@article {pmid42032706,
year = {2026},
author = {Wanner, IB and Halford, J and Lopez, J and Shen, S and Chen, Y and Zhao, H and Salas, C and Loo, RO and Robicsek, S and Ellingson, BM and Gornbein, J and Van Meter, TE and Shaw, G and Loo, JA and Vespa, PM},
title = {GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {},
pmid = {42032706},
issn = {2051-5960},
support = {"First in man" award # 20182601: "Clinical study and trauma culture model experiments"//Dana Foundation/ ; Clinical Neuroscience "First in man" award # 20182601: "Clinical study and trauma culture model experiments"//Dana Foundation/ ; "Clinical study and trauma culture model experiments"//Brain Injury Research Center (BIRC), State of California/ ; "Clinical study and trauma culture model experiments"//Brain Injury Research Center (BIRC), State of California/ ; # 1R43NS106972-01 "Validation and GFAP proteoform characterization for assay use"//National Institute of Health (NIH), Institute of Neuronal Disorders and Stroke (NINDS), Small Business Innovation Research, SBIR/ ; # 1R43NS106972-01 "Validation and GFAP proteoform characterization for assay use"//National Institute of Health (NIH), Institute of Neuronal Disorders and Stroke (NINDS), Small Business Innovation Research, SBIR/ ; Sponsored Research Agreement: "GFAP fragment analyses"//Abbott Diagnostics/ ; Sponsored Research Agreement: "GFAP fragment analyses"//Abbott Diagnostics/ ; Sponsored Research Agreement: "Validation studies and patent licensing"//BRAINBox Solutions Inc., Richmond VA, USA/ ; R01 NS052831 "Biochemical markers of severe traumatic brain injury"//National Institute of Health (NIH), Institute of Neuronal Disorders and Stroke (NINDS)/ ; },
abstract = {UNLABELLED: Glial fibrillary acidic protein (GFAP) is a significant clinical biomarker of traumatic brain injury (TBI), yet understanding the nature, timing, and impact of its degraded and modified products would inform clinical utility. We report novel GFAP breakdown products (BDPs) and post-translational modifications (PTMs) that are unique to TBI including fragment- and patient-specific citrullination signatures that destabilize GFAP filaments. GFAP and its fragments were sequenced by mass spectrometry (MS) from severe TBI patients’ cerebrospinal fluid (CSF) and sera, identifying two distinct TBI-specific jointly generated product sets within the rod-domain covering coil1 (20–26 kDa) and coil2 (15–19 kDa). Their endings differed from GFAP fragments described in Alzheimer’s and Alexander disease. Label-free quantification showed biofluid co-product abundance differences with coil1-BDPs enriched over coil2-BDPs. Coil imbalance was independently confirmed by immunoblot densitometry in twenty-three TBI patients. Measurements over ten days showed injury day peaks of full-length and end-clipped GFAP fragments, while proteolytic 37/39 kDa and small fragments remained elevated. Six-month outcome (Extended Glasgow Outcome Scale) correlated with GFAP fragments, whereas levels of uncleaved and end-clipped GFAP did not. A human astrocyte culture trauma model provided mechanistic insights linking fluid GFAP levels, subcellular localization, and injury-induced astrocytopathy. A new cleavage site between the two coils was identified through selective epitope loss. Coil1-BDPs were fluid-released post-injury, while coil2-BDPs remained intracellular. Their cellular retention was explained by non-filamentous aggregation of citrulline-modified coil2-BDP’s in pathological astrocytes. Trauma-triggered proteolysis involved calpains and caspases in specific astrocyte injury states using protease inhibitors and live-dye-reporter imaging. These novel data link TBI biofluid GFAP fragments with assembly-defective GFAP aggregation in pathological astrocytes. Clinical TBI outcome correlated with GFAP degradation rather than with overall GFAP release. These translational findings indicate that TBI biomarker GFAP undergoes degradation and modification alongside astrocyte pathology, providing a new conceptual framework for investigating biomarker-associated astrocyte proteinopathy potentially linked to post-traumatic neurodegeneration.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-026-02240-y.},
}

@article {pmid42032766,
year = {2026},
author = {Chen, B and Gao, P and Liu, H and Xu, D and Wang, Q and Yang, M and Tan, H and Xiao, Z and Tian, S and Wang, Z and Zheng, Y and Zheng, X and Liang, S and Liu, Q and Li, J and Zhong, X and Ning, Y},
title = {Olfactory radiomics signatures link pTau217 to cognitive impairment in probable Alzheimer's disease: a multi-cohort machine learning study.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02053-0},
pmid = {42032766},
issn = {1758-9193},
support = {2023B0303010003//Guangdong Province Key Areas Research and Development Programs-Brain Science and Brain-Inspired Intelligence Technology/ ; No. 82371428, No. 82171533//National Natural Science Foundation of China/ ; 2022A1515011623；2024A1515011035//Natural Science Foundation of Guangdong Province, China/ ; No.202201003//The Science and Technology Program of Guangzhou Liwan District/ ; 2021ZD0201800//Brain Science and Brain-Like Intelligence Technology/ ; 2025-2027//Guangzhou Municipal Key Discipline in Medicine/ ; },
}

@article {pmid42032832,
year = {2026},
author = {Yang, H and Wang, Y and Wang, Y and Cheng, H and Huang, Y and Xu, Y and Zhang, C and Wang, C},
title = {Synthesis and Evaluation of a PET Radiotracer [[18]F]LY3000328 Selectively Targeting the Cysteine Protease Cathepsin S.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00167},
pmid = {42032832},
issn = {1948-7193},
abstract = {Cathepsin S (Cat S) is a cysteine protease broadly expressed in the brain and a key mediator of neuroinflammatory processes, making it an attractive target for molecular imaging agents and drug development. Here, we report the development and evaluation of [[18]F]LY3000328, a positron emission tomography (PET) radiotracer that selectively targets Cat S and is derived directly from the clinical Cat S inhibitor LY3000328. [[18]F]LY3000328 was synthesized via a ruthenium-assisted late-stage [18]F-deoxyfluorination of the corresponding phenol precursor. In vitro autoradiography, the marked reduction in tracer uptake under blocking conditions suggests specific binding of [[18]F]LY3000328 to Cat S, and the significantly higher uptake in transgenic 5xFAD mouse brain sections indicates upregulation of Cat S in Alzheimer's disease (AD), consistent with previously reported findings. However, in vivo PET imaging in wild-type mice revealed low blood-brain barrier (BBB) penetration and no significant reduction under blocking conditions, suggesting that limited BBB permeability may constrain its efficiency as a brain PET tracer. Despite its limited brain penetration, these results suggest that [[18]F]LY3000328 may serve as a useful starting scaffold for further optimization of physicochemical and pharmacokinetic properties toward Cat S-targeted PET imaging of neuroinflammation in AD and potentially other neurodegenerative disorders.},
}

@article {pmid42033004,
year = {2025},
author = {Gu, M and Ren, K and Zhang, Z and Chen, X},
title = {[Role of succinylation modification in central nervous system diseases].},
journal = {Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences},
volume = {50},
number = {12},
pages = {2449-2457},
pmid = {42033004},
issn = {1672-7347},
mesh = {Humans ; *Protein Processing, Post-Translational ; *Central Nervous System Diseases/metabolism ; *Succinic Acid/metabolism ; Sirtuins/metabolism ; Alzheimer Disease/metabolism ; Stroke/metabolism ; Subarachnoid Hemorrhage/metabolism ; Lysine/metabolism ; Animals ; Acyl Coenzyme A ; },
abstract = {Succinylation is a post-translational modification that occurs on lysine residues and is mediated by succinyl-CoA, an intermediate of the tricarboxylic acid (TCA) cycle. It can significantly affect protein conformation, activity, stability, and interactions with other molecules, thereby participating in the regulation of important biological processes such as cellular metabolism, energy homeostasis, and signaling pathways. In recent years, increasing evidence has shown that succinylation plays a key role in central nervous system (CNS) diseases, particularly in Alzheimer's disease, stroke, subarachnoid hemorrhage (SAH), and microglial glioma. Succinylation modification participates in neuronal injury and repair processes by influencing mitochondrial function, oxidative stress, autophagic flux, immune responses, and inflammation. A systematic description of the enzymatic and non-enzymatic regulatory mechanisms of succinylation, along with a summary of its functional roles and potential therapeutic value in different CNS diseases, especially the role of desuccinylases such as sirtuin 5 (SIRT5) as potential therapeutic targets, can provide a new theoretical basis and conceptual support for understanding the pathogenesis of CNS diseases and developing targeted intervention strategies. Future research should further clarify the core characteristics of disease-specific succinylation profiles and the integration patterns of multi-omics data, elucidate the molecular mechanisms of crosstalk among post-translational modifications, and promote the clinical translation of biomarkers and precision therapeutic drugs based on succinylation pathways.},
}

Humans
*Protein Processing, Post-Translational
*Central Nervous System Diseases/metabolism
*Succinic Acid/metabolism
Sirtuins/metabolism
Alzheimer Disease/metabolism
Stroke/metabolism
Subarachnoid Hemorrhage/metabolism
Lysine/metabolism
Animals
Acyl Coenzyme A

@article {pmid42033046,
year = {2026},
author = {Pace, T and Levenstein, JM and Quigley, BL and Houston, R and Bouças, AP and Andrews, SC},
title = {The Myokine Irisin Represents an Indirect Pathway Linking Exercise to Hippocampal Subfields Relevant to Alzheimer's Disease and Neurogenesis.},
journal = {Aging cell},
volume = {25},
number = {5},
pages = {e70497},
pmid = {42033046},
issn = {1474-9726},
support = {//Wilson Foundation/ ; },
mesh = {Humans ; *Alzheimer Disease/metabolism/pathology ; Aged ; *Fibronectins/metabolism/blood ; Male ; Female ; *Hippocampus/metabolism/pathology ; *Neurogenesis ; *Exercise/physiology ; Cross-Sectional Studies ; Middle Aged ; Magnetic Resonance Imaging ; Myokines ; },
abstract = {While exercise is shown to reduce hippocampal atrophy, the underlying molecular mechanisms remain to be fully elucidated. Animal studies suggest the myokine irisin underlies exercise-related hippocampal benefits, though human evidence is lacking. We cross-sectionally examined 74 healthy older adults (age 65.47 ± 8.56 years). Participants completed Godin Leisure-Time exercise questionnaires, provided fasting blood for irisin measurement and underwent structural MRI with hippocampal subfield segmentation. Hierarchical regression and mediation analyses tested irisin-mediated exercise-hippocampus relationships, controlling for age, sex and education. Exercise positively associated with circulating irisin (β = 0.365, p = 0.003). Irisin positively associated with bilateral hippocampal volumes (right: β = 0.353, p = 0.001; left: β = 0.275, p = 0.012), strongest in right-CA3 (β = 0.530), right-CA4/dentate gyrus (β = 0.471), and bilateral CA1 (β = 0.336-0.373) subfields. Mediation analysis revealed all exercise-hippocampus relationships operated indirectly through irisin. This study provides first human evidence that irisin is a molecular mechanism linking exercise to hippocampal volume, particularly in subfields critical for memory, neurogenesis and Alzheimer's pathology. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12620000054910.},
}

Humans
*Alzheimer Disease/metabolism/pathology
Aged
*Fibronectins/metabolism/blood
Male
Female
*Hippocampus/metabolism/pathology
*Neurogenesis
*Exercise/physiology
Cross-Sectional Studies
Middle Aged
Magnetic Resonance Imaging
Myokines

@article {pmid42033067,
year = {2026},
author = {Todarwal, Y and Linares, M and Norman, P},
title = {Molecular Dynamics Study of the Binding of Cationic, Anionic, and Neutral Luminescent Conjugated Ligands to the Alzheimer Folds of Aβ(1-42) and Tau Fibrils.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {27},
number = {8},
pages = {e202500902},
pmid = {42033067},
issn = {1439-7633},
support = {2023-5171//Swedish Research Council/ ; },
mesh = {*Amyloid beta-Peptides/chemistry/metabolism ; *tau Proteins/chemistry/metabolism ; Ligands ; *Molecular Dynamics Simulation ; Humans ; *Peptide Fragments/chemistry/metabolism ; Anions/chemistry/metabolism ; *Alzheimer Disease/metabolism ; Cations/chemistry/metabolism ; Binding Sites ; Protein Binding ; *Amyloid/chemistry/metabolism ; Protein Folding ; },
abstract = {Unbiased atomistic molecular dynamics simulations have been employed to examine the binding interactions between amyloid fibrils (Aβ(1-42) and tau) with various ligands: anionic pFTAA, qFTAA-CN, neutral HS-276, and cationic bTVBT4. The ligand-fibril interactions were analyzed in a two-step approach. First, an analysis of the spatial distributions of the ligands around the amyloid fibril protofilaments was carried out to identify prospective binding sites. Second, the associated ligand-fibril binding energies at these sites were determined using umbrella sampling. The results reveal that pFTAA and qFTAA-CN share common binding sites in both Aβ(1-42) and tau fibrils. Ligands bTVBT4 and HS-276, on the other hand, are found to have different binding sites in Aβ(1-42) but share the same site in tau fibrils. An analysis of the spatial distributions of all ligand-fibril pair combinations under comparable conditions shows the lowest densities when bTVBT4 interacts with Aβ(1-42) and HS-276 with the tau fibril. These findings are corroborated by fluorescence costaining experiments, in which bTVBT4 and HS-276 show no correlation with Aβ-specific and tau-specific antibody markers, respectively. Further structural analysis reveals significant changes in the conformations of all ligands upon binding to the proteins compared to their conformations in aqueous solution. The binding of the anionic ligands (multiple localized negative charges) to fibrils is primarily driven by Coulombic forces, whereas the binding of the neutral HS-276 and cationic bTVBT4 (single delocalized positive charge) is governed by Lennard-Jones interactions. This highlights the influence of charges on binding, providing insights for the design of future ligands targeting Aβ(1-42) and tau fibrils.},
}

*Amyloid beta-Peptides/chemistry/metabolism
*tau Proteins/chemistry/metabolism
Ligands
*Molecular Dynamics Simulation
Humans
*Peptide Fragments/chemistry/metabolism
Anions/chemistry/metabolism
*Alzheimer Disease/metabolism
Cations/chemistry/metabolism
Binding Sites
Protein Binding
*Amyloid/chemistry/metabolism
Protein Folding

@article {pmid42033091,
year = {2026},
author = {Merritt, VC and Valocchi, E and Lopez, FV and Asimakopoulos, G and Clark, AL and Kodama, L and Jak, AJ and Liu, L and Chanfreau-Coffinier, C},
title = {Differential associations between traumatic brain injury severity and four dementia phenotypes in military veterans.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71370},
pmid = {42033091},
issn = {1552-5279},
support = {HT9425-23-1-0230//Department of Defense USAMRAA/ ; },
mesh = {Humans ; *Veterans/statistics & numerical data ; *Brain Injuries, Traumatic/complications/epidemiology ; Male ; *Dementia/epidemiology/etiology ; Female ; Phenotype ; Aged ; Middle Aged ; United States/epidemiology ; Severity of Illness Index ; Electronic Health Records ; United States Department of Veterans Affairs ; },
abstract = {INTRODUCTION: National Veterans Affairs electronic health records were used to examine the association between traumatic brain injury (TBI) severity and four dementia phenotypes ranging from narrow (strict AD) to broad (all-cause dementia).

METHODS: Veterans with TBI (n = 91,753) and a propensity score-matched comparison group of veterans without TBI (n = 183,506) were included. Four validated dementia phenotypes defined using International Classification of Diseases (ICD) codes were evaluated. The association between TBI severity and each dementia phenotype was examined using adjusted logistic regression.

RESULTS: TBI severity was significantly associated with increased odds of developing dementia across the three broader dementia phenotypes in a dose-response manner (moderate/severe/penetrating TBI > mild TBI). Those with unclassified TBI had disease risk falling in between mild and more severe TBI. In contrast, TBI was associated with decreased risk of strict AD across all severity levels.

DISCUSSION: Findings support a dose-response relationship between TBI severity and broader dementia risk but raise questions regarding the TBI-AD link.},
}

Humans
*Veterans/statistics & numerical data
*Brain Injuries, Traumatic/complications/epidemiology
Male
*Dementia/epidemiology/etiology
Female
Phenotype
Aged
Middle Aged
United States/epidemiology
Severity of Illness Index
Electronic Health Records
United States Department of Veterans Affairs

@article {pmid42033099,
year = {2026},
author = {Luo, QH and Li, F and Yang, L and Pan, HQ and Zhu, WP and Hu, P and Tao, CM and Yin, M and Zhang, S and Liao, QY and Chen, ZH and Shu, HX and Zhu, XY and Yan, TF and Liu, X and Tu, JL and Zhu, XG},
title = {Endothelial NAD[+] depletion drives vascular senescence and neuroinflammation via mtDNA-cGAS/STING-CD38 signaling in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71423},
pmid = {42033099},
issn = {1552-5279},
support = {82501463//National Natural Science Foundation of China/ ; 82260278//National Natural Science Foundation of China/ ; 20232BAB216047//Jiangxi Provincial Natural Science Foundation/ ; 20242BAB25478//Jiangxi Provincial Natural Science Foundation/ ; 20242BAB26136//Jiangxi Provincial Natural Science Foundation/ ; 20242BAB20383//Jiangxi Provincial Natural Science Foundation/ ; 2023M741521//China Postdoctoral Science Foundation/ ; },
mesh = {Animals ; *NAD/deficiency/metabolism ; *Alzheimer Disease/metabolism/pathology ; Mice ; *DNA, Mitochondrial/metabolism ; Signal Transduction ; *Endothelial Cells/metabolism ; *Nucleotidyltransferases/metabolism ; Membrane Proteins/metabolism ; *Neuroinflammatory Diseases/metabolism ; Mice, Transgenic ; Cellular Senescence ; Humans ; Disease Models, Animal ; Mitochondria/metabolism ; STING Protein ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; Niacinamide/analogs & derivatives ; Pyridinium Compounds ; },
abstract = {BACKGROUND: Endothelial dysfunction has emerged as early and pivotal event in Alzheimer's disease (AD), yet the molecular mechanisms linking vascular aging to neuroinflammation remain elusive.

METHODS: We used APP/PS1 mice and amyloid beta (Aβ)-challenged brain endothelial cells (BECs) to understand the mechanisms of nicotinamide adenine dinucleotide (NAD[+]) deficiency, and its relationship with endothelial senescence and neuroinflammation in AD pathology. Nicotinamide riboside supplementation was administered to APP/PS1 mice to determine whether restoration of NAD[+] homeostasis mitigates AD-related vascular and inflammatory pathology.

RESULTS: NAD[+] deficiency induced voltage-dependent anion channel 1 (VDAC1) oligomerization, mitochondrial DNA (mtDNA) leakage, and cGAS/STING-IRF3 activation, promoting endothelial senescence and SASP production with NAD[+]-consuming enzyme CD38 upregulation. Senescent BECs triggered IL-6-dependent microglial activation. NR treatment restored mitochondrial integrity, suppressed cGAS-STING signaling, and reduced neuroinflammation, improving vascular function and cognition.

