as a natural senotherapeutic agent for mitigating age-related morbidities, including but not limited to cancers and Alzheimer's disease.},
}

@article {pmid41792131,
year = {2026},
author = {Cao, Y and Willis, BA and Horie, K and Wildsmith, KR and Koyama, A and Sachdev, P and Penner, N and Charil, A and Irizarry, M and Reyderman, L},
title = {Neuro-Dynamic Quantitative Systems Pharmacology (QSP) model describing Alzheimer's disease pathophysiology and treatment effects.},
journal = {NPJ systems biology and applications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41540-026-00677-4},
pmid = {41792131},
issn = {2056-7189},
abstract = {Lecanemab, an anti-amyloid antibody, has demonstrated a significant clinical benefit in slowing cognitive decline in early Alzheimer's disease (AD). A mechanistic Neuro-Dynamic Quantitative Systems Pharmacology (QSP) model was developed to capture the temporal and biological complexity of AD progression. This QSP model incorporates three interlinked modules reflecting core aspects of AD pathology: Aβ accumulation, tau pathology, and cognitive decline, where Aβ accumulation promotes tau pathology, which leads to neuronal damage and cognitive impairment. A large multivariate dataset was assembled from 4056 subjects participating in lecanemab studies and the Alzheimer's Disease Neuroimaging Initiative (ADNI) to inform and validate the model. Virtual populations-based model simulations successfully reproduced the hallmark cascade of AD pathology, consistent with the well-known Jack curve, from amyloid buildup to tau spread and cognitive decline over decades. Simulations accurately predicted all endpoints evaluated from the lecanemab trials and were further validated against data from other anti-Aβ therapies. Importantly, the model revealed that Aβ protofibrils are more potent drivers of tau pathology than plaques. In summary, the Neuro-Dynamic QSP model is the first of its kind to mechanistically link amyloid accumulation, tau pathology, and cognitive decline in AD, providing a powerful framework for simulating clinical scenarios and understanding disease mechanisms.},
}

@article {pmid41791567,
year = {2026},
author = {Guo, P and Zhao, J and Wang, C and Bai, Y and Zhang, B and Liu, A},
title = {Effect of DL0410 and tetrahydrocurcumin (LG0367) alone and in combination on learning and memory in vascular dementia.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178730},
doi = {10.1016/j.ejphar.2026.178730},
pmid = {41791567},
issn = {1879-0712},
abstract = {Vascular dementia (VaD) is one of the most common neurodegenerative diseases, and there is no effective therapy to prevent or cure VaD to date. 1,1'-(1,1'-Biphenyl-4,4'-diyl)bis(3-piperidino-1-propanone) dihydrochloride (DL0410) is a novel multi-target small-molecule drug against Alzheimer's disease (AD), with particularly outstanding acetylcholinesterase (AChE) inhibitory activity and Histamine H3 receptor (H3R) inhibitory activity. Natural derivative 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (LG0367) is a metabolite of curcumin. Previous studies have demonstrated that LG0367 exhibited better pharmacokinetic properties and therefore displayed better pharmacological activity than curcumin. Here, using bilateral common carotid artery occlusion (2VO) rat model, we found that the combined treatment of DL0410 and LG0367 had a much better effect on improving cognitive function in rats than single-drug treatment or donepezil, suggesting a synergistic effect between the small-molecule drug DL0410 and the natural derivertive LG0367. In addition, we found that the combined DL0410 and LG0367 treatment had significant synergic effects on inhibiting AChE production in cortex of 2VO rats. Furthermore, compound-target network and enrichment analyses revealed that DL0410 and LG0367 exhibit synergistic potential against VaD based on multiple mechanisms. In addition, the study also showed that the combination treatment had remarkable synergic effects on decreasing inflammatory responses and oxidative stress, protecting mitochondrial structure, reducing the release of astrocytes, and decreasing neuronal damage and activating the expression of SHH protein in the cortex and hippocampus of 2VO rats. Our findings not only demonstrated a potent synergistic effect between the synthetic small-molecule DL0410 and the natural derivative LG0367, but also illuminate a promising "symptom-to-root" therapeutic strategy for VaD, providing a systematic and evidence-based model for modernizing phytotherapy. Ultimately, this study will provide important information for future clinical trials aimed at translating this synergistic combination into a tangible "multi-target, multi-mechanism" treatment option for VaD patients.},
}