DISCUSSION: Aβ-driven NAD[+] deficiency initiates a VDAC1-mtDNA-cGAS/STING cascade that promotes endothelial senescence and neurovascular inflammation in AD pathology, and amplifies neuroinflammation through BEC-microglia crosstalk, highlighting NAD[+] restoration as a promising AD therapeutic strategy.},
}

Animals
*NAD/deficiency/metabolism
*Alzheimer Disease/metabolism/pathology
Mice
*DNA, Mitochondrial/metabolism
Signal Transduction
*Endothelial Cells/metabolism
*Nucleotidyltransferases/metabolism
Membrane Proteins/metabolism
*Neuroinflammatory Diseases/metabolism
Mice, Transgenic
Cellular Senescence
Humans
Disease Models, Animal
Mitochondria/metabolism
STING Protein
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
Niacinamide/analogs & derivatives
Pyridinium Compounds

@article {pmid42033138,
year = {2026},
author = {You, P and Zhu, P and Yu, H and Wang, L and Su, B},
title = {Presenilin 1 is located in the mitochondrial inner inner membrane and regulates mitochondrial cristae junction protein arrangement and cristae formation in HEK293 cells.},
journal = {Acta biochimica et biophysica Sinica},
volume = {},
number = {},
pages = {},
doi = {10.3724/abbs.2026064},
pmid = {42033138},
issn = {1745-7270},
abstract = {Presenilin 1 (PS1), a key pathogenic factor in familial Alzheimer's disease, is implicated in the regulation of mitochondrial functions, yet its precise sub-mitochondrial localization and underlying mechanisms remain poorly understood. In this study, we generate PS1-knockout cell lines to investigate the role of PS1 in mitochondrial structure and function. Our results indicate that PS1 is directly localized in the mitochondrial inner membrane. PS1 deficiency leads to reduced ATP production, impaired mitochondrial respiration capacity, decreased mitochondrial membrane potential, disrupted Ca [2+] homeostasis, and elevated ROS accumulation. Moreover, loss of PS1 leads to abnormal mitochondrial cristae structure. Further analysis reveals that PS1 interacts with mitochondrial inner membrane proteins. Its absence promotes ATAD3A oligomerization and disrupts its arrangement at mitochondrial cristae junctions, leading to expansion of the mitochondria-associated membrane and instability of mitochondrial DNA. Our findings demonstrate that PS1 acts as a central regulator of mitochondrial cristae morphogenesis by modulating protein interaction networks at cristae junctions, thereby illuminating fundamental molecular mechanisms contributing to mitochondrial dysfunction in Alzheimer's disease.},
}

@article {pmid42033405,
year = {2026},
author = {Cuperfain, AB and Pishdadian, S and Binns, MA and Black, SE and Chertkow, H and Freedman, M and Louis, J and Ma, C and Masellis, M and Mclaughlin, PM and Ramirez, J and Tang-Wai, DF and Tartaglia, MC and Kumar, S and , },
title = {Examining the effects of alcohol use on verbal memory processes in older adults with mild cognitive impairment.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261444995},
doi = {10.1177/13872877261444995},
pmid = {42033405},
issn = {1875-8908},
abstract = {BackgroundExcessive alcohol use is associated with memory impairment due to its effects on encoding and retrieval of information. However, the underlying mechanisms in those with neurodegenerative disorders is not well understood.ObjectiveWe evaluated the effects of alcohol on verbal memory processes in those with mild cognitive impairment (MCI).MethodsData came from two cohorts, the Comprehensive Assessment of Neurodegeneration and Dementia and the Ontario Neurodegenerative Disease Research Initiative. Participants were diagnosed with MCI due to Alzheimer's disease or cerebrovascular disease, and categorized into "zero", "low-medium", or "high" alcohol use groups. We compared occurrence of any intrusion, total intrusions, change in intrusions post-interference, and intrusion subtypes on the Rey Auditory Verbal Learning Test across groups.ResultsWe analyzed 521 participants with high (n = 79), low-medium (n = 304), and zero (n = 138) alcohol use. Mean (SD) age was 71.6 (7.4) years and did not differ between groups. The high alcohol use group had higher occurrence of any intrusions (96.2%) compared to the low-medium (87.2%), and zero (92.8%) alcohol use groups (p = 0.027). Alcohol use was associated with increased post-interference intrusions, with the high group adjusted mean (M), standard error (SE) = 1.7 (0.3), low-medium group M(SE) = 1.0 (0.2), and zero group M(SE) = 0.9 (0.2), (p = 0.027). Other intrusion subtypes did not differ between groups.ConclusionsIndividuals with MCI and excessive alcohol use are more susceptible to interference from recently learned task-irrelevant information. Findings may inform future research regarding mechanisms of alcohol related memory impairment.},
}

@article {pmid42033406,
year = {2026},
author = {Fujiwara, Y and Toyoda, K and Maruyama, S and Kitano, M and Toda, H and Kanazawa, T},
title = {Dementia screening with the Rivermead Behavioural Memory Test: A machine learning analysis.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443699},
doi = {10.1177/13872877261443699},
pmid = {42033406},
issn = {1875-8908},
abstract = {BackgroundWith the advent of anti-amyloid-β monoclonal antibody therapies and the growing societal burden of dementia, early identification of Alzheimer's disease and related dementias has become a clinical priority.ObjectiveTo evaluate the diagnostic accuracy of a machine learning model using a neuropsychological battery to classify individuals as Healthy controls, mild cognitive impairment (MCI), or Dementia, and to identify neuropsychological tests and cognitive domains that contributed most to classification accuracy, determining optimal tests for dementia screening.MethodsIn this retrospective cross-sectional single-center study, we analyzed 590 participants evaluated for suspected dementia. The final sample comprised 74 Healthy controls, 190 individuals with MCI, and 326 with Dementia (including 269 with Alzheimer's disease). Scores from the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Japanese version (MoCA-J), Rivermead Behavioural Memory Test (RBMT), Japanese Adult Reading Test (JART), and Wechsler Adult Intelligence Scale-III were input into a random forest machine learning model. Model performance was assessed using the area under the ROC curve (AUC). A variable importance analysis determined each test's relative contribution to classification.ResultsThe multiclass model achieved an AUC of 0.898. RBMT was the strongest contributor, exceeding MMSE and MoCA-J. In borderline MMSE/MoCA-J subsets, adding RBMT improved classification performance for both Healthy versus MCI and MCI versus Dementia decisions.ConclusionsRBMT provides substantial incremental value for dementia-related diagnostic discrimination, particularly as a second-line assessment when brief screening results are borderline. However, its administration time may limit its role as a universal first-line screening tool.},
}

@article {pmid42033408,
year = {2026},
author = {Dhana, K and Aggarwal, NT and Arfanakis, K and Sacks, FM and Barnes, LL},
title = {Dietary intervention and cognition across Alzheimer's disease biomarker levels: The MIND clinical trial.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261442856},
doi = {10.1177/13872877261442856},
pmid = {42033408},
issn = {1875-8908},
abstract = {BackgroundThe cognitive response to dietary interventions may differ according to levels of Alzheimer's disease-related plasma biomarkers.ObjectiveUsing data from the MIND clinical trial, we examined whether baseline biomarkers, including Aβ40, the Aβ42/40 ratio, and p-tau181, modified the association between the MIND diet and longitudinal change in global cognition.MethodsThe MIND randomized clinical trial enrolled 604 community-dwelling adults aged 65-84 years without cognitive impairment at baseline. Recruitment occurred from January 2017 to April 2018, with data collection continuing through June 2021. Participants were randomized in a 1:1 ratio to the MIND or control diet for 3 years, with counseling on diet adherence and weight loss support provided at the same frequency throughout the intervention. Annual change from baseline in a global cognitive composite z-score was derived from a 12-test battery, with higher scores indicating better cognitive performance.ResultsOf the 602 individuals included in the analysis, 391 (65%) were female, and the mean baseline age was 70.4 (SD = 4.2) years. Baseline levels of Aβ40 and p-tau181 modified the association between MIND assignment and longitudinal change in global cognition, with significant between-group differences in biomarker-related annual cognitive slopes for Aβ40 (β=0.027, 95%CI 0.006-0.048) and p-tau181 (β=0.023, 95%CI 0.002-0.043), but not for the Aβ42/40 ratio.ConclusionsThe association between the MIND diet intervention and cognition varied by baseline levels of Aβ40 and p-tau181, with greater improvement in cognitive scores in the MIND group than in the control group among individuals with higher biomarker levels.Trial Registration: ClinicalTrials.gov Identifier: NCT02817074.},
}

@article {pmid42033409,
year = {2026},
author = {Bahl, A and Honig, LS and Kang, MS and Sanchez, D and Reyes-Dumeyer, D and Manly, JJ and Lantigua, RA and Brickman, AM and Vardarajan, BN and Mayeux, R and Gu, Y},
title = {Plasma phosphorylated tau 181, vascular risk factors, and cognition in elderly Hispanics.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261443653},
doi = {10.1177/13872877261443653},
pmid = {42033409},
issn = {1875-8908},
abstract = {BackgroundCerebrovascular risk factors, a group of conditions that reduce or disrupt blood flow to the brain, often occur with Alzheimer's disease (AD) and may contribute to the pathogenesis and cognitive decline. Hispanic individuals are at increased risk of vascular risk factors compared to non-Hispanic white counterparts.ObjectiveWe examined associations among vascular risk factors, including hypertension, diabetes, history of heart disease, and history of stroke, with plasma phosphorylated tau-181 (P-tau181) and cognition.MethodsWe pooled data from 2159 two cohorts of older Hispanic adults. Vascular risk factors were self-reported. Plasma P-tau181 was measured using standardized protocols. Linear regression and mediation models assessed associations among vascular risk, P-tau181, and global cognition, stratified by cognitive status.ResultsOverall, P-tau181 was significantly associated with vascular risk factors and inversely associated with cognitive function. However, vascular risk factors were not independently associated with cognition. Among cognitively unimpaired individuals, vascular risk factors mediated the association between P-tau181 and cognition, while in cognitively impaired individuals, P-tau181 was strongly and independently associated with cognition, without mediation by vascular risk factors.ConclusionsAmong elderly without dementia, vascular risk factors mediate the association between P-tau181 and cognition. However, among individuals with dementia there is no mediation, suggesting that the association between P-tau181 with dementia is independent of cerebrovascular pathology.},
}

@article {pmid42033410,
year = {2026},
author = {Gu, X and Terebuh, P and Xu, R and Kaelber, DC and Davis, PB},
title = {Age-related macular degeneration and dementia: Association through pathogenesis or visual impairment?.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261438849},
doi = {10.1177/13872877261438849},
pmid = {42033410},
issn = {1875-8908},
abstract = {BackgroundStudies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship between AMD and dementia.ObjectiveTo evaluate the association between AMD and 5-year dementia risk in non-blind patients.MethodsThis retrospective cohort study used TriNetX to compare non-blind patients with exudative AMD (n = 35,021) and non-exudative AMD (n = 96,809) to those without AMD (n = 1,801,879) for five-year dementia risk. Blind (n = 90,615) and non-blind (n = 800,737) patients were compared. Cohorts were propensity-matched for confounding factors.ResultsNon-blind AMD patients had decreased Alzheimer's disease risk, while blindness showed a strong positive association. Exudative AMD had HR of 0.84 (95% CI = [0.72, 0.97]), non-exudative AMD had HR of 0.95 (95% CI = [0.87, 1.04]), but blindness increased Alzheimer's disease risk (95% HR = 1.29, CI = [1.17, 1.41]).ConclusionsThese findings suggest that previously reported associations between AMD and dementia may be partially mediated by visual impairment. The modest reduction in dementia risk in non-blind AMD patients may reflect differences in healthcare utilization or treatment exposure among AMD patients.},
}

@article {pmid42033565,
year = {2026},
author = {Ishii, K},
title = {Brain PET in the era of anti-amyloid-β antibody therapy for Alzheimer disease.},
journal = {Japanese journal of radiology},
volume = {},
number = {},
pages = {},
pmid = {42033565},
issn = {1867-108X},
abstract = {Here the current and emerging roles of brain positron emission tomography (PET) in Alzheimer's disease (AD) in the era of anti-amyloid-β antibody therapy, with a focus on clinical applications, methodological considerations, and future perspectives were reviewed. A narrative review of the literature on PET imaging in AD, including FDG-PET, amyloid PET, and tau PET, was conducted with particular emphasis on their clinical utility in diagnosis, and disease monitoring. Relevant guidelines, including appropriate use criteria and Japanese clinical guidelines, were also reviewed. FDG-PET provides valuable information for the differential diagnosis of neurodegenerative dementias based on characteristic hypometabolic patterns, although its role remains supportive due to the lack of direct assessment of molecular pathology. Amyloid PET enables noninvasive visualization of cerebral amyloid-β deposition and has become essential for confirming eligibility for anti-amyloid therapies. Standardized use criteria and interpretation guidelines are critical for appropriate clinical implementation. Quantitative approaches, such as standardized uptake value ratios (SUVRs) and the Centiloid scale, improve comparability across studies and institutions. Tau PET reflects neurofibrillary pathology and correlates with disease severity and progression, with increasing relevance for patient stratification. In addition, recent advances in high-resolution dedicated brain PET systems and artificial intelligence-based image analysis are expected to enhance diagnostic performance and workflow efficiency. In the era of disease-modifying therapy, brain PET imaging has become integral to the clinical management of AD. Amyloid PET is indispensable for treatment eligibility, while tau PET provides complementary information on disease stage and prognosis. Ongoing technological and methodological advancements will further expand the role of PET imaging in precision medicine for dementia.},
}

@article {pmid42033726,
year = {2026},
author = {Wang, Y and Pandey, S and Weber, M and Choy, MK and Wu, T and Chernov-Rogan, T and Adrian, M and Tsai, MC and Ngu, H and Foreman, O and Xie, L and Hanson, JE},
title = {Complement C3aR deletion does not attenuate degeneration in a tauopathy model or alter acute inflammation-induced gene expression changes.},
journal = {Cell reports},
volume = {45},
number = {5},
pages = {117313},
doi = {10.1016/j.celrep.2026.117313},
pmid = {42033726},
issn = {2211-1247},
abstract = {Aberrant activation of the classical complement pathway in the brain is implicated in contributing to synapse loss and neurodegeneration in various neurodegenerative conditions. Given that C3aR is a druggable target in the complement pathway, we evaluated the potential of C3aR knockout (KO) to rescue neurodegeneration in a tauopathy model and neuroinflammatory responses in an acute endotoxemia model. We found that C3aR KO did not rescue Tau pathology, microglia activation markers, neurodegeneration, or behavioral abnormalities in tauopathy model mice. While we found that endotoxemia resulted in numerous transcriptional changes, including distinct alterations in subpopulations of microglia, astrocytes, and oligodendrocytes, C3aR KO did not impact these alterations. Together, our results suggest that the beneficial effects of blocking the complement classical pathway in neurodegeneration models are likely independent of C3aR activation and raise questions about the rationale for therapeutically targeting C3aR for neurodegenerative disease.},
}

@article {pmid42033766,
year = {2026},
author = {Miguel, ACC and Martins-Teixeira, L and Godoy, C and Lima, GMA and Lima-Costa, MF and Barbosa, MG and Ferri, CP},
title = {Inequities in Dementia Diagnosis: Evidence From the ELSI-Brazil Study.},
journal = {International journal of geriatric psychiatry},
volume = {41},
number = {4},
pages = {e70219},
doi = {10.1002/gps.70219},
pmid = {42033766},
issn = {1099-1166},
support = {404965/2012-1//Brazilian Ministry of Health/ ; TED 28/2017//Brazilian Ministry of Health/ ; TED 4/2022//Brazilian Ministry of Health/ ; 20836//COPID/DECIV/SAPS/ ; 22566//COPID/DECIV/SAPS/ ; 23700//COPID/DECIV/SAPS/ ; 25560//COPID/DECIV/SAPS/ ; 25552//COPID/DECIV/SAPS/ ; 27510//COPID/DECIV/SAPS/ ; TED 32/2022//COPID/DECIV/SAPS/ ; },
mesh = {Humans ; Brazil/epidemiology ; Male ; Female ; Aged ; Cross-Sectional Studies ; *Dementia/diagnosis/epidemiology ; Middle Aged ; Aged, 80 and over ; Longitudinal Studies ; Socioeconomic Factors ; Logistic Models ; Educational Status ; },
abstract = {OBJECTIVE: To estimate the national proportion of undiagnosed dementia cases in Brazil, examine its distribution across Brazilian regions sociodemographic subgroups, and identify factors associated with receiving a diagnosis.

METHODS: We conducted a cross-sectional, population-based analysis using baseline data (2015-2016) from the Brazilian Longitudinal Study of Aging (ELSI-Brazil), a nationally representative survey of community-dwelling adults. Dementia was identified through an established algorithm incorporating cognitive testing and functional impairment, combined with self-reported medical diagnosis of Alzheimer's disease. Underdiagnosis was defined as meeting dementia criteria without a prior medical diagnosis. Sociodemographic, clinical, cognitive, and functional variables were assessed. Survey-weighted logistic regression models estimated factors associated with underdiagnosis.

RESULTS: Among 5249 participants aged ≥ 60 years, 392 met criteria for dementia. Overall, 83.1% (95% CI: 76.5-88.1) had no previous diagnosis. Underdiagnosis was more frequent in poorer regions (90.2%) than in richer regions (76.0%), and higher among illiterate individuals (93.9%). In fully adjusted models, older age (OR = 0.91; 95% CI: 0.85-0.97), more years of education (OR = 0.86; 95% CI: 0.76-0.96), a higher number of chronic conditions (OR = 0.72; 95% CI: 0.54-0.97), and better memory performance (OR = 0.68; 95% CI: 0.56-0.84) were associated with a lower likelihood of underdiagnosis, while living alone was associated with a higher likelihood of underdiagnosis (OR = 3.65 [1.05-12.6]).

CONCLUSIONS: About four in five older Brazilians meeting dementia criteria had no prior clinical diagnosis, with marked sociodemographic and regional disparities. Both individual factors-such as age, education, and multimorbidity-and structural inequities across regions influenced diagnostic likelihood. Strengthening early-detection strategies, improved health professional training, and regionally tailored approaches may improve recognition of dementia in Brazil's public health system.},
}

Humans
Brazil/epidemiology
Male
Female
Aged
Cross-Sectional Studies
*Dementia/diagnosis/epidemiology
Middle Aged
Aged, 80 and over
Longitudinal Studies
Socioeconomic Factors
Logistic Models
Educational Status

@article {pmid42033804,
year = {2026},
author = {Abdel-Sater, KA},
title = {Cold Climate and Alzheimer's Disease: A Narrative Review of Biomedical and Environmental Mechanisms.},
journal = {Acta neurologica Taiwanica},
volume = {35},
number = {2},
pages = {70-78},
doi = {10.4103/ant.ANT-D-25-00060},
pmid = {42033804},
issn = {1028-768X},
mesh = {Humans ; *Alzheimer Disease/epidemiology/etiology ; *Cold Temperature/adverse effects ; Oxidative Stress ; *Climate ; },
abstract = {Emerging evidence suggests that exposure to cold environments may influence Alzheimer's disease (AD) pathogenesis through interconnected vascular, inflammatory, metabolic, and thermoregulatory mechanisms. Aging impairs physiological resilience to cold stress, which may exacerbate neurodegenerative processes in vulnerable individuals. This narrative review summarizes findings from epidemiological, mechanistic, and interventional studies on the relationship between cold exposure and AD. This article is a narrative review informed by a structured literature search conducted in PubMed and Scopus databases up to July 2025. Boolean operators such as ("cold exposure" OR "cold climate") AND ("Alzheimer's disease" OR "neurodegeneration") were applied. While not a systematic review, a PRISMA-style flowchart was solely for transparency, illustrating how the literature was screened. No meta-analytic methods or formal bias assessment tools were applied. Cold exposure is associated with cerebral vasoconstriction, glucose hypometabolism, sleep disruption, mitochondrial stress, and increased permeability of the blood-brain barrier. These changes promote neuroinflammation and oxidative stress, which are key contributors to the pathology of AD. Reduced brown adipose tissue with aging makes people more sensitive to cold. Apolipoprotein E (APOE) ε4 allele carriers seem to be more susceptible to these stresses. Epidemiological data support a higher dementia risk in colder climates, with seasonal and regional variations persisting after adjustment for confounders. Exposure to cold environments may act as a modifiable risk factor for AD, particularly in aging populations with impaired thermoregulation. While evidence points to plausible mechanistic links, further longitudinal and experimental studies are required. Integrating environmental variables into neurodegenerative risk models may enhance prevention strategies and support personalized interventions.},
}

Humans
*Alzheimer Disease/epidemiology/etiology
*Cold Temperature/adverse effects
Oxidative Stress
*Climate

@article {pmid42033865,
year = {2026},
author = {Wang, F},
title = {Polyphenols and physical activity stimulate gut microbiota mediated Nrf2 signaling to combat neurodegeneration.},
journal = {Pathology, research and practice},
volume = {283},
number = {},
pages = {156478},
doi = {10.1016/j.prp.2026.156478},
pmid = {42033865},
issn = {1618-0631},
abstract = {Polyphenols and regular physical activity are increasingly recognized as complementary lifestyle interventions that influence the gut-brain axis and contribute to neuroprotection. Emerging evidence highlights the central role of the gut microbiota in mediating these effects by transforming dietary and host-derived substrates into bioactive metabolites. These metabolites can activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, a key regulator of cellular antioxidant defenses, mitochondrial function, and anti-inflammatory responses processes that are critically impaired in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review synthesizes current mechanistic insights into how polyphenol-derived metabolites and exercise-induced alterations in gut microbial composition converge to modulate Nrf2 signaling. We discuss the roles of key microbiota-derived metabolites, including short-chain fatty acids, urolithins, and indole derivatives, in regulating oxidative stress, neuroinflammation, and synaptic function. Furthermore, we examine evidence from preclinical models supporting the synergistic effects of dietary polyphenols and physical activity on gut microbiota-mediated neuroprotection. Finally, we address translational challenges and highlight the potential of integrating dietary and exercise-based strategies to harness microbiota-dependent Nrf2 activation. This integrative framework provides a basis for developing personalized, microbiome-informed interventions aimed at delaying or mitigating neurodegeneration.},
}

@article {pmid42033978,
year = {2026},
author = {Shir, D and Seifar, F and Ertekin-Taner, N},
title = {Multi-ancestry studies in multi-omics of Alzheimer's disease: Recent insights and future directions.},
journal = {Current opinion in neurobiology},
volume = {99},
number = {},
pages = {103205},
doi = {10.1016/j.conb.2026.103205},
pmid = {42033978},
issn = {1873-6882},
abstract = {The past decade of multi-omics studies revealed perturbations in genetic, epigenetic, transcriptomic, proteomic, and metabolic networks in Alzheimer's disease (AD) detected in brain, cerebrospinal fluid (CSF), and blood biospecimens. Interactions among these networks and environmental factors are thought to contribute to risk and progression of this neurodegenerative dementia. Understanding the molecular and environmental risk in AD across all populations is essential in the development of cures and biomarkers for this complex disease. While most molecular studies to date have focused on populations of European ancestry, emerging multi-ancestry and multi-omics studies are revealing both shared and ancestry-specific biological signatures associated with disease susceptibility, biomarker profiles, and clinical presentation. Genomic studies show that established AD risk loci such as APOE, ABCA7, and TREM2 exhibit ancestry-dependent effects, while trans-ethnic genome-wide association studies identified novel disease risk loci (e.g., LRRC4C, LHX5-AS1) and protective haplotypes unique to African American (AA) and admixed populations. Epigenomic and transcriptomic studies reveal ancestry-linked variation in chromatin accessibility, DNA methylation, and gene expression, particularly in immune, lipid metabolism, and synaptic pathways. Proteomic analyses demonstrate differences in CSF and brain protein networks, including extracellular matrix and synaptic modules enriched or reduced in AA AD brains. Metabolomic and lipidomic data further highlight differential abundance in non-European cohorts. Integrating these multi-omics layers across ancestries provides a framework for understanding how genetic background and environmental context interact to drive AD heterogeneity. Such integrative, ancestry-aware approaches will refine biomarker interpretation, improve diagnostic accuracy, and guide development of therapeutics for AD.},
}

@article {pmid42033997,
year = {2026},
author = {Ersözlü, E and Meyer, F and Preis, L and Arslan, O and Gref, D and Droste, L and Hellmann-Regen, J and , },
title = {An exploratory analysis of plasma biomarkers associated with cerebral amyloid angiopathy.},
journal = {Neurobiology of aging},
volume = {165},
number = {},
pages = {1-7},
doi = {10.1016/j.neurobiolaging.2026.04.004},
pmid = {42033997},
issn = {1558-1497},
abstract = {Cerebral amyloid angiopathy (CAA) remains diagnostically challenging, particularly in asymptomatic individuals. While CAA often co-exists with Alzheimer's disease (AD), it may even have a direct impact on AD pathophysiology and the cognitive decline within the clinical course of AD. While fluid biomarkers are well established for AD pathology, reliable markers to characterize CAA are lacking. We analyzed two subsets of participants from the Alzheimer's Disease Neuroimaging Initiative with available plasma biomarker measurements from a 145-analyte multiplex immunoassay panel: one with T2*-weighted gradient-echo magnetic resonance imaging (MRI) data (n = 21) and another with postmortem neuropathological data (n = 24). We defined CAA as ≥ 2 lobar microbleeds on MRI or moderate-to-severe neocortical amyloid angiopathy on neuropathological examination. Plasma analytes were assessed twice per participant, one year apart, with the earlier sample obtained up to 6.6 years prior to either the first MRI or neuropathological examinations. In both cohorts, various markers related to inflammation, lipid metabolism, and cell adhesion were associated with CAA proxy measures. Specifically, both increased (Fas ligand receptor, Receptor for Advanced Glycosylation End-Products, Osteopontin, and Vascular Cell Adhesion Molecule-1) and decreased (Vitronectin, Endothelial Growth Factor) biomarker levels were associated with lobar microbleeds, while increased apolipoproteins (ApoAII, ApoCI, ApoCIII, ApoE, and clusterin) and decreased AXL were associated with CAA severity in neuropathology. Ratios between inversely associated markers enhanced correlation strength and differed between CAA and non-CAA. Given the small sample sizes in our exploratory analyses, larger studies are required to evaluate the discriminatory potential and clinical translatability of the identified biomarkers for CAA.},
}

@article {pmid42033998,
year = {2026},
author = {Yang, B and Earnest, T and Bilgel, M and Albert, MS and Johnson, SC and Davatzikos, C and Erus, G and Masters, CL and Resnick, SM and Miller, MI and Bakker, A and Morris, JC and Benzinger, TLS and Gordon, BA and Sotiras, A and , and , },
title = {Predicting future cognitive impairment in preclinical Alzheimer's disease using amyloid PET and MRI: A multisite machine learning study.},
journal = {Neurobiology of aging},
volume = {165},
number = {},
pages = {8-23},
doi = {10.1016/j.neurobiolaging.2026.04.005},
pmid = {42033998},
issn = {1558-1497},
abstract = {Predicting the likelihood of developing Alzheimer's disease (AD) dementia in at-risk individuals is important for the design of and optimal recruitment for clinical trials of disease-modifying therapies. Machine learning (ML) has been shown to excel in this task; however, there remains a lack of models developed specifically for the preclinical AD population, who display early signs of abnormal brain amyloidosis but remain cognitively unimpaired. Here, we trained and evaluated ML classifiers to predict whether individuals with preclinical AD will progress to mild cognitive impairment or dementia within multiple fixed time windows, ranging from one to five years. Models were trained on regional imaging features extracted from amyloid positron emission tomography and magnetic resonance imaging pooled across seven independent sites and from two amyloid radiotracers ([[18]F]-florbetapir and [[11]C]-Pittsburgh-compound-B). Out-of-sample generalizability was evaluated via a leave-one-site-out and leave-one-tracer-out cross-validation. Classifiers achieved an out-of-sample receiver operating characteristic area-under-the-curve of 0.66 or greater when applied to all except one hold-out sites and 0.72 or greater when applied to each hold-out radiotracer. Additionally, when applying our models in a retroactive cohort enrichment analysis on A4 clinical trial data, we observed increased statistical power of detecting differences in amyloid accumulation between placebo and treatment arms after enrichment by ML stratifications. As emerging investigations of new disease-modifying therapies for AD increasingly focus on asymptomatic, preclinical populations, our findings underscore the potential applicability of ML-based patient stratification for recruiting more homogeneous cohorts and improving statistical power for detecting treatment effects for future clinical trials.},
}

@article {pmid42034047,
year = {2026},
author = {Jaroszynski, C and Amer, M and Beauchamp, A and Lerch, JP and Sotiropoulos, SN and Mars, RB},
title = {Translating brain anatomy and disease from mouse to human in latent gene expression space.},
journal = {EBioMedicine},
volume = {127},
number = {},
pages = {106259},
doi = {10.1016/j.ebiom.2026.106259},
pmid = {42034047},
issn = {2352-3964},
abstract = {BACKGROUND: The mouse model is the most widely used animal model in neuroscience, yet translating findings to humans suffers from the lack of formal models comparing the mouse and the human brain. Here, we devised a framework using mouse and human gene expression to build a quantitative common space and apply it to models of neurodegenerative disease.

METHODS: We trained a variational autoencoder on mouse spatial transcriptomics, and embedded mouse and human gene orthologs in the model's latent space. We computed a latent cross-species similarity matrix for translation and compared translated maps to human ground truth evidence.

FINDINGS: We established the validity of our model based on anatomical homology. Independent of species, brain areas with similar latent patterns clustered together, improving the homology of known anatomical pairs, and preserving principles of brain organisation. Importantly, translating brain alterations in mouse disease models predicted human patterns of brain changes in Alzheimer's and Parkinson's diseases. We further determined the best mouse model for the AD patients, based on how well the translations matched the patient data, across multiple models and timepoints.

INTERPRETATION: Our work provides i) a quantitative bridge across evolutionary divergence between the human and the predominant preclinical species, ii) a predictive framework to help design and evaluate disease models. By highlighting which models are best suited across stages of disease, we effectively support the understanding of disease mechanisms, assist in the workflow of clinical trials, and ultimately accelerate the transformation of findings into improved human outcomes.

FUNDING: Supported by the Biotechnology and Biological Sciences Research Council (BBSRC) UK, the Medical Research Council (MRC) UK, the European Research Council, and the NIHR Oxford Health Biomedical Research Centre.},
}

@article {pmid42034060,
year = {2026},
author = {Tosoni, G and Ayyildiz, D and Snoeck, S and Moreno-Jiménez, EP and Penning, A and Santiago-Mujika, E and Ruiz Ormaechea, O and Lee, H and Poovathingal, S and Davie, K and Bryois, J and Macnair, W and Anink, J and De Vries, LE and Farmand, S and Nutma, E and Swaab, DF and Aronica, E and Middeldorp, J and Thuret, S and Roybon, L and Basak, O and Fitzsimons, CP and Lucassen, PJ and Salta, E},
title = {Transcriptional profiles of immature neurons in aged human hippocampus track Alzheimer's pathology and cognitive resilience.},
journal = {Cell stem cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.stem.2026.04.002},
pmid = {42034060},
issn = {1875-9777},
abstract = {The existence and functional significance of immature neurons in the adult human brain, particularly in the context of neurodegenerative disorders, remain an open question. Although rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus both under healthy conditions and in Alzheimer's disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing in aged healthy, AD, and dementia-resilient human hippocampus samples to probe immature neuronal signatures and gene expression alterations associated with AD pathology and resilience. By applying an integrated experimental and computational pipeline, we identified persistent populations of immature neurons across all donor groups, with transcriptional profiles reflecting "juvenile" cellular functions, which are compromised in AD. Our findings suggest that the presence of these immature neuronal populations per se may actively contribute to maintaining homeostasis within the aged human hippocampus and to cognitive resilience in AD.},
}

@article {pmid42034066,
year = {2026},
author = {Fu, J and Sköldunger, A and Bradshaw, A and Broulíková, HM and Brück, CC and Chapel, JM and Grimm, S and Hansson, A and Herring, WL and Hlávka, J and Hoang, MT and Jönsson, L and Landeiro, F and Mar, J and McKean, A and Misik, M and Neumann, P and Rapp, T and Ritchie, C and Schiel, A and Sun, Y and Trépel, D and Trueman, D and van der Veere, PJ and van Rosmalen, L and Vonsy, JL and Walker, L and Wimo, A and Winblad, B and Xia, X and Handels, R},
title = {Health-economic challenges for new Alzheimer's disease treatments.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {6},
pages = {100575},
doi = {10.1016/j.tjpad.2026.100575},
pmid = {42034066},
issn = {2426-0266},
}

@article {pmid42034128,
year = {2026},
author = {Bao, YW and Zhou, Y and Wei, DF and Ji, YQ and Shen, DM and Liu, YY and Guo, LL},
title = {Longitudinal Alterations in Morphometric Inverse Divergence Networks Among Diabetes Patients with Progressive Cognitive Decline.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111898},
doi = {10.1016/j.brainresbull.2026.111898},
pmid = {42034128},
issn = {1873-2747},
abstract = {BACKGROUND: Diabetes mellitus (DM) is associated with an elevated risk of cognitive decline, though trajectories are heterogeneous. This study investigated whether a novel, clinically applicable measure of brain network integrity, the Morphometric Inverse Divergence (MIND) network, could differentiate and predict cognitive progression in DM.

METHODS: We retrospectively analyzed 101 DM participants (41 cognitively normal, 60 with mild cognitive impairment) from the Alzheimer's Disease Neuroimaging Initiative, classifying them into stable (DM_S, n=64) or decline (DM_D, n=37) group based on longitudinal diagnostic conversion. MIND networks were constructed from multiple cortical morphological features derived from T1-weighted MRI and graph theory measurements were further analyzed. Using network-based statistics (NBS) and its extension NBS-predict, we tested whether subject-level connectomes were associated with long-term DM-related cognitive worsening.

RESULTS: At baseline, DM_D individuals exhibited significantly lower cognitive scores and a focal subnetwork of disrupted morphometric similarity, primarily involving temporal regions. Longitudinally, DM_D individuals showed a more targeted pattern of network change that significantly altered global efficiency, local efficiency, and path length exclusively, while stable individuals, the brain underwent more widespread changes. Crucially, baseline MIND networks significantly predicted long-term cognitive progression status (accuracy = 63.1%, p = 0.034). The predictive subnetwork was rich in transmodal connections involving the temporoparietal, default mode, and limbic networks.

CONCLUSION: These findings indicate that cognitive decline in DM is preceded by specific disruptions in the brain's structural connectome. The MIND method shows promise as a network-based biomarker for identifying at-risk individuals and predicting cognitive trajectory, potentially driving advanced network analyses toward real-world applicability.},
}

@article {pmid42034585,
year = {2026},
author = {Soares, MD and Carvalho, V and de Sousa, DA and Araújo, R},
title = {Prodromal neurology: Is this the end of semiology?.},
journal = {Journal of the neurological sciences},
volume = {486},
number = {},
pages = {125939},
doi = {10.1016/j.jns.2026.125939},
pmid = {42034585},
issn = {1878-5883},
}

@article {pmid42034728,
year = {2026},
author = {Sheng, J and Zhong, H and Zhang, Q and Zhang, R and Gong, Z and Lin, J and Chen, Z},
title = {Adaptive neighborhood aggregation graph neural network for early diagnosis of Alzheimer's disease.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-50351-2},
pmid = {42034728},
issn = {2045-2322},
support = {LZ24F010007//Natural Science Foundation of Zhejiang Province/ ; 62271177//National Natural Science Foundation of China/ ; },
abstract = {Early diagnosis of Alzheimer's disease (AD) is crucial for timely intervention but remains challenging due to subtle and heterogeneous brain alterations, particularly in the mild cognitive impairment (MCI) stage. To address this issue, we propose a pathology-aware Adaptive Neighborhood Aggregation Graph Neural Network (ANA-GNN) to model the brain as a dynamic and task-driven graph for multimodal AD classification. The framework integrates three synergistic components: an adaptive neighborhood aggregation module that aligns each node's receptive field with disease-specific heterogeneity, an importance-weighted pooling mechanism that enhances discriminative graph-level representations by prioritizing biologically relevant regions, and a gated multimodal fusion strategy that adaptively balances imaging and non-imaging information. Evaluated on an expanded cohort of 707 subjects from the ADNI dataset, ANA-GNN achieved an overall accuracy of 85.23% and an F1-score of 85.44%, consistently outperforming state-of-the-art baselines such as BrainGNN and Graph Transformers. Furthermore, the identified high-importance brain regions, including the hippocampus, amygdala, and posterior cingulate cortex, align with known AD biomarkers, demonstrating the model's biological interpretability and potential as a reliable tool for early AD diagnosis.},
}

@article {pmid42034769,
year = {2026},
author = {Matias, I and Prociów, P and Daza, EJ and Kliegel, M and Wac, K},
title = {Passive digital health technologies for Alzheimer's disease screening and diagnosis: a systematic review.},
journal = {NPJ digital medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41746-026-02650-1},
pmid = {42034769},
issn = {2398-6352},
support = {Research LIVES - Overcoming vulnerability: Life course perspectives (51NF40-185901)//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; Research LIVES - Overcoming vulnerability: Life course perspectives (51NF40-185901)//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 101156751//EU SHIELD/ ; },
abstract = {Passive digital health technologies (DHTs) are increasingly promoted as scalable tools for detecting Alzheimer's disease and related dementias (ADRD) earlier than routine clinic visits. We searched six major databases for English-language studies published between January 2014 and July 2024 that used passively collected, real-world DHT data for ADRD screening or diagnosis. Thirty studies met the criteria. Population sizes were highly skewed (median = 87; range 12-82,829), and most designs were longitudinal (53%) and fully passive (68%). Wrist-worn accelerometers and photoplethysmography sensors dominated, though several studies also used gait, sleep, voice, radar, or posture-tracking devices. A cross-study synthesis showed that those two modalities were primarily applied to memory, attention, and language tasks. Nineteen studies reported median accuracy, sensitivity, specificity, and precision between 80-90%, with F1-score and AUC medians approaching 78%, though relying on in-sample cross-validation rather than external cohorts. Reference standards varied widely, data-quality criteria were seldom reported, and fewer than 5% shared datasets publicly. Classification was the predominant modeling strategy, with regression emerging only in recent years. Overall, passive DHTs show promise as low-burden triage tools for population-level ADRD screening, but routine deployment will require more diverse cohorts, harmonized reporting, multimodal privacy-preserving analytics, and rigorous human-factors evaluation.},
}

@article {pmid42034805,
year = {2026},
author = {Monteiro, R and Dunn, JT and Rodriguez, G and Fisher, DW and Dong, H},
title = {Targeting central immune signaling enhances the effects of methylphenidate in alleviating apathy-like behavior in 5xFAD mice.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-49172-0},
pmid = {42034805},
issn = {2045-2322},
support = {R01AG062249-05, 5R01AG079989-03//National Institute of Aging/ ; },
abstract = {Beyond cognitive impairment, Alzheimer's disease (AD) is frequently accompanied by apathy, the most prevalent and burdensome neuropsychiatric symptom (NPS). Apathy significantly impacts AD onset and progression, yet its molecular underpinnings remain unclear. Our previous RNA-sequencing analysis revealed abnormal immune gene expression uniquely associated with apathy in AD patients. In this study, we investigated whether changes in these immune related genes are also linked to apathy-like behavior, and whether administration of C3a receptor antagonist SB290157, alone or with methylphenidate, modifies apathy-like behaviors in 5xFAD mice. We first validated the apathy-related immune hub genes identified in human AD in the prefrontal cortex (PFC) of 16-18 month-old 5xFAD mice using RT-qPCR. Then separate cohorts of similarly aged 5xFAD mice received SB290157 and/or methylphenidate for three weeks. Our results showed that elevated immune hub genes Tyrobp, C3, C3ar, C1qa, C1qb, and C1qc were strongly correlated with apathy-like behavior in 5xFAD mice. Combined SB290157 and methylphenidate treatment improved nest-building behavior, reduced C3 and C3ar expression as well as restored dendritic spine density in the PFC. Our results confirm complement-mediated immune dysregulation is linked to apathy and suggest that co-targeting complement and catecholaminergic pathways may offer a novel therapeutic strategy for alleviating apathy in AD.},
}

@article {pmid42035106,
year = {2026},
author = {Cohen, CE and Fernandez, S and Yaman, U and Ehyaei, AR and Kodosaki, E and Askarova, A and Porter, T and O'Brien, E and , and , and Maruff, P and Nott, A and Hardy, JA and Laws, SM and A Salih, D and Shoai, M},
title = {Genetic drivers of progression in Alzheimer's disease are distinct from disease risk.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02036-1},
pmid = {42035106},
issn = {1758-9193},
support = {President's PhD Scholarships award//Imperial College London/ ; UKDRI-5208//UK Dementia Research Institute through UK DRI Ltd/ ; AISRPG2305\26//Vivensa Foundation/ ; ADSF-24-1345198-C/ALZ/Alzheimer's Association/United States ; GNT1161706, GNT1191535//National Health and Medical Research Council/ ; },
}

@article {pmid42035335,
year = {2026},
author = {Zhang, Q and Chang, C and Jin, C and Shen, L and Long, Q},
title = {Simultaneous Representation Learning of Multi-Omics and Clinical Outcome Data via a Supervised Knowledge-Guided Bayesian Factor Model.},
journal = {Statistics in medicine},
volume = {45},
number = {10-12},
pages = {e70570},
doi = {10.1002/sim.70570},
pmid = {42035335},
issn = {1097-0258},
support = {RF1AG063481/NH/NIH HHS/United States ; R01AG071174/NH/NIH HHS/United States ; },
mesh = {Bayes Theorem ; Humans ; Alzheimer Disease/genetics ; Computer Simulation ; *Genomics/methods ; Models, Statistical ; Multiomics ; },
abstract = {With the advent of high-throughput techniques, multi-omics data and various clinical outcomes have been collected for a range of diseases. Multi-omics data play a crucial role in uncovering complex biological processes, yet simultaneous representation learning of such high-dimensional, heterogeneous multi-modality data along with clinical outcomes remains limited. To address this gap, we propose a supervised knowledge-guided Bayesian factor model for integrative analysis of multi-omics and clinical outcome data. The proposed method simultaneously extracts an informative low-dimensional representation and predicts one or more clinical outcomes of interest. The two-level adaptive shrinkage in the novel hierarchical priors allows for the identification of both active modalities and features, resulting in a biologically meaningful structural identification of the high-dimensional data. Moreover, the method is robust to noisy edges in biological graphs that do not align with ground truth. Finally, the proposed method can handle different data types including both continuous and categorical data. Extensive simulation studies and real data analyses of Alzheimer's disease (AD) data demonstrate the advantages of the proposed approach over existing methods. Notably, our analysis of multi-omics and imaging phenotype data from ADNI provides meaningful insights into the underlying biological mechanisms of AD.},
}

Bayes Theorem
Humans
Alzheimer Disease/genetics
Computer Simulation
*Genomics/methods
Models, Statistical
Multiomics

@article {pmid42035365,
year = {2026},
author = {Chou, PS and Chien, CF and Huang, LC and Yang, YH},
title = {Therapeutic effects of 40 Hz light stimulation on clinical and pathological features of Alzheimer's disease.},
journal = {Dialogues in clinical neuroscience},
volume = {28},
number = {1},
pages = {177-187},
doi = {10.1080/19585969.2026.2658530},
pmid = {42035365},
issn = {1958-5969},
mesh = {Humans ; *Alzheimer Disease/therapy/blood/pathology/psychology ; Male ; Female ; Aged ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; Longitudinal Studies ; Biomarkers/blood ; Aged, 80 and over ; Treatment Outcome ; *Phototherapy/methods ; Middle Aged ; Peptide Fragments/blood ; },
abstract = {BACKGROUND: Current pharmacological treatments offer only limited benefits in altering the course of Alzheimer's disease (AD). Given these limitations, nonpharmacological interventions have emerged as potential therapeutic strategies. This study investigates the therapeutic effects of 40 Hz light stimulation in AD and analyzes blood biomarkers to explore its potential disease-modifying effects.

METHODS: This longitudinal study examined the effects of 40 Hz light stimulation on clinical symptoms and blood biomarkers in AD patients. Fourteen individuals were enrolled, with 11 completing the 3-month light stimulation, and 6 continuing to 6 months for the final blood biomarker analysis, including amyloid beta (Aβ) oligomers, Aβ-40, Aβ-42, tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217), and neurofilament light chain.

RESULTS: At 3 months, cognitive function remained stable or improved in 63.6% of participants, depressive symptoms improved in 54.5%, caregiver burden decreased in 72.7%, and sleep quality improved in 90.9% (p = .014). At 6 months, cognitive function and neuropsychiatric symptoms remained stable or improved in 33.3% and 66.7% of participants, respectively. Biomarker analysis showed decreased Aβ oligomers, increased Aβ-42 and reduced p-tau, suggesting potential disease-modifying effects.