@article {pmid41791565,
year = {2026},
author = {Cui, J and Huang, R and Dong, X},
title = {Efficacy and mechanisms of Icariin in the treatment of Alzheimer's disease: a systematic review and Meta-analysis of a preclinical study.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178706},
doi = {10.1016/j.ejphar.2026.178706},
pmid = {41791565},
issn = {1879-0712},
abstract = {Alzheimer's disease (AD) is a neurodegenerative condition that predominantly affects elderly individuals, characterised by progressive cognitive dysfunction, memory impairment and behavioural changes. Icariin (ICA), the primary active ingredient of the traditional Chinese medicine Epimedium spp., has demonstrated significant potential in the treatment of neurological disorders. Nevertheless, the precise mechanisms through which it exerts its anti-AD effects remain to be elucidated. And this meta-analysis aimed to discuss the mechanisms by which ICA exerts its anti-AD effects and the differences in the efficacy of different doses of ICA by evaluating behavioral indicators and biochemical characteristics. A total of 31 pre-clinical studies were included, and the results showed that ICA treatment significantly improved cognitive dysfunction in animal models of AD in terms of resistance to neurotoxic substances, inhibition of oxidative stress, anti-inflammation, inhibition of apoptosis, modulation of neuronal autophagy, and protection of nerves to promote regeneration. Furthermore, 68 mg/kg of ICA was identified as the most effective doses in terms of improving cognition. However, further research is required, incorporating studies of higher quality and larger sample sizes, in addition to clinical trials, in order to verify the efficacy and safety of this approach in neurological disorders.},
}

@article {pmid41791447,
year = {2026},
author = {Pettis, JA and Orshoski, M and Pal, S and Allen, AM and Ortega Zepeda, M and Wysocki, VH and Kuret, J},
title = {Efficient tag-less purification of recombinant human tau proteins.},
journal = {Analytical biochemistry},
volume = {},
number = {},
pages = {116095},
doi = {10.1016/j.ab.2026.116095},
pmid = {41791447},
issn = {1096-0309},
abstract = {Tau proteins normally function as part of the neuronal cytoskeleton but aggregate to form filamentous inclusions in tauopathies such as Alzheimer's disease. The diverse functions of tau protein are frequently interrogated using biochemical assays that require highly purified tau as substrate. Conventional recombinant tau purification leverages polyhistidine (His6) tags to enable rapid and efficient isolation through immobilized metal affinity chromatography (IMAC). Preparation of native tau by this approach requires removal of His6 tags through additional processing steps. Here we report a protocol for purifying native recombinant full-length tau protein that retains the speed, convenience, broad availability and scalability of IMAC while eliminating the need for post-purification proteolytic cleavage. The method has been validated across a wide array of tau constructs, including full-length isoforms, missense mutants, and a truncation construct containing an aggregation-prone region of the microtubule-binding domain. Owing to its scalability and reproducibility, the method is well suited for structure-activity relationship investigations involving curated tau variant libraries.},
}

@article {pmid41791248,
year = {2026},
author = {Yuki, A and Nishita, Y and Nakamura, A and Kato, T and Tange, C and Zhang, S and Ando, F and Shimokata, H and Otsuka, R},
title = {Ten-year longitudinal effects of physical activity and apolipoprotein E ..4 genotype on precuneus atrophy in Japanese older adults.},
journal = {Archives of gerontology and geriatrics},
volume = {145},
number = {},
pages = {106194},
doi = {10.1016/j.archger.2026.106194},
pmid = {41791248},
issn = {1872-6976},
abstract = {BACKGROUND: The apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for Alzheimer's disease, is associated with early atrophy in the precuneus and posterior cingulate cortex. Whether physical activity can mitigate this atrophy in high-risk APOE ε4 carriers remains unclear. This study aimed to determine whether physical activity can reduce such neurodegenerative changes in older adults carrying this allele.