CONCLUSIONS: 40 Hz light stimulation demonstrated short-term benefits in cognitive stability, caregiver burden relief, and sleep improvement, with biomarker findings indicating possible neuroprotective effects.},
}

Humans
*Alzheimer Disease/therapy/blood/pathology/psychology
Male
Female
Aged
Amyloid beta-Peptides/blood
tau Proteins/blood
Longitudinal Studies
Biomarkers/blood
Aged, 80 and over
Treatment Outcome
*Phototherapy/methods
Middle Aged
Peptide Fragments/blood

@article {pmid42035670,
year = {2026},
author = {Dao, S and Cui, C and He, W and Liu, E and Zhang, L and Tang, H},
title = {Design, synthesis and anti-Alzheimer's disease activity evaluation of dual 17β-HSD10 and CDK5/p25 inhibitors based on the naphtho[2,3-b]furan-4,9-dione scaffold.},
journal = {European journal of medicinal chemistry},
volume = {313},
number = {},
pages = {118874},
doi = {10.1016/j.ejmech.2026.118874},
pmid = {42035670},
issn = {1768-3254},
abstract = {A series of novel naphtho[2,3-b]furan-4,9-dione derivatives were designed and synthesized as dual inhibitors targeting 17β-HSD10 and CDK5/p25. Through in vitro enzymatic inhibition assays, blood-brain barrier permeability prediction, and molecular docking analysis, derivative 5l was identified as a lead candidate and selected for further in vivo evaluation. Pharmacodynamic assessment in APP/PS1 transgenic mice demonstrated that 5l significantly improved cognitive performance in the Morris water maze test. Mechanistic studies revealed that 5l not only effectively ameliorated mitochondrial function, but also attenuated aberrant Tau phosphorylation, reduced Aβ deposition, inhibited neuroinflammation, and enhanced neurotrophic support. Western blot results indicated that the neuroprotective effects of 5l were not mediated by modulating the expression levels of 17β-HSD10 and CDK5, but rather through inhibiting their enzymatic activities. Collectively, these findings demonstrate that this class of dual inhibitors counteracts key pathological features of Alzheimer's disease through multi-target and multi-pathway synergy, providing a solid experimental foundation for the development of novel therapeutic agents for AD.},
}

@article {pmid42035704,
year = {2026},
author = {Shahidehpour, RK and Neltner, AM and Klusty, MA and Corbett, C and Gonzalez, AD and Gutman, DA and Fardo, DW and Bachstetter, AD and Bumgardner, C and Flanagan, ME and Nelson, PT},
title = {Data-driven thresholds for standardized classification of severe Alzheimer's disease neuropathology using digital neuropathology.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70102},
doi = {10.1111/bpa.70102},
pmid = {42035704},
issn = {1750-3639},
support = {P30 AG072946/NH/NIH HHS/United States ; T32 AG078110/NH/NIH HHS/United States ; U24 NS133945/NH/NIH HHS/United States ; U24 NS133949/NH/NIH HHS/United States ; R01 AG054459/NH/NIH HHS/United States ; },
abstract = {Alzheimer's disease neuropathological changes (ADNC)-operationalized with semi-quantitative parameters-represent the consensus-based gold standard for diagnostic evaluation of disease severity. Although useful, ADNC diagnostic frameworks have limitations, particularly in advanced disease stages where pathological severity varies widely within a given diagnostic category. Further, some individuals lacking cognitive impairment are inappropriately categorized as having severe ADNC. In this study, quantitative pathology metrics and alternative tissue sampling schemes were integrated with data about premortem cognitive status, in order to derive clinically informed neuropathologic diagnostic thresholds. Specific goals of the current study were to generate data-driven, standardized diagnostic cut-points, with the most severe stages of ADNC having consistent implications: Braak neurofibrillary tangle (NFT) stage V cases being always impaired (MCI or demented) and Braak NFT stage VI cases being always demented. Utilizing whole-slide imaging and AI-based image analysis, object-based (NFT counts) and pixel-based (phosphorylated tau [pTau] burden) quantifications were compared across neocortical regions in three subsamples of cases from the University of Kentucky ADRC autopsy cohort (n = 329, all with clinical evaluations within 2 years of death). We also compared between HALO- and Aperio-based platform results, and between AT8 and PHF-1 pTau antibodies. Applying refined thresholds enabled reclassification of cases previously misaligned with their digitally determined appropriate status: 17% of cases were thus reclassified. The use of commercially available software, standardized classifier architectures, and interoperable analysis pipelines facilitated scalable and reproducible digital quantification. Cross-institutional validation at University of Texas San Antonio, with the same algorithms applied in both research centers, confirmed near-perfect agreement of pathology counts, underscoring shareability and the feasibility of harmonized digital workflows for collaborative research and diagnostic purposes. These findings support the integration of quantitative digital pathology into standard neuropathological protocols and provide a scalable model for future multi-site studies. Enabling comparisons of analytical platforms, pTau antibodies, and anatomical sampling strategies, an updated workflow demonstrated high reproducibility and consistent clinical-pathological correlations.},
}

@article {pmid42035758,
year = {2026},
author = {, },
title = {Burden of 292 causes of death and life expectancy decomposition in Iran, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.},
journal = {The Lancet. Global health},
volume = {14},
number = {5},
pages = {e734-e748},
doi = {10.1016/S2214-109X(26)00031-8},
pmid = {42035758},
issn = {2214-109X},
mesh = {Humans ; Iran/epidemiology ; *Life Expectancy/trends ; *Global Burden of Disease/trends ; Cause of Death/trends ; COVID-19/mortality/epidemiology ; Female ; Male ; Middle Aged ; Adult ; Aged ; Infant ; Adolescent ; Risk Factors ; Child ; },
abstract = {BACKGROUND: Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations.

METHODS: In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates.

FINDINGS: The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286·2 deaths (95% uncertainty interval 267·9-310·5) per 100 000 in 2020 and 250·0 deaths (233·2-272·5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78·0 years (77·7-78·1) in 2019 to 74·3 years (74·0-74·4) in 2020. It steadily recovered to 78·8 years (78·5-79·2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4·19 years, between 2019 and 2020. There was a net gain of 12·4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2·61 years), stroke (1·63 years), neonatal disorders (1·26 years), transport injuries (0·88 years), and neoplasms (0·64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4·0% increase in rate between 2019 and 2023 and led to a net loss of 0·04 years in life expectancy since 1990. Diabetes led to a net loss of 0·09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic.

INTERPRETATION: The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system.

FUNDING: Gates Foundation.},
}

Humans
Iran/epidemiology
*Life Expectancy/trends
*Global Burden of Disease/trends
Cause of Death/trends
COVID-19/mortality/epidemiology
Female
Male
Middle Aged
Adult
Aged
Infant
Adolescent
Risk Factors
Child

@article {pmid42035783,
year = {2026},
author = {Fox, NC and Kohlhaas, S and Schott, JM},
title = {Alzheimer's disease immunotherapy and the amyloid hypothesis: when aggregation obscures interpretation.},
journal = {Lancet (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1016/S0140-6736(26)00789-0},
pmid = {42035783},
issn = {1474-547X},
}

@article {pmid42032309,
year = {2025},
author = {Shebl, N and Salama, M},
title = {Exploring dopa decarboxylase as an ideal biomarker in Parkinson's disease with focus on regulatory mechanisms, cofactor influences, and metabolic implications.},
journal = {npj biomedical innovations},
volume = {2},
number = {1},
pages = {},
pmid = {42032309},
issn = {3005-1444},
abstract = {Parkinson's disease (PD), the most common motor neurodegenerative disorder, lacks a reliable biomarker for early detection. Elevated dopa decarboxylase (DDC) levels show promise as a biomarker for PD, distinguishing it from other neurodegenerative diseases, such as Alzheimer's disease (AD). This perspective explores DDC's regulatory mechanisms, its specificity to PD, and the influence of cofactors like pyridoxal-5-phosphate, tyrosine, and thyroxine on its activity, addressing a critical question: why does elevated DDC not increase dopamine, serotonin, or norepinephrine levels?},
}

@article {pmid42032403,
year = {2026},
author = {Rozanova, NA and Averchuk, AS and Kapkaeva, MR and Zhdankina, VI and Makarov, VI and Skobeltsin, AS and Romanishkin, ID and Baranich, TI and Salmina, AB},
title = {Application of a Three-Cell Blood-Brain Barrier Model to Assess Neurovascular Unit Cell Damage in Alzheimer's Disease.},
journal = {Bulletin of experimental biology and medicine},
volume = {},
number = {},
pages = {},
pmid = {42032403},
issn = {1573-8221},
abstract = {To assess functional characteristics of cells of the neurovascular unit in Alzheimer's disease (AD), we performed differentiation of induced pluripotent stem cells from an AD patient (Alz9L cell line) into neuronal, glial, and endothelial cells with the formation of a three-cell model of the blood-brain barrier (BBB). Increased BBB permeability combined with changes in synaptic plasticity of neurons and changes in the metabolism of endothelial cells was detected in AD. The obtained results confirm the presence of vascular dysfunction during AD development and indicate the possibility of using personalized BBB models to assess the features of barrier formation.},
}

@article {pmid42032417,
year = {2026},
author = {Johny, ST and James, JP and Cherangai, ZF and Vasudevan, R and Vidya, VS and Dixit, S and Parameswaran, S},
title = {In silico design, chemistry and biological activity of thiazole-based azetidinone Schiff bases as potential anti-Alzheimer agents.},
journal = {Journal of computer-aided molecular design},
volume = {40},
number = {1},
pages = {},
pmid = {42032417},
issn = {1573-4951},
}

@article {pmid42032434,
year = {2026},
author = {Choi, DJ and Murali, S and Kwon, W and Woo, J and Song, EC and Ko, Y and Sardar, D and Lozzi, B and Cheng, YT and Williamson, MR and Huang, TW and Sanchez, K and Jankowsky, J and Deneen, B},
title = {Author Correction: Astrocytic Sox9 overexpression in Alzheimer's disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive function.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41593-026-02312-1},
pmid = {42032434},
issn = {1546-1726},
}

@article {pmid42032739,
year = {2026},
author = {Boscheck, H and Luft, M and Mauer, R and Senguel, S and D'elia, Y and Dechent, P and Fliessbach, K and Glanz, W and Hetzer, S and Janowitz, D and Kilimann, I and Kleineidam, L and Kronmüller, M and Lüsebrink, F and Preis, L and Rauchmann, B and Rostamzadeh, A and Schott, BH and Sodenkamp, S and Spruth, E and Stoecklein, S and Yakupov, R and Ziegler, G and Brosseron, F and Buerger, K and Hellmann-Regen, J and Laske, C and Perneczky, R and Peters, O and Priller, J and Ramirez, A and Schneider, A and Spottke, A and Teipel, S and Wiltfang, J and Jessen, F and Düzel, E and Röske, S and Wagner, M and Glöckner, F and Marchant, NL and Klimecki, O and Wirth, M and , },
title = {Pathways to resilience: relationships between cognitive reserve, psychological debt, and Alzheimer's disease biomarkers.},
journal = {Alzheimer's research & therapy},
volume = {18},
number = {1},
pages = {},
pmid = {42032739},
issn = {1758-9193},
}

@article {pmid42032756,
year = {2026},
author = {Trelle, AN and Cody, KA and Nguyen, TT and Winer, JR and Weiss, S and Sai, I and Ward, T and Cheng, G and Channappa, D and Mendiola, J and Al-Rajhi, A and Raghuraman, K and Sha, SJ and Wilson, EN and Wyss-Coray, T and Maecker, HT and Wagner, AD and Mormino, EC},
title = {Plasma proteomic signatures of preclinical Alzheimer's disease in clinically unimpaired older adults.},
journal = {Molecular neurodegeneration},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13024-026-00941-5},
pmid = {42032756},
issn = {1750-1326},
support = {R01AG065255/NH/NIH HHS/United States ; R01AG074339/NH/NIH HHS/United States ; },
}

@article {pmid42032757,
year = {2026},
author = {Ohyagi, M and Ito, M and Yoshimura, A},
title = {Senescence of T cells and organ aging.},
journal = {Inflammation and regeneration},
volume = {46},
number = {1},
pages = {},
pmid = {42032757},
issn = {1880-9693},
abstract = {Senescence of T cells is strongly linked to organismal aging through two interconnected processes: chronic low-grade inflammation and reduced immune surveillance of senescent cells. T cells are particularly vulnerable to thymic involution, hematopoietic stem cell aging, repeated homeostatic proliferation, chronic antigenic stimulation, and metabolic and mitochondrial dysfunction. As a result, aged T cells may lose their capacity to combat infection and eliminate senescent cells, while also contributing to inflammaging through the production of inflammatory cytokines. Recent preclinical studies in murine models have demonstrated that modulation of T-cell immunosenescence can ameliorate age-related diseases. These approaches include PD-1/PD-L1 blockade, senolytic chimeric antigen receptor T (CAR-T) cells, and CXCL4/platelet factor 4 (PF4). In addition, early-stage human clinical studies of caloric restriction, low-dose mTOR inhibition, thymic regeneration, and mesenchymal stromal/stem cell (MSC) therapy suggest that interventions targeting immunosenescence may provide health benefits. Moreover, in murine models of Alzheimer's disease, T cells infiltrating the brain may exert either disease-promoting or protective effects depending on the disease stage, highlighting an important point of intersection between T-cell-mediated immunosenescence and brain aging. This review summarizes the basic concepts of immunosenescence, the molecular basis of immune surveillance of senescent cells, age-associated T-cell subsets, their links to brain aging, and interventional strategies aimed at clinical translation, with particular emphasis on T-cell biology and the transcriptional regulatory network driven by NR4a.},
}

@article {pmid42026254,
year = {2026},
author = {Nakagawa, T and Xie, JL and Park, K and Cao, K and Savadkohighodjanaki, M and Zhang, YJ and Jun, H and Ichii, A and Lee, JY and Soma, S and Medhat, YK and Saido, TC and Igarashi, KM},
title = {Early dopamine disruption in the entorhinal cortex of a knock-in model of Alzheimer's disease.},
journal = {Nature neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42026254},
issn = {1546-1726},
support = {A2019380S//BrightFocus Foundation (BrightFocus)/ ; A2022018F//BrightFocus Foundation (BrightFocus)/ ; BRFSG-2017-04//Brain Research Foundation (BRF)/ ; JPMJPR2481//MEXT | Japan Science and Technology Agency (JST)/ ; AARF-22-923955/ALZ/Alzheimer's Association/United States ; },
abstract = {The entorhinal cortex is a critical brain area for memory formation, while also the region exhibiting the earliest histological and functional alterations in Alzheimer's disease (AD). The entorhinal cortex therefore has been long hypothesized as one of the originating brain areas of AD pathophysiology, although circuit mechanisms causing its selective vulnerability remain poorly understood. Here we show that dopamine neurons projecting their axons to the lateral entorhinal cortex (LEC), critical for memory formation in healthy brains, become dysfunctional from the early pathological stage and cause associative memory impairments in amyloid precursor protein knock-in mice. Dopamine dysfunction led to the disruption of associative memory encoding of LEC layer 2/3. Optogenetic reactivation of LEC dopamine fibers rescued associative learning behavior. L-DOPA treatment restored memory encoding of LEC neurons and associative memory of amyloid precursor protein knock-in mice. These results suggest early dysfunction of LEC-projecting dopamine neurons underlie memory impairment in AD from early stages, pointing to a need for clinical investigation of LEC dopamine in patients with AD.},
}

@article {pmid42026315,
year = {2026},
author = {Manco, C and Righi, D and Sangiorgio, AR and Pucci, B and De Stefano, N and Plantone, D},
title = {Comparison of TDP-43, NfL, and GFAP in cerebrospinal fluid and serum in Alzheimer's disease.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42026315},
issn = {1433-8491},
}

@article {pmid42026319,
year = {2026},
author = {Bdair, M and Zahran, A and Jallad, H and Barham, I and Qubbaj, A and AbuRabi'e, M and Jarrar, B and Aburajab, J and Alsafareeni, Z and Mansor, A and Ghannam, S and Daor, A and Daralbarmeel, A and Awwad, AR and Khader, M and Awawdeh, A},
title = {National trends and disparities in Alzheimer disease's mortality (1999-2023) with scenario projections and a data-driven LSTM sensitivity analysis to 2043.},
journal = {European archives of psychiatry and clinical neuroscience},
volume = {},
number = {},
pages = {},
pmid = {42026319},
issn = {1433-8491},
}

@article {pmid42026378,
year = {2026},
author = {Boregowda, G and Sharif, O and Gutierrez Iii, D and Simmons, A and Pujo-Menjouet, L and Oraby, T and Lindstrom, MR},
title = {Theory and simulations of delayed stochastic and deterministic models of prion diseases.},
journal = {Journal of mathematical biology},
volume = {92},
number = {5},
pages = {},
pmid = {42026378},
issn = {1432-1416},
support = {2316952//National Science Foundation/ ; 2150478//National Science Foundation/ ; ANR-21-CE15-0011//Agence National de la Recherche/ ; },
mesh = {*Prion Diseases/metabolism/etiology/pathology/physiopathology ; Humans ; Stochastic Processes ; Mathematical Concepts ; Computer Simulation ; *Models, Biological ; Brain/metabolism ; Animals ; Connectome ; Disease Progression ; PrPSc Proteins/metabolism ; Models, Neurological ; Prion Proteins ; },
abstract = {Neurodegenerative diseases (NDs), such as Alzheimer's, Parkinson's, and prion diseases, are characterized by the dynamical spread of toxic proteins through the brain. In prion diseases, cellular prion protein (PrP C), produced by neurons, misfolds into a toxic form, known as scrapie prion protein (PrP Sc). PrP Sc induces neuronal stress which ultimately leads to cell death. In this paper, we develop mathematical models for the progression of prion diseases, incorporating a cellular defense mechanism that introduces a delay term affecting protein translation and a volatility term accounting for unaccounted biological factors influencing the system. We also extend the model to capture the spatial spread of toxic proteins over the brain connectome. Our first objective is to establish the existence and uniqueness of a global positive solution to the prion disease models. Afterwards, we analyze the asymptotic behavior of the models by identifying regimes of persistence and extinction of toxic proteins. For the deterministic delayed systems, we perform a stability analysis for the persistence and demonstrate that the system undergoes a Hopf bifurcation. We also study the intensity of fluctuations of the equilibrium state of the stochastic model. Additionally, we present numerical simulations to illustrate the model dynamics using biologically relevant parameters.},
}

*Prion Diseases/metabolism/etiology/pathology/physiopathology
Humans
Stochastic Processes
Mathematical Concepts
Computer Simulation
*Models, Biological
Brain/metabolism
Animals
Connectome
Disease Progression
PrPSc Proteins/metabolism
Models, Neurological
Prion Proteins

@article {pmid42026585,
year = {2026},
author = {Choi, H and Hong, SB and Kim, Y and Joung, H and Choi, Y and Cha, J and Park, JY and Lee, YS and Choi, H and Han, JW and Kim, KH and Shin, CH and Lee, DY and Mook-Jung, I},
title = {Tryptophan-kynurenine metabolic reprogramming along the gut-brain axis alleviates Alzheimer's pathology.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03796-1},
pmid = {42026585},
issn = {1742-2094},
support = {RS-2022-KH128705//Korea Dementia Research Center/ ; RS-2020-KH106747//Korea Dementia Research Center/ ; RS-2023-00273634//National Research Foundation of Korea/ ; },
}

@article {pmid42026650,
year = {2026},
author = {Gabb, VG and Blackman, J and Morrison, HD and Turner, N and Heslegrave, A and Coulthard, E},
title = {Mind the gap: obtaining reliable sleep estimates and the diagnostic value of sleep discrepancy in individuals with Alzheimer's disease and Lewy body disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71377},
doi = {10.1002/alz.71377},
pmid = {42026650},
issn = {1552-5279},
support = {//Bristol and Weston Hospitals Charity/ ; //BRACE/ ; //Alzheimer's Research UK/ ; //Margaret Jost Fellowship/ ; //David Telling Charitable Trust/ ; //Don Thoburn Memorial Scholarship/ ; //S Scobie and A Graham/ ; //NIHR Bristol Biomedical Research Centre/ ; },
mesh = {Humans ; *Lewy Body Disease/complications/diagnosis ; *Alzheimer Disease/complications/diagnosis ; Male ; Female ; Aged ; Actigraphy ; *Sleep Wake Disorders/diagnosis/etiology ; Cognitive Dysfunction/complications ; Aged, 80 and over ; Sleep Quality ; },
abstract = {INTRODUCTION: Objective sleep disturbances, including short and fragmented sleep, are observed in neurodegenerative diseases. However, subjective sleep disturbances are inconsistently reported. Improved understanding of objective and subjective sleep estimation is needed to tailor sleep interventions.

METHODS: Baseline subjective habitual sleep was compared to objective sleep measured by actigraphy averaged over 8 weeks in 20 patients with mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD) or Lewy body disease (LBD) and 20 healthy older adults. Discrepancies between objective and subjective sleep parameters were used to predict cohort membership (AD, LBD, or control).

RESULTS: Participants with AD and LBD estimated lower sleep disturbance than actigraphy. Subjective sleep quality was poorest in LBD and highest in AD. Subjective sleep and subjective-objective sleep discrepancy discriminated between cohorts with 80% accuracy.

DISCUSSION: Subjective and objective sleep differ and both should be measured in MCI and dementia. Sleep discrepancy may have diagnostic utility.},
}

Humans
*Lewy Body Disease/complications/diagnosis
*Alzheimer Disease/complications/diagnosis
Male
Female
Aged
Actigraphy
*Sleep Wake Disorders/diagnosis/etiology
Cognitive Dysfunction/complications
Aged, 80 and over
Sleep Quality

@article {pmid42026653,
year = {2026},
author = {Acarsoy, C and Bos, D and Mooldijk, SS and Ikram, MA and Ikram, MK},
title = {Migraine and the Risk of Dementia in the General Population.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71386},
doi = {10.1002/alz.71386},
pmid = {42026653},
issn = {1552-5279},
support = {//Erasmus Medical Center and Erasmus University/ ; //Organization for Scientific Research/ ; //Netherlands Organization for Health Research and Development/ ; //Research Institute for Diseases in the Elderly/ ; //Netherlands Genomics Initiative/ ; //Ministry of Education, Culture and Science/ ; //Ministry for Health, Welfare and Sports/ ; //European Commission/ ; //Municipality of Rotterdam/ ; },
mesh = {Humans ; *Migraine Disorders/epidemiology ; Female ; Male ; *Dementia/epidemiology ; Aged ; Prospective Studies ; Risk Factors ; Middle Aged ; Netherlands/epidemiology ; Alzheimer Disease/epidemiology ; Surveys and Questionnaires ; },
abstract = {INTRODUCTION: Migraine and dementia are prevalent disorders with high societal impact; however, research regarding their association remains inconsistent.

METHODS: We analyzed 6888 participants from the prospective Rotterdam Study. Migraine status was assessed (2006-2011) via validated questionnaire. Participants were followed for a median of 9.4 years until January 2020. Dementia diagnoses were confirmed through in-person screenings and medical record linkages, including neuroimaging.

RESULTS: At baseline, 1041 participants (15.1%) had migraine. Over 62,180 person-years, 491 participants developed dementia (379 [77.2%] with Alzheimer's). Cox models revealed that migraine was associated with a lower risk of dementia (hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.51-0.95) and Alzheimer's disease (HR 0.58, 95% CI: 0.40-0.85).

DISCUSSION: This study suggests that migraine is associated with a reduced risk of dementia, including Alzheimer's disease. Whether this reflects biological neuroprotection or methodological factors is currently unclear, necessitating further investigation.},
}

Humans
*Migraine Disorders/epidemiology
Female
Male
*Dementia/epidemiology
Aged
Prospective Studies
Risk Factors
Middle Aged
Netherlands/epidemiology
Alzheimer Disease/epidemiology
Surveys and Questionnaires

@article {pmid42026661,
year = {2026},
author = {Kuppens, A and Rogister, B and Neirinckx, V},
title = {Pharmacological modulation of CXCL12/CXCR4/ACKR3 for brain disorders - an overview.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-026-02877-1},
pmid = {42026661},
issn = {1478-811X},
support = {7.6518.24//Fonds De La Recherche Scientifique - FNRS/ ; },
}

@article {pmid42026868,
year = {2026},
author = {Huang, J and Wang, YB and Wu, J and Qian, PJ and Shao, J and Cao, DD and Liu, Y and Luo, ZG},
title = {SEC62-mediated ER-Phagy activation alleviates Alzheimer's disease pathology and restores cognitive function in 5×FAD mice.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.04.037},
pmid = {42026868},
issn = {1525-0024},
abstract = {Alzheimer's disease (AD) is a common age-related neurodegenerative disorder. Previous studies have shown that patients with AD exhibit dysregulation of endoplasmic reticulum (ER) homeostasis in the brain, such as ER stress and ER damage. As a type of selective autophagy that specifically clears damaged ER, ER-phagy (endoplasmic reticulum-phagy) plays a key role in ER quality control, but the role in AD progression remains elusive. In this study, we found that ER homeostasis is severely disrupted in the pathological state of AD, characterized by enhanced ER stress response, the presence of ER damage, and concurrent defects in ER-phagy function. Notably, some receptors mediating ER-phagy were decreased in neurons differentiated from induced pluripotent stem cells (iPSCs) derived from AD patients and in 5×FAD mouse samples. Interestingly, overexpression of the ER-phagy receptor SEC62 in the brain of 5×FAD mice via intrathecal AAV injection markedly alleviated disease phenotypes, including β-amyloid (Aβ) plaque deposition, neuroinflammation, and cognitive impairment. These results indicate that restoring ER-phagy activity provides a potential strategy for the treatment of AD.},
}

@article {pmid42027189,
year = {2026},
author = {Aaltonen, A and Saari, TT and Urjansson, M and Palviainen, T and Paajanen, TI and FinnGen, and Palotie, A and Runz, H and Kaprio, J and Julkunen, V and Vuoksimaa, E},
title = {Cross-sectional assessment of telephone- and computer-administered instruments in detection of cognitive impairment.},
journal = {Journal of clinical and experimental neuropsychology},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/13803395.2026.2661625},
pmid = {42027189},
issn = {1744-411X},
abstract = {OBJECTIVE: We investigated the associations of telephone- and computer-administered cognitive screening instruments for Alzheimer's disease with in-person measurement in a population-based sample of individuals without a prior diagnosis of dementia-causing neurodegenerative disease.

METHOD: We studied 202 TWINGEN participants (126 female) who had in-person administered Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-nb) data. The participants were aged 65-85 years and of European ancestry. Telephone-administered instruments were telephone assessment for dementia (TELE) and modified version of Telephone Tnterview for Cognitive Status, and computer-administered instrument was web-based cCOG. We utilized correlation analyses, areas under the receiver operating characteristic curves (AUC) and hierarchical linear mixed-effects models in main analyses.

RESULTS: Screening instruments exhibited moderate to high correlations with CERAD-nb, with the strongest correlation between cCOG and CERAD-nb (r = .62). Despite exclusion criteria, 20 participants had cognitive impairment according to the CERAD-nb total score. When evaluating the instruments' ability to distinguish between participants with and without cognitive impairment, AUCs ranged from .65 (95% CI [.53, .78]) for TELE to .76 (95% CI [.67, .86]) for cCOG. All instruments predicted in-person CERAD-nb score in linear mixed-effects models, when controlling for demographic factors. Including both telephone- and computer-administered measures as predictors resulted in better accuracy compared to including only one modality as a predictor.

CONCLUSIONS: Performance in telephone- and computer-administered cognitive screening instruments was associated with performance in in-person neuropsychological battery designed for early detection of Alzheimer's disease. The results indicate validity of the computerized and telephone-administered tests at the population level.},
}

@article {pmid42027251,
year = {2026},
author = {Alghamdi, M and von Wegner, F and Chan, DKY and Green, M and , },
title = {Brain atrophy and clinical diagnosis independently predict default mode network failure across the Alzheimer's disease continuum.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {},
pages = {e70343},
pmid = {42027251},
issn = {2352-8729},
abstract = {INTRODUCTION: This study examined the link between default mode network (DMN) functional connectivity, cerebral small vessel disease (CSVD), brain atrophy, and plasma Alzheimer's disease (AD) biomarkers.

METHODS: We analyzed the Alzheimer's Disease Neuroimaging Initiative database (N = 279), examining the relationships between DMN functional integrity (network failure quotient [NFQ]), gray and white matter fractions (GMF, WMF), white matter hyperintensities (WMHs), plasma phosphorylated tau (p-tau)217 and amyloid beta (Aβ)42/Aβ40 ratio, and clinical assessments. Statistical associations were tested using one-way analysis of variance and univariate and multivariate regression models.

RESULTS: The AD group showed increased NFQ values (P < 0.001). Significant univariate associations were found between NFQ and WMH, gray and white matter atrophy, Aβ ratio, and p-tau217 (P < 0.05). Atrophy markers (GMF, WMF) and AD diagnosis were the only independent predictors of NFQ in multivariate models (P < 0.05).

DISCUSSION: Our study identifies markers of brain atrophy as independent predictors of DMN failure, unlike AD plasma biomarkers and magnetic resonance imaging markers of CSVD.},
}

@article {pmid42027297,
year = {2026},
author = {Chen, W and Li, R and Zhang, J and Lei, J and Jiang, X and Sun, X},
title = {From metabolic substrate to epigenetic regulation: roles and mechanisms of lactylation in brain health and disease.},
journal = {Frontiers in molecular neuroscience},
volume = {19},
number = {},
pages = {1779468},
pmid = {42027297},
issn = {1662-5099},
abstract = {Lactate, traditionally regarded as a metabolic byproduct of glycolysis, is now recognized as a critical signaling molecule in the central nervous system. Emerging evidence indicates that lactate participates in a dynamic metabolic-epigenetic regulatory network through protein lactylation, a post-translational modification capable of modulating chromatin structure and gene transcription. We summarize the physiological roles of lactate in neuronal-glial metabolic coupling and highlight cell-type-specific functions of the lactate-lactylation axis under both normal and pathological conditions. Particular emphasis is placed on its involvement in ischemic stroke, neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Available findings indicate that this axis is integral to synaptic plasticity, neuroinflammatory balance, and metabolic homeostasis. Under pathological conditions, excessive lactate accumulation promotes aberrant lactylation patterns that may drive persistent inflammation, metabolic reprogramming, and neuronal dysfunction by reshaping chromatin accessibility and transcriptional landscapes. Collectively, the lactate-lactylation axis represents a unifying mechanistic framework linking metabolic flux to epigenetic regulation in neurological disorders and may serve as a promising source of diagnostic biomarkers and precision therapeutic targets.},
}

@article {pmid42027568,
year = {2026},
author = {Feng, ZT and Zhang, YY and Xue, CX},
title = {Bioactive compounds and exercise in aging and neurodegeneration: mechanistic insights from the gut-brain-metabolic axis.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1781176},
pmid = {42027568},
issn = {2296-861X},
abstract = {Aging and neurodegenerative disorders are associated with impaired hippocampal plasticity, yet existing literature largely examines exercise, nutrition, or metabolic regulation in isolation. This review synthesizes emerging evidence supporting an integrative neuro-nutritional-metabolic framework in which bioactive compounds and physical exercise converge to modulate hippocampal neurogenesis, synaptic plasticity, and cognitive resilience. Recent investigative efforts elucidate the neuro-nutritional-metabolic axis as a pivotal interface that integrates bioactive compounds derived from diet, systemic metabolic processes, and neuronal functionality. In this review, the term 'neuro-nutritional-metabolic axis' refers to an integrative framework describing the bidirectional interactions among dietary bioactive compounds, systemic metabolic regulation, and central nervous system plasticity. This concept extends established models such as the microbiota-gut-brain axis and muscle-brain communication by emphasizing their convergence on metabolic and neurotrophic signaling pathways relevant to hippocampal function. Simultaneously, physical exercise is acknowledged as a significant modulator of neurotrophic signaling pathways, mitochondrial performance, and neuroinflammatory responses. This review synthesizes mechanistic evidence derived predominantly from preclinical studies alongside emerging but comparatively limited clinical findings to evaluate how bioactive compounds and physical exercise interact to influence hippocampal plasticity and cognitive function. We examine the convergence of these interventions on essential molecular pathways, as well as antioxidant and anti-inflammatory cascades, to facilitate neuronal survival, synaptic reorganization, and cognitive resilience. Moreover, we investigate their potential to mitigate metabolic dysfunction, oxidative stress, and chronic inflammation, which are pivotal factors contributing to cognitive deterioration in the context of aging and neurodegenerative conditions such as Alzheimer's and Parkinson's disease. Comprehending these synergistic interactions lays the groundwork for formulating tailored, multimodal interventions that specifically address the neuro-nutritional-metabolic axis to enhance memory retention, optimize learning processes, and support cognitive resilience and may contribute to the modulation of risk factors associated with neurodegenerative conditions.},
}

@article {pmid42027570,
year = {2026},
author = {Zhang, H and Liu, C and Yuan, X and Yin, H},
title = {The role of nutrition and multimodal lifestyle interventions in Alzheimer's prevention and management: a mini-review.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1818913},
pmid = {42027570},
issn = {2296-861X},
abstract = {Alzheimer's disease (AD) is a progressive and currently incurable neurodegenerative disorder, which is driving a paradigm shift in research focus toward preventive and disease-modifying strategies. This mini-review synthesizes current evidence on dietary and lifestyle interventions for AD prevention and management from randomized controlled trials (RCTs) and observational studies. Current findings indicate that multidomain approaches, such as the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and the Finnish Geriatric Intervention Study (FINGER) model, which integrate nutrition, physical activity, and cognitive training, consistently demonstrate efficacy in slowing cognitive decline and reducing brain atrophy in at-risk elderly populations. The evidence for specific nutritional supplements is mixed; however, certain combinations like omega-3 fatty acids paired with carotenoids, B vitamins (folate/B12), and probiotics show promise, particularly for improving memory and reducing inflammation. Intervention outcomes are significantly influenced by genetic factors, especially the APOE4 carrier status, which modulates nutrient metabolism and amyloid response, thereby underscoring the critical need for personalized approaches. Key targeted biological pathways include oxidative stress, phospholipid metabolism, and neuro-inflammation. Despite promising data, several limitations persist, such as inconsistent results, short trial durations, and a lack of standardized protocols. Future research must prioritize long-term, genetically stratified trials alongside mechanistic studies to validate efficacy, optimize personalization, and translate findings into clinically actionable, scalable guidelines for diverse populations.},
}

@article {pmid42027686,
year = {2026},
author = {Jeon, JY and Lee, H and Ji, M and Kim, JS and Ahn, DH},
title = {Personalized audiovisual gamma stimulation enhances neural connectivity and entrainment beyond fixed 40 Hz protocols.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1787255},
pmid = {42027686},
issn = {1662-4548},
abstract = {BACKGROUND: Conventional 40 Hz gamma stimulation is applied across individuals, potentially overlooking inter-individual neural variability.

OBJECTIVE: This study evaluated conversation gamma frequency (CGF)-a personalized gamma frequency derived from task engagement-against the fixed 40 Hz and individual gamma frequency (IGF) derived from auditory responses.

METHODS: In Experiment 1, gamma center frequencies were measured under resting, reading, and conversation conditions. In Experiment 2, EEG was used to compare neural entrainment effects across CGF, 40 Hz, and IGF conditions.

RESULTS: Conversation gamma frequency stimulation induced stronger neural activation and functional connectivity in the frontal, temporal, and parietal cortices compared to 40 Hz or IGF. Theta-gamma coupling analysis revealed significantly increased phase synchronization under CGF compared to 40 Hz with enhanced connectivity. However, entrainment declined as the frequency difference between CGF, and 40 Hz increased, emphasizing the limitation of fixed-frequency stimulation.

CONCLUSION: These findings provide EEG-based mechanistic evidence that individualized gamma stimulation may represent a hypothesis-generating strategy for future neurorehabilitation research in aging and neurodegenerative conditions.},
}

@article {pmid42027759,
year = {2026},
author = {Han, Y and Luo, G and Huang, Y and Cai, Z and Su, W and Kuang, X and Huang, L and Wei, L and Ming, F and He, Z and Yang, Z and Wang, J and Jiang, W and Xiao, C and Hu, Q and Yan, J},
title = {Research progress on Alzheimer's disease vaccines: from Aβ-targeted approaches to clinical translation.},
journal = {Frontiers in aging},
volume = {7},
number = {},
pages = {1794820},
pmid = {42027759},
issn = {2673-6217},
abstract = {BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive impairment, with the β-amyloid protein (Aβ) aggregation as a core pathological driver. As global aging intensifies, AD poses a severe public health burden, highlighting the urgency of developing effective immunotherapies. This review aims to systematically summarize the research progress of Aβ-targeted AD vaccines, from first-generation approaches to next-generation strategies, and discuss key challenges and future directions for clinical translation.

METHODS: A comprehensive literature search was conducted across PubMed, Web of Science, the Cochrane Library, EMBASE, and Google Scholar up to 14 November 2025. Relevant studies were selected using predefined eligibility criteria, focusing on Aβ-targeted AD vaccines' development, mechanisms, preclinical efficacy, and clinical outcomes. Review articles and meta-analyses were included, while case reports and non-Aβ-targeted studies were excluded. Data extraction and synthesis focused on vaccine strategies, immune mechanisms, and translational challenges.

RESULTS: First-generation Aβ vaccine (e.g., AN-1792) showed preclinical promise but failed clinically due to autoimmune complications. Next-generation vaccines, including peptide/epitope vaccines, DNA vaccines, viral vector vaccines, and protein self-assembling vaccines, have been developed to induce protective Th2-biased immune responses while avoiding harmful T-cell reactions. Preclinical studies demonstrate reduced Aβ deposition and improved cognitive function, with several candidates advancing to clinical trials showing favorable safety and immunogenicity. Key mechanisms include Fc receptor-mediated phagocytosis, antibody-mediated fibril disaggregation, and the peripheral Aβ sink effect.

CONCLUSION: Aβ-targeted AD vaccines have evolved toward safer and more effective designs, with multiple strategies showing translational potential. Challenges remain, including blood-brain barrier (BBB) penetration, immune response modulation, and defining optimal therapeutic time windows. Future research should focus on personalized vaccines, combination therapies, and novel antigen delivery platforms to fully realize the clinical potential of AD immunotherapies.},
}

@article {pmid42027884,
year = {2026},
author = {Naik, DR and Savyanavar, DA},
title = {Comparative Analysis of Deep Learning Techniques in Alzheimer's Disease Diagnosis: Trends, Challenges, and Future Directions.},
journal = {MethodsX},
volume = {16},
number = {},
pages = {103844},
pmid = {42027884},
issn = {2215-0161},
abstract = {Alzheimer's disease is a slow, progressive neurological disorder that impacts the brain tissue and causes cells to die, the most common reason for dementia. It typically reduces brain volume, subsequently impairing several cognitive functions. We explored the phases of Alzheimer's disease diagnosis by thoroughly analysing the paper and highlighting the significance of pre-processing methods. Artificial intelligence progress has transformed medical image analysis by enabling automatic, precise identification of Alzheimer's disease through hybrid architectures, convolutional neural networks, and transfer-learning-based models. This article includes applications of Alzheimer's disease based on datasets, Artificial Intelligence models, limitations, pre-processing methods, challenges, and current research in this area. The article lists various medicinal modalities, risk factors for Alzheimer's disease, the disease's progression stages, and different criteria for evaluating the performance of Artificial Intelligence models. Accuracy, precision, confusion matrix, AUC, F1-score, ROC, recall, and MCC are some of the metrics covered in this paper. The paper discusses the number of comparisons of various deep learning techniques for Alzheimer's, new trends, limitations, recommendations, and future directions. Finally, the paper shows the ongoing practical outcomes and difficulties in Alzheimer's situations. Building on the analysis, this survey helps to cover different dimensions of Alzheimer's disease that have not been previously considered.},
}

@article {pmid42027916,
year = {2026},
author = {Xu, F and Zhang, Y and Tan, D and He, Y and Fei, Q and Xu, K},
title = {Effects of exercise on cognitive function in older patients with Alzheimer's disease: a meta-regression and meta-analysis.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1793973},
pmid = {42027916},
issn = {2296-2565},
mesh = {Humans ; *Alzheimer Disease/therapy/psychology ; *Cognition/physiology ; Aged ; *Exercise/psychology/physiology ; *Exercise Therapy/methods ; Middle Aged ; Male ; Randomized Controlled Trials as Topic ; Female ; },
abstract = {OBJECTIVE: This study aimed to systematically evaluate the effects of exercise intervention on cognitive function in AD patients through meta-analysis, specifically investigating the dose-response relationships and moderating effects of various exercise prescription parameters including frequency, single-session duration, weekly total duration, total intervention duration, type, and intensity-on the magnitude of cognitive improvement. The findings are expected to provide scientific and actionable empirical evidence for designing precise and individualized exercise programs.

METHODS: Relevant literatures were systematically retrieved from eight databases up to August 2025, including PubMed, Web of Science, Embase, Emcare, Scopus, Cochrane Library, Ebsco, and SPORTDiscus. All included trials were randomized controlled trials (RCTs) involving adults aged 60 years and above. These studies examined the effects of exercise intervention on cognitive function in AD patients, compared with passive control groups without exercise. A multilevel meta-analysis was used to assess the impact of exercise on cognitive function outcomes in AD patients. Additionally, multivariate meta-regression analysis was employed to identify the exercise frequency (sessions per week) that maximizes cognitive improvement, as well as key moderating factors.

RESULTS: Data from 23 studies, involving 1,868 adults, were included. Exercise intervention significantly improved global cognitive function in AD patients (g = 0.22, 95% CI: 0.02-0.41, p < 0.001). Patient age, single-session duration, and total weekly exercise duration did not significantly affect outcomes (p > 0.05). However, the cognitive benefits of exercise were significantly enhanced with increased weekly exercise frequency, with a notable strengthening trend observed when sessions exceeded five per week.

CONCLUSION: Exercise intervention can effectively improve cognitive function in AD patients. "To optimize intervention outcomes, exercise prescription should consider higher frequency (e.g., more than five sessions per week may be associated with greater cognitive benefits) and the cumulative effect during the initial intervention phase (e.g., sustained beyond 12 weeks may represent a critical window for short-term improvement). In addition, a potential plateau in long-term benefits suggests the need for periodic program adjustments and multimodal exercise strategies. These findings should be interpreted as exploratory dose-response associations rather than definitive clinical prescriptions.