METHODS: This 10-year longitudinal study included 295 community-dwelling older adults (154 men and 141 women; age ≥65 years). Baseline physical activity was measured using accelerometers and analyzed according to activity intensity. Participants were categorized as APOE ε4 carriers or non-carriers. Volumes of the precuneus and posterior cingulate cortex were assessed using longitudinal magnetic resonance imaging. Sex-stratified linear mixed models examined the interaction between physical activity and APOE ε4 status on brain volume changes, adjusting for relevant covariates.

RESULTS: The moderate-to-vigorous physical activity (MVPA) × APOE ε4 × year effect in women's left precuneus was significant unadjusted but not after false discovery rate (FDR; 16 models) and exploratory. Left precuneus volume declined significantly over 10 years regardless of MVPA level or APOE ε4 genotype (each p < 0.0001). However, among APOE ε4 carriers, greater time spent in MVPA slowed the rate of volume decline. No similar effect was observed in men.

CONCLUSIONS: Higher habitual MVPA may be associated with slower left precuneus decline in APOE ε4-positive women. As this exploratory three‑way effect was FDR‑nonsignificant, targeted replication is needed to clarify the role of everyday activity in genetically vulnerable groups.},
}

@article {pmid41791120,
year = {2026},
author = {Peng, Y and Yao, SY and Wu, SL and Yang, H and Zhang, X and Kazuo, S and Liu, J and Du, MQ and Lin, LX and Kang, XH and Jiang, DY},
title = {New Perspective: Bench to Bedside Evidence of the Role of CD8+ T Cells in Alzheimer's Disease.},
journal = {Immunity, inflammation and disease},
volume = {14},
number = {3},
pages = {e70380},
doi = {10.1002/iid3.70380},
pmid = {41791120},
issn = {2050-4527},
support = {C202303076574//Scientific Research Project of the Hunan Provincial Health Commission, People's Republic of China/ ; 2023039//Key Plans of Hunan Administration Traditional Chinese Medicine, PR China/ ; 2022XYLH19//University-Hospital Joint Fund of Hunan University of Chinese Medicine, PR China/ ; 2021B-003//Fund for Creative Research Groups at the Affiliated First Hospital of Hunan Traditional Chinese Medical College, PR China/ ; 2021-009//Technology Plan Project of Zhuzhou City, Hunan Province, PR China/ ; //Fund for Research Chief of Clinical Department of Affiliated First Hospital of Hunan Traditional Chinese Medical College, PR China/ ; },
abstract = {INTRODUCTION: Amyloid beta plaques and tau tangles are the primary hallmarks of Alzheimer's disease (AD). Recently, passive anti-Aβ immunotherapy for AD has markedly advanced, as supported by evidence from AD animal models and clinical trials. Whereas innate immunity significantly contributes to AD pathology, it does not fully represent the immune mechanisms linked to this condition. Therefore, focus should be directed toward adaptive immunity, encompassing both humoral and cellular immunity.

METHODS: Relevant publications and clinical trial data up to February 2026 were systematically reviewed to summarize the mechanisms, therapeutic targets, safety profiles, and translational applications of CD8+ T cells in AD.

RESULTS: Clinical and animal studies have particularly suggested a potential involvement of T cells in AD pathogenesis. T cells that infiltrate the central nervous system (CNS) exert both protective and detrimental effects on neural tissue in AD. Because autoreactive CD8+ T cells are generally expected to have cytotoxic effects on CNS cells, they have received less attention. Nevertheless, accumulating evidence suggests that CD8+ Treg cells are involved in various diseases.

CONCLUSION: However, the function of anti-Aβ-specific CD8+ T cells in Alzheimer's disease (AD) remains ambiguous. Many subsets of CD8+ T cells have been well-studied in autoimmunity. We suggest that CD8+ T cell subsets identified in AD studies may constitute a promising area for future AD research.},
}