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1012816, identifier CRD420251012816.},
}

Humans
*Alzheimer Disease/therapy/psychology
*Cognition/physiology
Aged
*Exercise/psychology/physiology
*Exercise Therapy/methods
Middle Aged
Male
Randomized Controlled Trials as Topic
Female

@article {pmid42028071,
year = {2026},
author = {Sun, X and Yang, L and Wang, X},
title = {Traditional Chinese Medicine for Alzheimer's Disease: Current Evidence and Chemometric Approaches for Multi-Target Evaluation.},
journal = {Neuropsychiatric disease and treatment},
volume = {22},
number = {},
pages = {590661},
pmid = {42028071},
issn = {1176-6328},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is currently no therapy that can fundamentally change the disease course. The limitations of single-target drugs have led the scientific community to turn to multi-target intervention strategies. In this context, traditional Chinese medicine (TCM) demonstrates potential in addressing the complex pathology of AD due to its "multi-component, multi-target, multi-pathway" overall regulatory characteristics. This review systematically reviews the current research status of TCM in the treatment of AD, with a particular focus on the evidence of its effects through multiple mechanisms such as reducing Aβ deposition, inhibiting excessive phosphorylation of Tau protein, regulating the cholinergic system, and alleviating neuroinflammation. Additionally, this article highlights how to utilize the "spectral efficacy relationship" combined with chemometrics methods (such as multiple regression, partial least squares regression, artificial neural networks, etc) to establish quantitative correlations between TCM chemical components and efficacy/clinical endpoints, thereby providing a methodological framework for evaluating the synergistic effects of TCM's multi-component interactions. The article also summarizes the evidence grades of currently commonly used TCM preparations in clinical practice and points out that future research needs to continuously deepen in areas such as standardized clinical endpoints, strict trial design, systematic safety assessment, and data-driven efficacy analysis. This review aims to provide theoretical references and research directions for integrating the holistic view of TCM with modern system analysis methods and promoting the development of multi-target treatment strategies for AD.},
}

@article {pmid42028213,
year = {2026},
author = {Medina-Rioja, R and Llorente-Vidrio, A and Ruiz-Garcia, R and Rodríguez-Violante, M},
title = {From clinical judgment to biology: a clinician's opinion on the use of blood-based biomarkers in Alzheimer's disease.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1804163},
pmid = {42028213},
issn = {1664-2295},
}

@article {pmid42028229,
year = {2026},
author = {Zhu, Y and Singh, RK and Bekena, S and Brown, DC and Chen, C and Blake, M and Trani, JF and Babulal, GM},
title = {Lost before forgetting: objective driving metrics track navigation deficits tied to preclinical Alzheimer's disease.},
journal = {Innovation in aging},
volume = {10},
number = {5},
pages = {igag013},
pmid = {42028229},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: Navigation is a complex, multisensory process in which subtle changes may emerge before the onset of symptomatic Alzheimer's disease (AD). This study investigated whether navigation abilities were associated with amyloid and tau pathology in cognitively normal older adults.

RESEARCH DESIGN AND METHODS: Among 285 cognitively unimpaired older adults, navigation and objective driving behaviors were assessed using the self-reported Santa Barbara Sense of Direction Scale (SBSOD) and a datalogger, respectively. Amyloid and tau burden were quantified using PET-MRI 2 years post-initial driving data collection. Linear mixed-effects models were used to evaluate the associations between biomarker status and longitudinal navigation changes.

RESULTS: At baseline, there were no significant differences in SBSOD, trip chaining, or entropy, a metric that quantifies the variability in one's driving patterns based on PET biomarker status. Over 6.1 years (SD = 3.3), compared to amyloid- participants, amyloid+ participants experienced faster declines in SBSOD and entropy and increases in trip chain counts and percentages of chained trips/distances, indicating more deliberate compensatory planning for subtle deficits. Conversely, tau+ participants exhibited slower declines in SBSOD and greater increases in driving unpredictability (i.e., higher entropy, greater percentages of chained trips/distances) across 5.6 years (SD = 2.9), but not in total trip counts compared to tau- participants.

DISCUSSION AND IMPLICATIONS: Changes in navigation may reflect the accumulation of amyloid (compensatory planning) and tau (diminished planning, increased randomness) in distinct brain regions. These findings highlight the promise of driving and navigation metrics as sensitive, noninvasive markers of preclinical AD, underscoring a critical window for intervention.},
}

@article {pmid42028802,
year = {2026},
author = {Chan, CK and Glover, CM and Parker, M and Grill, JD and Langbaum, JB and Morhardt, DJ and Okonkwo, O and Farrar-Edwards, D and Wang, S},
title = {Outreach, Recruitment and Engagement Cores of NIA-designated Alzheimer's Disease Research Centers: Current strategies and future directions.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71238},
doi = {10.1002/alz.71238},
pmid = {42028802},
issn = {1552-5279},
support = {P30AG072959 (C.K.C.)//National Institutes of Health/National Institute on Aging/ ; P30AG072976 (S.W.)//National Institutes of Health/National Institute on Aging/ ; 5P50AG016573 (C.M.G.)//National Institutes of Health/National Institute on Aging/ ; P30AG066511 (M.P.)//National Institutes of Health/National Institute on Aging/ ; P30AG072980 (J.B.L.)//National Institutes of Health/National Institute on Aging/ ; P30AG066519 (J.D.G.)//National Institutes of Health/National Institute on Aging/ ; P30AG013854 (D.J.M.)//National Institutes of Health/National Institute on Aging/ ; P30AG062715 (O.O. D.F.E.)//National Institutes of Health/National Institute on Aging/ ; },
mesh = {Humans ; *Alzheimer Disease ; United States ; *National Institute on Aging (U.S.) ; *Patient Selection ; *Biomedical Research ; },
abstract = {Populations at higher risk for Alzheimer's disease and related dementias (ADRD) are often not proportionally represented in research. These populations include but are not limited to individuals from wide-ranging ethnic and racial backgrounds, those with lower education, and those with limited health-care access. Addressing disparities in research participation will be essential to improving our understanding of the varied causal mechanisms, risks and protective factors, and responses to interventions to find generalizable solutions to improve health outcomes in ADRD. The goals of this perspective are to (1) review obstacles and facilitators to recruitment and retention of populations at higher risk for ADRD, (2) provide an overview of data-driven actionable items, ongoing strategies, and proposed initiatives for the recruitment and retention of these populations in National Institute on Aging-funded Alzheimer's Disease Research Centers; and (3) highlight the roles of Outreach, Recruitment and Engagement Cores and the National Alzheimer's Coordinating Center in achieving these goals.},
}

Humans
*Alzheimer Disease
United States
*National Institute on Aging (U.S.)
*Patient Selection
*Biomedical Research

@article {pmid42028856,
year = {2026},
author = {Wang, J and Xu, L and Shen, Q and Tang, Y},
title = {GABAB receptors in glial cells: from physiological regulation to pathological implications.},
journal = {Brain : a journal of neurology},
volume = {},
number = {},
pages = {},
doi = {10.1093/brain/awag141},
pmid = {42028856},
issn = {1460-2156},
abstract = {The GABAB receptor, a metabotropic receptor for the inhibitory neurotransmitter γ-aminobutyric acid, is essential for the proper functioning of inhibitory neurons. Previous studies have shown that GABAB receptors are primarily expressed at presynaptic or postsynaptic membranes of inhibitory or excitatory neurons, where they play a critical role in regulating synaptic signaling. Interestingly, a growing body of evidence indicates that GABAB receptors are also expressed in various types of glial cells and can significantly influence their functions, ultimately contributing to the regulation of multiple processes in the central nervous system. In this review, we first summarize the structure of GABAB receptors and their common downstream signaling pathways in neuronal and glial cells. We then highlight recent research progresses about how GABAB receptors in different glial cell types participate in regulating various important physiological processes, such as excitatory/inhibitory balance, synaptic pruning, and myelination. Furthermore, we provide a comprehensive overview of the significant roles played by glial GABAB receptors in the pathogenesis of neurological disorders, including epilepsy, inflammatory diseases, Alzheimer's disease, major depressive disorder, cerebrovascular diseases, and multiple sclerosis. Accumulating evidence indicates that glial GABAB receptors play a pivotal role in both health and disease, highlighting their potential as therapeutic targets for a variety of neurological conditions. By comprehensively outlining the multiple physiological and pathological processes mediated by GABAB receptors in brain glial cells, this review seeks to broaden the functional scope of glial cells and enhance the comprehension of neuron-glia crosstalk.},
}

@article {pmid42029167,
year = {2026},
author = {Huo, M and Tran, RT and Meyer, OL and Lyons, KS and Mroz, EL},
title = {Spousal Discrepancies in Perceived Needs of People Living with Alzheimer's Disease: A Mixed-Methods Study of Caregivers' Perspective Taking and Dyadic Communication.},
journal = {Journal of applied gerontology : the official journal of the Southern Gerontological Society},
volume = {},
number = {},
pages = {7334648261446038},
doi = {10.1177/07334648261446038},
pmid = {42029167},
issn = {1552-4523},
abstract = {People living with Alzheimer's disease (PLWD) often face unmet care needs, which may arise as caregivers and PLWD differ in their perceptions of PLWD's needs. To understand how these discrepancies vary by caregivers' perspective taking (i.e., their ability to understand PLWD's thoughts and feelings), we conducted a sequential mixed-methods study with 67 couples managing Alzheimer's disease. Both spouses completed semi-structured interviews to describe PLWD's needs and discussed how they communicated about needs. Caregivers' perspective taking was negatively associated with discrepancies in PLWD's needs. Thematic analysis of a subgroup parallel sample demonstrated that, when caregivers reported high perspective taking, couples described navigating PLWD's needs through open dialogue and caregivers adopted respectful communication practices. When caregivers reported low perspective taking, couples described misaligned expectations and communication efforts; caregivers initiated communication to identify PLWD needs and acknowledged employing insensitive language. Findings can inform interventions to improve the quality of dementia care and promote health.},
}

@article {pmid42029189,
year = {2026},
author = {Furman, S and Zayou, L and Tsourmas, KI and Javonillo, DI and Olivarria, GM and Cheng, Y and Pachow, C and Fernandez, K and Le, L and Edwards, RA and Nicholas, DA and Sanchez, GP and Baric, RS and Green, KN and Lane, TE},
title = {Infection of 5xFAD mice with a mouse-adapted SARS-CoV-2 does not alter Alzheimer's disease neuropathology yet induces widespread changes in gene expression across diverse cell types.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71394},
doi = {10.1002/alz.71394},
pmid = {42029189},
issn = {1552-5279},
support = {R35NS116835//National Institutes of Health (NIH-National Institute of Neurological Disorder and Stroke [NINDS])/ ; R01AG081599//NIH-National Institute on Aging (NIA)/ ; U54 AG054349/AG/NIA NIH HHS/United States ; R01 AI110700/AI/NIAID NIH HHS/United States ; 5P30CA062203-26//NIH-National Cancer Institute (NCI)/ ; U01AI180164//NIH-National Cancer Institute (NCI)/ ; 1F31NS141599//NIH-National Cancer Institute (NCI)/ ; T32 NS121727/NS/NINDS NIH HHS/United States ; 5T32 AI007319-33//NIH-National Cancer Institute (NCI)/ ; T32 AG00096//NIH-NIA Training/ ; U54 AG054349/AG/NIA NIH HHS/United States ; T32 NS121727/NS/NINDS NIH HHS/United States ; 105190/ALZ/Alzheimer's Association/United States ; },
mesh = {Animals ; *Alzheimer Disease/pathology/genetics/virology/metabolism ; Mice ; *COVID-19/pathology/genetics ; Mice, Transgenic ; *Brain/pathology/metabolism/virology ; *SARS-CoV-2 ; Disease Models, Animal ; Plaque, Amyloid/pathology ; Neuroglia/metabolism ; Neurons/metabolism/pathology ; Amyloid beta-Peptides/metabolism ; Humans ; Gene Expression ; },
abstract = {INTRODUCTION: The COVID-19 pandemic underscored the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on worsening the severity of Alzheimer's disease (AD) neuropathology and disease progression.

METHODS: Aged 5xFAD and wild-type (WT) mice were infected with a mouse-adapted SARS-CoV-2 (MA10), and extensive characterization of molecular and cellular changes within the brains was carried out.

RESULTS: MA10 infection induced acute viral pneumonia. Viral RNA was undetectable within the brains of infected mice, and there was no evidence of glial activation or neuroinflammation. MA10 infection did not affect amyloid beta (Aβ) plaque volume or numbers in 5xFAD mice compared to uninfected mice. Spatial transcriptomics revealed altered expression of genes associated with homeostatic function in neurons, glia, and vascular endothelial cells.

DISCUSSION: Collectively, these findings demonstrate that while MA10 infection did not affect AD neuropathology, there were numerous downstream effects on gene expression associated with resident central nervous system cell functions that may impact neurologic disease.},
}

Animals
*Alzheimer Disease/pathology/genetics/virology/metabolism
Mice
*COVID-19/pathology/genetics
Mice, Transgenic
*Brain/pathology/metabolism/virology
*SARS-CoV-2
Disease Models, Animal
Plaque, Amyloid/pathology
Neuroglia/metabolism
Neurons/metabolism/pathology
Amyloid beta-Peptides/metabolism
Humans
Gene Expression

@article {pmid42029395,
year = {2026},
author = {Deng, W and Xie, Y},
title = {Beyond AUC: Clinical interpretability of depression-MRI-machine learning analyses in Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71435},
doi = {10.1002/alz.71435},
pmid = {42029395},
issn = {1552-5279},
}

@article {pmid42029407,
year = {2026},
author = {Wearn, A and Onuska, KM and Shanks, HRC and Gaurav, R and Lehéricy, S and Baracchini, G and Hughes, C and Tremblay-Mercier, J and Narayanan, S and Breitner, J and Poirier, J and Schmitz, TW and Turner, GR and Spreng, RN and , },
title = {Locus coeruleus degeneration is associated with cortical tau deposition and cognitive decline in older adults at familial risk of Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71427},
doi = {10.1002/alz.71427},
pmid = {42029407},
issn = {1552-5279},
support = {R01(RNS: AG068563)/AG/NIA NIH HHS/United States ; RNS: AARG-22-927100/ALZ/Alzheimer's Association/United States ; AW #317644 CSH: #320680 RNS//Fonds de Recherche du Québec-Santé/ ; CSH: #181831/CAPMC/CIHR/Canada ; //McGill University: JeanneTimminsCostelloPostdoctoralFellowship(AW)/ ; },
mesh = {Humans ; *Locus Coeruleus/pathology/diagnostic imaging/metabolism ; *Alzheimer Disease/pathology/diagnostic imaging/genetics/metabolism ; Male ; Female ; *tau Proteins/metabolism ; Aged ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Neuropsychological Tests ; Longitudinal Studies ; *Cognitive Dysfunction/diagnostic imaging/pathology ; Aged, 80 and over ; Middle Aged ; Melanins ; },
abstract = {INTRODUCTION: The locus coeruleus (LC) is among the first sites of tau pathology in Alzheimer's disease (AD) and may seed neocortical tau.

METHODS: We used longitudinal neuromelanin-sensitive MRI to assess LC integrity in vivo in a cohort of cognitively unimpaired older adults with familial risk of AD in relation to tau and amyloid positron emission tomography (PET) and long-term cognitive trajectories.

RESULTS: We showed that both LC integrity at baseline and its rate of degeneration over time independently predicted a neocortical pattern of tau deposition. In keeping with the known function of the LC, neuropsychological tests showed that LC integrity at baseline predicted changes in attention. Finally, we found that longitudinal LC degeneration correlated with memory decline in people with elevated neocortical amyloid burden.

DISCUSSION: Our findings underscore the importance of LC in AD pathogenesis. Longitudinal measurement of LC degeneration may help distinguish trajectories of age-related cognitive decline and early AD.},
}

Humans
*Locus Coeruleus/pathology/diagnostic imaging/metabolism
*Alzheimer Disease/pathology/diagnostic imaging/genetics/metabolism
Male
Female
*tau Proteins/metabolism
Aged
Positron-Emission Tomography
Magnetic Resonance Imaging
Neuropsychological Tests
Longitudinal Studies
*Cognitive Dysfunction/diagnostic imaging/pathology
Aged, 80 and over
Middle Aged
Melanins

@article {pmid42029420,
year = {2026},
author = {James, TA and Zhao, L and Xu, H and Wu, J and Schweidel, DA and Goldstein, FC and Levey, AI and Qiu, D and Loring, DW and Hanfelt, JJ and Lah, JJ},
title = {Visual memory correlates with AD biomarkers in cognitively unimpaired individuals.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71417},
doi = {10.1002/alz.71417},
pmid = {42029420},
issn = {1552-5279},
support = {R01-AG070937/AG/NIA NIH HHS/United States ; IIS RD004723//Roche Diagnostics/ ; },
mesh = {Humans ; Male ; Female ; Biomarkers/cerebrospinal fluid ; Magnetic Resonance Imaging ; *Alzheimer Disease/cerebrospinal fluid ; Neuropsychological Tests ; Aged ; Middle Aged ; tau Proteins/cerebrospinal fluid ; *Memory/physiology ; Hippocampus/pathology/diagnostic imaging ; Adult ; Brain/diagnostic imaging/pathology ; Factor Analysis, Statistical ; },
abstract = {INTRODUCTION: Alzheimer's disease (AD) pathology evolves silently for many years prior to disease, and early identification of individuals at greatest risk is critical for improving outcomes.

METHODS: We conducted exploratory factor analysis (EFA) using neuropsychological testing of 1697 healthy adults. Factor scores were submitted as predictors for structural magnetic resonance imaging, functional connectivity, and cerebrospinal fluid (CSF) biomarkers.

RESULTS: The EFA model identified five latent factors. Factor 1, Verbal Memory, included high loadings from Rey Auditory Verbal Learning Test, and Factor 2, Visual Memory, included high loadings from Rey Complex Figure Test (RCFT). Factor 2 positively correlated with hippocampal volume, precuneus and posterior salience network connectivity, and negatively with CSF tau. Factor 1 correlated with hippocampal volume but not with network connectivity or CSF biomarkers.

DISCUSSION: Results demonstrate a significant relationship of visual memory with AD biomarkers. RCFT may be an important assessment for evaluating and tracking individuals during the earliest stages of AD pathology.},
}

Humans
Male
Female
Biomarkers/cerebrospinal fluid
Magnetic Resonance Imaging
*Alzheimer Disease/cerebrospinal fluid
Neuropsychological Tests
Aged
Middle Aged
tau Proteins/cerebrospinal fluid
*Memory/physiology
Hippocampus/pathology/diagnostic imaging
Adult
Brain/diagnostic imaging/pathology
Factor Analysis, Statistical

@article {pmid42029424,
year = {2026},
author = {Clark, AL and Hamlin, AM},
title = {Life course neighborhood conditions and change: a 20-year examination of neighborhood context and associations with Alzheimer's disease biomarkers in late life.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71382},
doi = {10.1002/alz.71382},
pmid = {42029424},
issn = {1552-5279},
support = {R03 AG085241/AG/NIA NIH HHS/United States ; P30AG066614//Center on Aging and Population Sciences at The University of Texas at Austin/ ; DGE-2137420//National Science Foundation Graduate Research Fellowship Program/ ; },
mesh = {Humans ; *Alzheimer Disease/blood/epidemiology ; Biomarkers/blood ; Male ; Female ; Aged ; Glial Fibrillary Acidic Protein/blood ; *Amyloid beta-Peptides/blood ; Neurofilament Proteins/blood ; Longitudinal Studies ; Middle Aged ; *Residence Characteristics ; *Neighborhood Characteristics/statistics & numerical data ; Aged, 80 and over ; Peptide Fragments/blood ; },
abstract = {INTRODUCTION: Life course models of Alzheimer's disease (AD) suggest that both long-term exposure to neighborhood conditions and changes in neighborhood context may shape dementia risk. This study examined the impact of mid- and late-life levels of neighborhood segregation, as well as longitudinal change in segregation, on plasma AD biomarkers.

METHODS: Participants were 119 racially/ethnically diverse (60% Black/Latino) adults. Residential addresses were geocoded to temporally harmonized US Census tracts, and the dissimilarity index quantified segregation. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aβ) 42/40 were measured.

RESULTS: Generalized estimating equations adjusting for individual-level sociodemographic and health characteristics revealed mid-life, but not late-life, levels of segregation were significantly associated with NfL. Increasing segregation across 10- and 20-year periods was associated with higher levels of GFAP and NfL, respectively.

DISCUSSION: Mid-life levels of segregation and longitudinal change in segregation were linked to plasma markers of neurodegeneration and astroglial activation.},
}

Humans
*Alzheimer Disease/blood/epidemiology
Biomarkers/blood
Male
Female
Aged
Glial Fibrillary Acidic Protein/blood
*Amyloid beta-Peptides/blood
Neurofilament Proteins/blood
Longitudinal Studies
Middle Aged
*Residence Characteristics
*Neighborhood Characteristics/statistics & numerical data
Aged, 80 and over
Peptide Fragments/blood

@article {pmid42029761,
year = {2026},
author = {Tekin, N and Şahin, F and Şahin, B and Kaya, ZZ and Yılmaz, A and Graham, SF and Serteser, M and Baykal, AT},
title = {A perspective for alzheimer disease from gut microbiota-associated NMR-based fecal metabolomics: a study with 5XFAD mice.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42029761},
issn = {1573-7365},
}

@article {pmid42029781,
year = {2026},
author = {Zhao, M and Abbasi, AA and Li, P and Lu, P},
title = {Mitochondrial dysfunction in sleep deprivation.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {42029781},
issn = {1573-7365},
support = {202401-06//Joint Innovation Team for Clinical & Basic Research/ ; 092-200012 PL//the Academic Promotion Program of Shandong First Medical University/ ; },
}

@article {pmid42029826,
year = {2026},
author = {Kwon, G and Kim, H and Kim, H and Lee, J},
title = {Generative Synthesis of Fractional Anisotropy Maps from T1 MRI Using Transfer Learning for White Matter Assessment in Stroke.},
journal = {Brain topography},
volume = {39},
number = {3},
pages = {},
pmid = {42029826},
issn = {1573-6792},
support = {RS-2023-00265824//Ministry of Science and ICT, South Korea/ ; RS-2026-25483830//National Research Foundation of Korea/ ; },
mesh = {Humans ; *White Matter/diagnostic imaging/pathology ; Male ; Female ; Aged ; Anisotropy ; Diffusion Tensor Imaging/methods ; *Magnetic Resonance Imaging/methods ; Middle Aged ; *Stroke/diagnostic imaging ; *Brain/diagnostic imaging ; Aged, 80 and over ; Neuroimaging/methods ; },
abstract = {Assessment of white matter integrity is critical for predicting functional recovery after ischemic stroke. However, conventional magnetic resonance imaging (MRI) cannot capture tract-specific microstructural changes, and diffusion tensor imaging (DTI) is limited by prolonged acquisition times. This study aimed to synthesize fractional anisotropy (FA) maps from routinely acquired T1-weighted (T1) MRI using 2.5D inputs within a generative adversarial network (GAN) framework. Specifically, our primary objective was to evaluate the relative efficacy of a proposed transfer learning strategy compared to single-domain training approaches. T1-FA paired data from 375 cognitively normal participants (832 images) from the Alzheimer's Disease Neuroimaging Initiative served as the non-lesion dataset, while longitudinal MRI data from 69 ischemic stroke patients (236 images) were from a single-center cohort. Three models were evaluated: the non-lesion-trained (NLT) model trained on non-lesion data, the lesion-trained (LT) model trained on stroke data, and the NLT model further fine-tuned on the stroke dataset (NLT + LF). Model performance was evaluated using voxel-wise errors (mean absolute error (MAE) and root mean square error (RMSE)), structural similarity (peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM)), spatial overlap (Dice coefficient (Dice)), and distributional similarity (Kullback-Leibler divergence). Bonferroni-corrected paired t-tests showed that NLT + LF showed significantly better performance than NLT across all evaluated regions, including the whole brain, white matter, and lesions (all p < 0.001). Compared with LT, NLT + LF showed superior performance for all metrics at p < 0.001, except for lesion-region Dice and RMSE, which remained significant at p < 0.01. The preservation of lesion-relevant features and anatomical fidelity, together with the capture of degeneration patterns, accompanied these gains. Overall, the proposed NLT + LF approach improved lesion-specific representation and established that high-fidelity FA maps can be reliably synthesized from T1 MRI. This transfer learning framework offers a practical alternative to DTI for clinical stroke assessment.},
}

Humans
*White Matter/diagnostic imaging/pathology
Male
Female
Aged
Anisotropy
Diffusion Tensor Imaging/methods
*Magnetic Resonance Imaging/methods
Middle Aged
*Stroke/diagnostic imaging
*Brain/diagnostic imaging
Aged, 80 and over
Neuroimaging/methods

@article {pmid42029989,
year = {2026},
author = {Sariaslani, A and Abrishami Moghaddam, H and A Ardekani, B and , },
title = {Corpus Callosum Segmentation on Structural MRI Using Multi-atlas Deformable Registration.},
journal = {Neuroinformatics},
volume = {24},
number = {2},
pages = {},
pmid = {42029989},
issn = {1559-0089},
}

@article {pmid42030001,
year = {2026},
author = {von Wegner, F and Hermann, G and Tödt, I and Todtenhaupt, IK and Laufs, H},
title = {A Quantitative Comparison of Two Methods for Higher-Order EEG Microstate Syntax Analysis.},
journal = {Brain topography},
volume = {39},
number = {3},
pages = {},
pmid = {42030001},
issn = {1573-6792},
mesh = {Humans ; *Electroencephalography/methods ; Entropy ; *Alzheimer Disease/physiopathology ; *Brain/physiopathology ; Markov Chains ; Male ; Female ; Aged ; Signal Processing, Computer-Assisted ; },
abstract = {Entropy rate (ER) and sample entropy (SE) are two metrics that have been used to quantify the syntactic complexity of electroencephalography (EEG) microstate sequences. We here present a theoretical and numerical comparison of these two metrics and apply them to a resting-state EEG dataset from individuals with Alzheimer's disease (AD) and a control group. We first derive theoretical ER and SE estimates for first-order discrete Markov processes, providing a null hypothesis for statistical testing of higher-order syntax properties. Under the first-order syntax null hypothesis, we find a close mathematical relationship between both metrics that can be expressed by the microstate transition probability matrix. An inequality is derived that shows ER to be an upper bound to SE under the Markov approximation. We quantify accuracy and precision of the theoretical ER and SE estimates on EEG microstate sequences from the healthy control group. We then show that ER and SE identify significant higher-order syntax properties in microstate sequences from the control and AD groups. We investigate continuous and jump microstate sequences. In the former, each time point is labelled with the best matching microstate label, and in the latter, duplicate labels are removed, exclusively retaining transitions between non-identical microstates. Group comparison demonstrates that continuous microstate sequences from the AD group have lower entropy values (ER, SE), whereas jump sequences from the AD group have higher entropy values compared to control. Finally, we introduce a new syntax metric that normalizes ER and SE values with respect to their first-order syntax levels, to assess differences that only depend on syntax order. This metric revealed no differences between control and AD groups for either continuous or jump microstate sequences. This study provides further insights into higher-order microstate syntax and how it can be quantified with respect to the underlying first-order syntax. Similarities and differences between ER and SE as syntax metrics are highlighted and exemplified on experimental data. Our results show that (i) EEG microstate sequences from control and AD subjects show higher-order syntax properties across the tested syntax levels, (ii) continuous and jump sequences from control and AD groups are syntactically different, and (iii) differences between the control and AD groups disappear when higher-order syntax properties are normalized to the group-specific Markov level.},
}

Humans
*Electroencephalography/methods
Entropy
*Alzheimer Disease/physiopathology
*Brain/physiopathology
Markov Chains
Male
Female
Aged
Signal Processing, Computer-Assisted

@article {pmid42030244,
year = {2026},
author = {do Carmo, JM and Hall, JE and Ladnier, E and Dai, X and Wang, Z and Mouton, AJ and Omoto, ACM and Jorge, L and da Silva, AA},
title = {Parental obesity exacerbates cognitive dysfunction and cardiac vulnerability in offspring of an Alzheimer disease model.},
journal = {American journal of physiology. Heart and circulatory physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpheart.00047.2026},
pmid = {42030244},
issn = {1522-1539},
support = {P30 GM149404/GM/NIGMS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; R01 DK121411/DK/NIDDK NIH HHS/United States ; R01 HL163076/HL/NHLBI NIH HHS/United States ; },
abstract = {Alzheimer disease (AD) is a growing health problem characterized by neurocognitive and cardiovascular dysfunction. Although parental obesity programs adverse cardiometabolic complications, including obesity, hypertension and cardiorenal dysfunction in their offspring, whether parental obesity worsens cardiac, metabolic, and cognitive function in lean offspring that are susceptible to AD (3xTg-AD mice) remains unclear. Male and female offspring from control diet-fed or high fat diet (HFD)-fed parents were examined at 26-28 weeks of age. Cognitive function was assessed by Morris Water Maze and New Object Recognition (NOR) tests, cardiac function by echocardiography and invasive hemodynamic measurements, and mitochondrial (MT) function by high-resolution respirometry in isolated cardiac fibers and brain cortex. AD offspring from obese parents (HFD-Offs) exhibited worse memory retention compared to AD offspring from lean parents (ND-Offs), whereas recognition memory assessed by NOR was not significantly different between groups although there was greater variability in HFD-Offs. Although systolic function by echocardiography was similar between groups, male HFD-Offs showed impaired diastolic relaxation with prolonged isovolumetric relaxation time (IVRT), while E/e' remained unchanged. Left ventricular catheterization showed reduced indices of contractility and relaxation, including maximal and minimal rates of pressure changes: dP/dtmax (8,038±1011 vs. 18,704±183 mmHg/sec), dP/dtmin (-7,724±471 vs. -13,634±1139) and prolonged Tau (4.0±0.1 vs. 2.9±0.1) in HFD-Offs compared to ND-Offs. Male HFD-Offs exhibited reduced MT glucose and fatty acid oxidation in heart and brain. These findings indicate that parental obesity exacerbates AD-related cognitive decline and cardiac dysfunction in a sex-specific manner, suggesting parental metabolic status as an important determinant of AD-related cardiometabolic vulnerability.},
}

@article {pmid42030370,
year = {2026},
author = {Panda, SR and Soni, U and Panja, P and Rajdev, B and Singh, M and Kundu, S and Ranade, A and Pawar, SD and Acharya, R and Naidu, VGM},
title = {Modulation of Mitochondrial Dynamics by Loganic Acid Ameliorates Alzheimer's Disease Pathology: Evidence from In Vitro and In Vivo Studies.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00012},
pmid = {42030370},
issn = {1948-7193},
abstract = {Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, which refers to forgetting facts and experiences. Apart from being a classical neuropathological hallmark, AD is connected with pronounced mitochondrial fragmentation, although the exact contribution of mitochondrial dynamics in AD progression is poorly defined. Therefore, this study is aimed at investigating the role of loganic acid (LGA) in mitochondrial dynamics, hippocampal plasticity, and cognitive deficits in the scopolamine (SC)-induced cognitive impairment model. The results showed significant decline of p-Drp1 protein and elevation of Mfn2 proteins in LGA-treated SC-induced mice, indicating reduced mitochondrial fragmentation and restoration of mitochondrial dynamics. In addition, LGA treatment promotes the reduction of fragmented and spherical-shaped mitochondria in SC-induced mice. LGA treatment alleviated reactive oxygen species (ROS) production and elevated mitochondrial membrane potential, reducing neurodegeneration in SC mice. Moreover, the decline of inflammatory cytokines (TNF-α and IL-1β) and downregulation of NF-kB expression in LGA-treated SC-induced mice suggested improved neuronal health. In parallel, LGA also increased the regulation of the cytoskeleton within neuronal dendrites, synaptic plasticity, and neuronal dendrites outgrowth, which was validated with increased expression of MAP2. In conclusion, the present study findings suggest that LGA exerts neuroprotection via preserving the mitochondrial ultrastructure and modulating the mitochondrial dynamics. All of these changes further restore neuronal cell density and myelination, leading to the mitigation of neurodegeneration, and restore cognitive deficits and spatial memory in SC-induced C57BL/6 mice.},
}

@article {pmid42030634,
year = {2026},
author = {Reyna-Sevilla, A and Rodríguez-Bolaños, R and Palacios-Rodríguez, OA and Gámez-Ortiz, R and Galarde-López, M and Ortega Ibarra, IH},
title = {Mental health conditions in Mexico: Diagnosis trends based on hospital records.},
journal = {Atencion primaria},
volume = {58},
number = {7},
pages = {103501},
doi = {10.1016/j.aprim.2026.103501},
pmid = {42030634},
issn = {1578-1275},
abstract = {OBJECTIVE: Analyze spatiotemporal trends in mental disorder diagnoses in Mexico between 2019 and 2023.

DESIGN: An ecological study was conducted based on records of mental disorder diagnoses in the population aged ≥21 years with social security coverage. SITE: Mexico, based on data from the National Open Data Platform on primary care units of the Mexican Social Security Institute (IMSS).

PARTICIPANTS: A total of 12,561,531 records obtained from diagnoses of mental disorders in the population aged ≥21 years with social security coverage during the period 2019-2023.

INTERVENTIONS: Rates were estimated, adjusted for sex and age. Spatio-temporal trends were evaluated using Moran's I index.

MAIN MEASURES: Classification of mental disorder, sex, age, entity, year.

RESULTS: At the national level, the mental disorder rate rose from 2419 per 100,000 population in 2019 to 7192 in 2023. Anxiety and obsessive-compulsive disorders, substance use disorders, and depressive episodes were the main diagnosis in both sexes. The data show a growing trend in mental disorders of various etiologies, in addition to depression and anxiety, which are treated by healthcare services. These disorders exhibited regional and gender-based variations during the study period.

CONCLUSIONS: It is recommended to expand health service coverage to strengthen the detection and diagnosis of mental disorder, reinforce primary care in regions at greatest risk, and incorporate prevention strategies for disorders that may increase in magnitude (dementias, Alzheimer's disease, schizophrenia, and delusional disorders).},
}

@article {pmid42030894,
year = {2026},
author = {Facci, L and Chemello, C and Marcolin, E and Franceschini, D and Scarin, N and Pagetta, A and Giusti, P and Moro, S and Zusso, M},
title = {Serum amyloid A1 directly engages TLR4/MD-2 to trigger neuroinflammatory signaling in microglia cultures.},
journal = {International immunopharmacology},
volume = {180},
number = {},
pages = {116710},
doi = {10.1016/j.intimp.2026.116710},
pmid = {42030894},
issn = {1878-1705},
abstract = {INTRODUCTION: Serum amyloid A1 (SAA1) is an inducible acute-phase protein produced in the liver and released in response to environmental and inflammatory stimuli, making it a reliable clinical biomarker of acute inflammation. In addition to its hepatic origin, SAA1 has been detected in axonal myelin sheaths in multiple sclerosis and Alzheimer's disease, suggesting that it may influence cells of the central nervous system (CNS) through several receptors, including Toll like receptors (TLRs).

AIM: We aimed to clarify the role of TLR4 in mediating SAA1-induced inflammation in CNS cells and to elucidate the molecular mechanisms of SAA1 interaction with the TLR4/MD-2 complex.

METHODS: We used an engineered TLR4 reporter cell system to assess TLR4 activation by SAA1. In primary microglia cultures, we evaluated the effects of SAA1 on pro-inflammatory mediators, with or without pharmacological inhibitors, including the TLR4 inhibitor CLI-095, curcumin, and L48H37. Biochemical and computational approaches were used to investigate direct interactions between SAA1 and the TLR4/MD-2 complex.

RESULTS: SAA1 activates the TLR4/MD-2 complex in a concentration-dependent manner. This effect was abolished by the TLR4 inhibitor CLI-095. Curcumin and L48H37, which bind to the hydrophobic pocket of MD-2, reduced SAA1-induced release of interleukin-1β, tumor necrosis factor-α, and nitric oxide, as well as NF-κB activation in microglia. Biochemical and computational studies confirmed a direct interaction between SAA1 and TLR4/MD-2.

CONCLUSIONS: SAA1 directly engages TLR4/MD-2 to trigger neuroinflammatory responses. Targeting this axis may attenuate SAA1-driven neuroinflammation and offers potential therapeutic strategies for neurodegenerative disorders.},
}

@article {pmid42030932,
year = {2026},
author = {Carnevale, LN and Banerjee, P and Zhang, X and Navarro, J and Raspur, CK and Patel, P and Nakamura, T and Schahrer, E and Scott, H and Lang, N and Diedrich, JK and Roberts, AJ and Yates, JR and Lipton, SA},
title = {Redox regulation of neuroinflammatory pathways contributes to damage in Alzheimer's disease brain.},
journal = {Cell chemical biology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.chembiol.2026.03.017},
pmid = {42030932},
issn = {2451-9448},
abstract = {Aberrant activation of innate immune signaling is known to contribute to neuroinflammation in age-related neurological disorders, but the mechanisms underlying this activation remain unclear. Here, we discovered that protein S-nitrosylation, a redox-based posttranslational modification, regulates the stimulator of interferon genes (STING) protein in Alzheimer's disease (AD). Using a combination of redox chemical biology and mass spectrometry, we identified S-nitrosylation at cysteine 148 as a critical modification facilitating STING oligomerization and triggering excessive type I interferon signaling in a causal fashion. This modification was observed in human AD postmortem brain tissue, in human induced pluripotent stem cell (hiPSC)-derived innate immune cells exposed to AD-related protein aggregates, and in a transgenic AD mouse model. Our findings reveal a novel molecular link between nitrosative stress and dysregulated innate immunity that drives neuroinflammation and synaptic loss in AD. Targeting this redox-sensitive cysteine presents a promising therapeutic strategy to modulate neuroinflammation and potentially slow disease progression.},
}

@article {pmid42030987,
year = {2026},
author = {Li, X and Zhang, C and Ni, H and Sun, P and Ren, J and Huang, S},
title = {MMP9 as a shared immune-related gene in Alzheimer's and Huntington's diseases: a cross-tissue transcriptomic analysis.},
journal = {Artificial cells, nanomedicine, and biotechnology},
volume = {54},
number = {1},
pages = {316-331},
doi = {10.1080/21691401.2026.2644164},
pmid = {42030987},
issn = {2169-141X},
mesh = {Humans ; *Huntington Disease/genetics/immunology ; *Matrix Metalloproteinase 9/genetics/immunology ; *Alzheimer Disease/genetics/immunology ; *Gene Expression Profiling ; Male ; *Transcriptome ; Organ Specificity/genetics ; Female ; Aged ; },
abstract = {Alzheimer's disease (AD) and Huntington's disease (HD) share neuroinflammatory mechanisms, yet their specific immune microenvironments remain poorly understood. Integrating transcriptomic profiles of peripheral blood and frontal cortex tissues with 2,160 immune-related genes, we analysed their shared immunopathology. Differential analysis identified 64 peripheral and 159 central consistently dysregulated immune genes, intersecting to isolate 10 co-expressed all-immune genes. Functional enrichment highlighted neutrophil and monocyte activation, alongside IL-17 and T-cell receptor signalling pathways. Machine learning (LASSO and Boruta) robustly pinpointed MMP9 as the core shared immune hub gene. External validation revealed MMP9 exhibited modest diagnostic performance in peripheral blood (AD AUC = 0.616; HD AUC = 0.619) but stronger predictive accuracy in brain tissues (AD AUC = 0.825; HD AUC = 0.876). Furthermore, MMP9 expression positively correlated with neutrophil and M0 macrophage infiltration. While modest peripheral accuracy limits its standalone diagnostic utility, this cross-tissue analysis establishes MMP9 as a consistently upregulated candidate molecular indicator of shared neuroinflammation, offering a valuable target for future mechanistic research.},
}

Humans
*Huntington Disease/genetics/immunology
*Matrix Metalloproteinase 9/genetics/immunology
*Alzheimer Disease/genetics/immunology
*Gene Expression Profiling
Male
*Transcriptome
Organ Specificity/genetics
Female
Aged

@article {pmid42031063,
year = {2026},
author = {Shi, C and Jia, K and Guo, Y and Qian, S and Wang, B and Qiu, Y and Dan, L and Dang, Z and Xue, K and Gao, F and Zhao, L},
title = {Disulfidptosis in Neurodegenerative Diseases: From Redox Imbalance to Neuronal Dysfunction.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116242},
doi = {10.1016/j.bbr.2026.116242},
pmid = {42031063},
issn = {1872-7549},
abstract = {Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress and cytoskeletal collapse under conditions of impaired reducing capacity. Neurodegenerative diseases (NDs), including Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, are characterized by oxidative stress, mitochondrial dysfunction, metabolic impairment, protein aggregation, and cytoskeletal instability-features that may provide a permissive intracellular context for disulfidptosis. However, its occurrence and pathological relevance in these disorders remain incompletely understood. In this review, we examine the potential involvement of disulfidptosis in neurodegenerative diseases from a disease-centered perspective. We emphasize that current evidence is largely indirect and based on mechanistic overlap rather than direct experimental validation in neural systems. Accordingly, we distinguish between direct evidence, indirect mechanistic support, and pathophysiological plausibility. We further discuss cell-type-specific susceptibility across neurons and glial cells, analyze its relationship with other cell death pathways, and consider potential therapeutic implications. Overall, disulfidptosis is best regarded as a context-dependent and emerging mechanism that may contribute to neuronal vulnerability under specific metabolic and redox constraints. Clarifying its disease relevance will be essential for determining its significance in neurodegeneration and its potential as a therapeutic target.},
}

@article {pmid42031084,
year = {2026},
author = {Segura, AH and Illán, IÁ and de Inestrosa, JRP and Román, FS and Martínez Murcia, FJ and Levin, J and Górriz Sáez, JM and , },
title = {Robust validation of neuroimaging and clinical models via the SAR method: A case study based on the ADNI dataset.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {121917},
doi = {10.1016/j.neuroimage.2026.121917},
pmid = {42031084},
issn = {1095-9572},
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and substantial brain atrophy. Early and accurate prediction of disease progression and staging is crucial for timely intervention and effective treatment planning. Previous studies, including those based on artificial intelligence techniques, have employed neuroimaging, biomarkers and clinical data to model AD progression; however, many of these approaches rely on strong parametric assumptions or lack robust statistical guarantees regarding model validity. To bridge this gap, this study proposes a novel framework for validating predictive and staging models of disease using a statistically agnostic methodology. The objective is to take the advantages of an unconventional method for robust validation of ML models related to AD. Validation is performed using the Statistical Agnostic Regression (SAR) methodology applied to the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. The method tests for a linear relationship by resampling and estimating an upper bound on the expected risk (R) via a Bayesian bound under the worst-case scenario. The SAR power assesses the likelihood of detecting a true linear relationship using the test statistic R, via Monte Carlo simulations under the null distribution. Three predictive models related to structural neuroimaging are assessed: one for the Mini Mental State Examination (MMSE) score, another for the concentration of amyloid beta 1-42 protein in the cerebrospinal fluid, and a third for age. In addition, a model for staging based on Alzheimer's-related clinical groups is explored through the joint analysis of segmented gray matter and white matter images. The findings indicate that the SAR methodology not only facilitates robust validation of predictive ML models related to neuroimaging and AD but also enables an effective staging of the AD continuum. This SAR-proposed framework opens new perspectives for the validation of ML models for early diagnosis and provides a solid foundation for future research in computational neuroscience.},
}

@article {pmid42031119,
year = {2026},
author = {Ferré-González, L and Peña-Bautista, C and López-Nogueroles, M and Durand, T and Baquero, M and Cháfer-Pericás, C},
title = {Sex-Specific lipid peroxidation profile and clinical features in a cognitive impairment cohort.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.04.143},
pmid = {42031119},
issn = {1873-4596},
abstract = {BACKGROUND: Alzheimer's disease (AD) displays a sex imbalance; women represent two-thirds of cases and often progress faster. Lipid peroxidation contributes to AD neurotoxicity from the oxidation of fatty acids can. However, how sex modulates plasma lipid peroxidation across clinical stages remains poorly characterized. This study examines sex- and AD clinical stage-related patterns in these plasma compounds.

METHODS: Plasma lipid peroxidation compounds were quantified by liquid chromatography/mass spectrometry in a clinical cohort stratified into 6 groups (cognitively unimpaired (without AD (n = 93), with AD (n=27)), mild cognitive impairment (due to AD (n = 105), not due to AD (n = 45)), mild dementia (due to AD (n = 84), not due to AD (n = 34))).

RESULTS: Across clinical groups, women showed a more severe clinical profile, while men showed higher neurofilament light chain (NfL) levels in several groups. Specifically, 10 lipid peroxidation compounds showed impaired levels in women with AD, while only 2 compounds in men. Notably, significant positive correlations were observed between certain lipid peroxidation compounds and cerebrospinal fluid (CSF) biomarkers exclusively in women. Positive correlations were observed between isoprostanes / neuroprostanes and some neuropyschological tests (CDR, MMSE, ADCS-ADL-MCI) in women, as well as mixed correlations between lipid peroxidation compounds and two tests (RBANS, FAQ) in men. Furthermore, multivariate analysis confirmed that clinical diagnosis was the main determining factor rather than biological sex, with 4 lipid peroxidation compounds (10-epi-10-F4t-NeuroP, 17-epi-17-F2t-dihomo-IsoP, total IsoP and total NeuroP) showing differences among clinical groups with distinct patterns of progression, specifically men showing higher levels in preclinical stages, while women showed more complex fluctuations throughout AD progression.

CONCLUSIONS: Plasma lipid peroxidation follows sex-dependent biological patterns across clinical stages of AD, highlighting a wider variety of altered biomarkers in women, which underscores the need to evaluate sex-stratified approaches for the diagnosis and AD staging.},
}

@article {pmid42031321,
year = {2026},
author = {Basha, S and Nadkarni, PP and Pai, AR and Mahato, KK},
title = {Co-Aggregation of Amyloidogenic Proteins in Age-Related Neurodegenerative Diseases.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103148},
doi = {10.1016/j.arr.2026.103148},
pmid = {42031321},
issn = {1872-9649},
abstract = {Age-related neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and related dementias, are increasingly understood as multifactorial proteinopathies involving co-aggregation of amyloidogenic proteins such as Tubulin-associated unit protein (Tau), α-synuclein (α-syn), amyloid-β (Aβ), and TAR DNA-binding protein 43 (TDP-43). Rather than acting independently, these proteins often cross-seed, co-localize, and modulate each other's aggregation dynamics and toxicity. This review critically examines the mechanistic and pathological underpinnings of heterotypic protein co-aggregation, integrating biophysical, cellular, animal, and human data. Further, this review proposes a conceptual framework that views neurodegeneration as a network of interacting misfolded proteins shaped by ageing-related changes in lipid membranes, redox balance, proteostasis, and genetic factors. Emphasis is placed on translational opportunities: co-aggregation-specific biomarkers in cerebrospinal fluid and extracellular vesicles, and emerging multi-targeted therapies including immunotherapy, proteostasis modulators, and autophagy-inducing chimeras. This review also discusses the clinical implications of co-pathology in mixed dementias and overlapping disorders. It is therefore time to move beyond the classical one protein-one disease paradigm and embrace models that explicitly incorporate heterotypic co-aggregation, mixed pathologies, and shared vulnerability pathways across ageing-related disorders. By reframing co-aggregation as a central pathogenic mechanism, this review highlights the need for diagnostics and therapeutics that address the interconnectivity of protein misfolding in ageing brains.},
}

@article {pmid42031360,
year = {2026},
author = {Li, X and Li, J and Sun, Y and Yao, T and Lu, Y and Liu, S and Li, H and Shi, Y and Chen, L and Zhao, Y and Jiang, W and Li, Z and Zhou, Z and Wang, B and Zhang, S and Yu, H and Lai, Y and Lu, Q and Li, Y and Li, H and Xu, Z and Wang, G and Zhu, Z},
title = {Challenges and delivery strategies for PROTACs in central nervous system therapeutics.},
journal = {Advanced drug delivery reviews},
volume = {},
number = {},
pages = {115876},
doi = {10.1016/j.addr.2026.115876},
pmid = {42031360},
issn = {1872-8294},
abstract = {The drug development for central nervous system (CNS) disorders, particularly neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, faces formidable challenges. While proteolysis-targeting chimeras (PROTACs) represent a paradigm-shifting modality by redefining target engagement mechanisms, their clinical translation remains hindered by limited blood-brain barrier (BBB) permeability and suboptimal pharmacokinetic profiles. In recent years, diverse CNS-targeted delivery strategies have emerged, driving PROTAC research toward translatable therapeutic potential. This Review highlights recent advances and persistent challenges in noninvasive BBB-penetrant delivery systems, including viral vectors, engineered exosomes, functionalized nanocarriers, and cell membrane-derived biomimetic vehicles, with a particular emphasis on intranasal administration as a direct route to the brain. Parallel progress in rational molecular engineering, encompassing E3 ligase selection, linker polarity and rigidity modulation, and optimization of target-binding ligands, has further enhanced PROTAC drug-likeness and BBB transport efficiency. Current CNS-directed PROTAC designs increasingly incorporate cell-penetrating peptides, nanoparticles, and prodrug formulations to balance stability, selectivity, and brain exposure. Future advanced PROTAC delivery platforms require integrating multifunctional nanocarriers with rational structural optimization to enhance BBB permeability. Further artificial intelligence-accelerated molecular design and targeted protein degradation technologies offer novel avenues for addressing undruggable CNS targets.},
}

@article {pmid42031363,
year = {2026},
author = {Gerwert, G and Mann, M and Langenhoff, L and Woitzik, N and Hubert, D and Duman, D and Höveler, A and Budde, S and Simon, J and Beyer, L and Schuler, M and Weber, S and Mollenhauer, B and Kötting, C and Güldenhaupt, J and Gerwert, K},
title = {An Immuno-Infrared Sensor Detects Preclinical Alzheimer's and Parkinson's Disease by Protein Misfolding.},
journal = {The journal of physical chemistry. B},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jpcb.6c00433},
pmid = {42031363},
issn = {1520-5207},
abstract = {The immuno-infrared sensor (iRS) detects misfolding of biomarker proteins in blood and provides thereby a very early and easily accessible diagnosis of Alzheimer's and Parkinson's disease. Only in early stages recently approved therapeutic Alzheimer's drugs work efficiently. In symptom-free stages, lifestyle change can largely delay the disease progression, and the drugs may even block the disease progression. Population screening by a simple blood test will therefore be a game changer in the fight against neurodegenerative diseases. This was made possible by the new iRS platform. In the iRS platform, antibodies as catcher molecules concentrate the target protein biomarker on the functionalized attenuated total reflection crystal surface. A blocking layer prevents unspecific binding. A quantum cascade laser is used to measure the amide I absorbance maximum as a readout, indicating the degree of the biomarker misfolding and thereby disease progression.},
}

@article {pmid42031657,
year = {2026},
author = {Kaur, A and Singh, S and Singh, M and Silakari, P and Mannan, A and Vishwas, S and Kumar, P and Subramaniyan, V and Singh, TG},
title = {Corrigendum to "Demethyleneberberine attenuates combined cognitive and metabolic dysfunctions in an insulin-resistance-induced Alzheimer's disease rat model: Synthesis, in-silico and in-vivo insights" [Experimental Neurology, 398 (2026) 115634].},
journal = {Experimental neurology},
volume = {},
number = {},
pages = {115774},
doi = {10.1016/j.expneurol.2026.115774},
pmid = {42031657},
issn = {1090-2430},
}

@article {pmid42031881,
year = {2026},
author = {Asiry, O and El-Gawady, A and Eltoukhy, MM and Mohamed, MF},
title = {LASSO-HHO two-stage hybrid gene selection framework for accurate Alzheimer's disease diagnosis.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42031881},
issn = {2045-2322},
support = {UJ-23-AKSPE-14//University of Jeddah/ ; },
mesh = {*Alzheimer Disease/diagnosis/genetics ; Humans ; Algorithms ; Gene Expression Profiling/methods ; *Computational Biology/methods ; Databases, Genetic ; },
abstract = {Selecting informative genes is essential for building accurate and efficient diagnostic models, especially for high-dimensional gene expression data such as those related to Alzheimer's disease. These datasets typically involve thousands of genes with limited samples, increasing the risk of overfitting and computational complexity. To address this, we propose a LASSO-HHO Gene Selection (LHGS) framework. LASSO is first applied to reduce dimensionality by filtering irrelevant genes. A conditional HHO-based optimization stage is then applied only when the LASSO-selected subset does not achieve sufficient accuracy or remains relatively large. Otherwise, the LASSO-selected features are directly used without further optimization. Experimental results show that the proposed method reduces the number of selected genes by up to 99.9% while maintaining high performance. The experimental results indicate that 100% accuracy can be achieved on specific datasets. In particular, GSE48350 and GSE36980 achieved 100% accuracy using LASSO alone, whereas GSE118553 and GSE132903 required the full LHGS framework to achieve the same performance. The framework also improves computational efficiency within a consistent experimental setup by reducing the optimization search space after LASSO filtering. Overall, LHGS provides a practical and efficient solution for gene selection in high-dimensional biomedical data.},
}

*Alzheimer Disease/diagnosis/genetics
Humans
Algorithms
Gene Expression Profiling/methods
*Computational Biology/methods
Databases, Genetic

@article {pmid42032039,
year = {2026},
author = {Dong, Y and Xiao, X and Zhuang, XX and Wu, W and Wang, ZY and Zhang, S and Li, JT and Zhang, K and Fu, WY and Chen, JM and Xiong, SH and Deng, S and Li, K and Ma, C and Jin, W and Jin, X and Cai, Q and Shen, HM and Li, M and Su, H and Wan, JB and Yu, H and Ouyang, D and Ye, K and Fang, EF and Tan, CSH and Yang, G and Niu, Z and Lu, JH},
title = {DeepDrugDiscovery identifies blood-brain barrier permeable autophagy enhancers for Alzheimer's disease.},
journal = {Nature biomedical engineering},
volume = {},
number = {},
pages = {},
pmid = {42032039},
issn = {2157-846X},
support = {0040/2024/RIB1//Fundo para o Desenvolvimento das Ciências e da Tecnologia (Science and Technology Development Fund)/ ; },
abstract = {Dysfunctional autophagy, a key cellular cleaning process, is a key driver of brain ageing and neurodegenerative diseases such as Alzheimer's disease (AD). However, developing effective treatments by enhancing autophagy has been challenging, as most known compounds act through the broad mTOR pathway, risking side effects, and few can effectively penetrate the brain. To address this, we developed DeepDrugDiscovery-a mechanism-aware, AI-powered screening platform incorporating ADMET and blood-brain barrier penetrability predictions. Here we show that this platform successfully identified novel, mTOR-independent autophagy enhancers, with two lead compounds demonstrating an ability to cross the blood-brain barrier, clear AD-related protein aggregates and restore memory function in worm and mouse AD models. By releasing DeepDrugDiscovery as an open-source, modular tool, we offer a user-friendly AI platform that enables customized therapeutic screening. Our work establishes a scalable, AI-driven pipeline that integrates cross-species validation to rapidly discover mechanism-based therapeutics for diseases with high unmet medical need.},
}

@article {pmid42032173,
year = {2024},
author = {Hasan, WU and Zaman, KT and Wang, X and Li, J and Xie, B and Tao, C},
title = {Empowering Alzheimer's caregivers with conversational AI: a novel approach for enhanced communication and personalized support.},
journal = {npj biomedical innovations},
volume = {1},
number = {1},
pages = {},
pmid = {42032173},
issn = {3005-1444},
support = {2218046//National Science Foundation/ ; 2218046//National Science Foundation/ ; 2218046//National Science Foundation/ ; 2218046//National Science Foundation/ ; 2218046//National Science Foundation/ ; 2218046//National Science Foundation/ ; },
abstract = {Alzheimer's disease and related dementias (ADRD) place a significant burden on caregivers. To address this, we developed ADQueryAid, a conversational AI system designed to empower ADRD caregivers. Built on a Large Language Model and enriched with ADRD knowledge, ADQueryAid uses Retrieval-Augmented Generation to provide personalized and informative support. A user study comparing ADQueryAid to a baseline model (ChatGPT 3.5) demonstrated its superior usability, offering contextually relevant information and emotional support. This study highlights the potential of tailored AI systems to enhance the caregiving experience, paving the way for future research on their long-term impact.},
}

@article {pmid41814062,
year = {2026},
author = {Margarian, S and Chen, Y and Waheed, J and Rezaeimanesh, P and Chiang, VS and Takehara-Nishiuchi, K},
title = {Cost-effective, open-source, automated apparatus for testing transitive inference in mice.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {41814062},
issn = {2045-2322},
abstract = {Transitive inference is a form of reasoning that relies on prior knowledge and benefits survival in diverse species. While initially designed for humans, the transitive inference task has been adapted for mice, allowing for integration with various state-of-the-art manipulation and monitoring tools for mechanistic investigations. Existing paradigms, however, rely on manually presented stimuli, making them time-consuming, labor-intensive, and error-prone. Here, we introduce AutoTI, a fully automated behavioral apparatus that precisely controls the timing of task events and logs timestamps for events and responses. The automation also enables continuous, undisturbed monitoring of spontaneous behavior, allowing for detailed analyses of movement trajectory beyond basic accuracy metrics. Using AutoTI, we developed a robust training protocol that reliably achieved high success rates on transitive tests in mice. Notably, mice exhibited hallmark behavioral patterns seen in humans, including the symbolic distance effect and the serial position effect. AutoTI provides a cost-effective and scalable system for investigating the neurobiological basis of inferential reasoning. It also holds promise for translational research targeting its impairment in autism, schizophrenia, and Alzheimer’s disease, as well as advancing the reasoning capabilities of artificial intelligence.},
}

@article {pmid42020180,
year = {2026},
author = {Tong, FF and Huang, RQ and Gao, Y and Luo, QQ and Chen, YP and Xu, GZ},
title = {[Epidemiological studies of the association between dyslipidemia and Alzheimer's disease].},
journal = {Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi},
volume = {47},
number = {4},
pages = {767-774},
doi = {10.3760/cma.j.cn112338-20250727-00528},
pmid = {42020180},
issn = {0254-6450},
mesh = {*Alzheimer Disease/epidemiology ; Humans ; *Dyslipidemias/epidemiology/complications ; Risk Factors ; },
abstract = {Alzheimer's disease (AD), as the representative type of dementia among neurodegenerative diseases, has become a major challenge in the field of global public health. Dyslipidemia is considered an acquired risk factor for AD, and both are progressive diseases with long developmental periods, making dyslipidemia a potential predictor of future AD occurrence. Therefore, preventing dyslipidemia is of great significance for the prevention and treatment of AD. Given the global epidemiological background of AD, this article aims to systematically review the association between dyslipidemia and AD, providing theoretical support for the prevention and control of both conditions.},
}

*Alzheimer Disease/epidemiology
Humans
*Dyslipidemias/epidemiology/complications
Risk Factors

@article {pmid42020356,
year = {2026},
author = {Zou, Z and Chen, J and Li, J and Chen, Y},
title = {The iron-energy metabolism axis in Alzheimer's pathogenesis: from mechanisms to interventions.},
journal = {Cell death discovery},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41420-026-03034-w},
pmid = {42020356},
issn = {2058-7716},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder with a complex, multifactorial pathogenesis. Growing evidence implicates disturbances in cellular energy metabolism and iron dyshomeostasis as interlinked contributors to pathology. Within this framework, iron accumulation may act as an upstream regulator in certain contexts and stages, while in others it emerges downstream and amplifies ongoing injury. As iron is an essential cofactor for mitochondrial respiration and the tricarboxylic acid cycle, iron imbalance can compromise ATP production and disrupt glucose metabolism, exacerbating neuronal energy deficits. The interplay among iron accumulation, oxidative stress, and neuroinflammation can create vicious cycles that reprogram cellular metabolism and disrupt the critical metabolic coupling between neurons and glial cells. This review synthesizes recent advances in understanding the iron-energy metabolism axis in AD, delineates mechanisms by which iron imbalance precipitates mitochondrial dysfunction and glucose metabolic impairments, and evaluates how these deficits synergize with neuroinflammation and proteinopathy across disease stages. Finally, we appraise emerging therapeutic strategies targeting iron overload and metabolic pathways, discuss their stage-dependent risks and benefits, and outline the need for biomarker-guided approaches to optimize patient selection and treatment timing.},
}

@article {pmid42020486,
year = {2026},
author = {Ahn, JW and Yoon, EJ and Kim, HS and Choi, Y and Jeong, J and Damodar, K and Yoo, YM and Park, D and Joo, SS},
title = {HSN G1 demonstrates multifaceted therapeutic strategy against Alzheimer disease in APP PS1 mouse model.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-49541-9},
pmid = {42020486},
issn = {2045-2322},
abstract = {Current therapeutic approaches for Alzheimer's disease (AD) demonstrate limited efficacy and fail to address disease progression. In the present study, we present HSN-G1, a novel ginsenoside-enriched pharmaceutical formulation that employs a dual-target mechanism through the modulation of amyloid clearance pathways and cholinergic neurotransmission. HSN-G1 demonstrates a reproducible ginsenoside profile enriched with Re (33.27 mg/g), Rd (25.00 mg/g), and Rg3 stereoisomers (12.18 mg/g), ensuring pharmaceutical-grade reproducibility. HSN-G1 enhanced amyloid-beta (Aβ) clearance in microglial cells, with significantly greater effects observed in SRA-overexpressing cells, suggesting SRA-dependent clearance mechanisms. In APP/PS1 transgenic mice, six-week oral administration of HSN-G1 (100-400 mg/kg) elicited significant dose-dependent improvements in cognitive performance. Male mice exhibited more stable and consistent enhancements in both passive avoidance and spatial memory tests compared to vehicle controls (p < 0.001), while both sexes demonstrated comparable reductions in brain Aβ levels (approximately 45%) and differential increases in acetylcholine (73% in males; 55% in females, p < 0.01). HSN-G1 administration enhanced the expression of neurotrophic factors, with NGF upregulation predominantly observed in males, whereas BDNF, CNTF, and GDNF were consistently elevated across both sexes. These findings establish HSN-G1 as a promising disease-modifying agent with standardized composition and therapeutic efficacy, surpassing the limitations of conventional single-target approaches. The superior efficacy of HSN-G1 compared to existing treatments validates its potential for clinical development, highlighting the significance of sex-specific therapeutic responses in future AD therapeutics.},
}

@article {pmid42020643,
year = {2026},
author = {Liu, G and Xie, B and Zhao, J and Lv, L},
title = {LINC00926 promotes microglial M1 polarization and neuroinflammation by sponging miR-383-3p in Alzheimer's disease: a potential diagnostic and therapeutic target.},
journal = {Acta neurologica Belgica},
volume = {},
number = {},
pages = {},
pmid = {42020643},
issn = {2240-2993},
}

@article {pmid42020711,
year = {2026},
author = {Liu, Q and Parrish, RL and Tang, S and Tasaki, S and Bennett, DA and Seyfried, NT and De Jager, PL and Menon, V and Buchman, AS and Yang, J},
title = {Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10030-4},
pmid = {42020711},
issn = {2399-3642},
support = {R35GM138313//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; R01AG089703//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {Most existing transcriptome wide association studies (TWASs) of Alzheimer's Disease (AD) dementia only use bulk RNA-seq data and a single statistical method. Here, we utilize an omnibus TWAS (TWAS-O) pipeline that leverages multiple complementary statistical methods to integrate the snRNA-seq dataset (n = 415) of the dorsolateral prefrontal cortex (DLPFC) and the latest GWAS data of AD dementia. We fine-map TWAS risk genes by gene-based conditional analysis and conducted validation analyses by the analogous omnibus proteome-wide association studies (PWAS-O) using bulk proteomics data of DLPFC (n = 716). We identify 223 unique cell-type-aware TWAS risk genes from 350 associations across six major brain cell-types, including 91 fine-mapped independent associations, 11 of which are novel. By PWAS-O, we identify 21 significant PWAS risk genes, including 13 independent associations, which validated 31.9% independent cell-type-aware TWAS associations. By protein-protein interaction network analyses, our novel cell-type-aware TWAS findings are linked to established AD risk genes such as APOE, BIN1, and MAPT.},
}