@article {pmid41943055,
year = {2026},
author = {Di Caro, V and Cho, E and Thiel, J and Lizama, BN and Koel-Simmelink, MJA and Pandey, K and Duong, D and Seyfried, NT and Grundman, M and Teunissen, CE and Zetterberg, H and Blennow, K and Caggiano, AO and Hamby, ME},
title = {Impact of zervimesine on the neuroinflammatory biomarker GFAP and related proteomic molecular correlates in plasma of participants from a phase 2 clinical trial in Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02025-4},
pmid = {41943055},
issn = {1758-9193},
support = {1R01AG058660/AG/NIA NIH HHS/United States ; 1R01AG058660/AG/NIA NIH HHS/United States ; 1R01AG058660/AG/NIA NIH HHS/United States ; 1R01AG058660/AG/NIA NIH HHS/United States ; 1R01AG058660/AG/NIA NIH HHS/United States ; 1R01AG058660/AG/NIA NIH HHS/United States ; },
}

@article {pmid41943113,
year = {2026},
author = {Spruyt, L and Mlinarič, T and Dusart, N and Reinartz, M and Van Hulle, MM and Sunaert, S and Van Laere, K and Dupont, P and Vandenberghe, R},
title = {The electrophysiological basis of resting-state fMRI hyperconnectivity in early Alzheimer's disease.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02003-w},
pmid = {41943113},
issn = {1758-9193},
support = {G094418N//Fonds Wetenschappelijk Onderzoek/ ; C14/21/109//KU Leuven Bijzonder Onderzoeksfonds/ ; HBC.2019.2523//Vlaams Agentschap voor Innovatie en Onderzoek/ ; 2022/0009//Stichting Alzheimer Onderzoek/ ; },
}

@article {pmid41943176,
year = {2026},
author = {Park, CH and Shin, D and Chung, KC},
title = {DAPK1-Mediated Parkin Inactivation Enhances Neurotoxicity via MITOL-Dependent Degradation.},
journal = {Journal of cellular and molecular medicine},
volume = {30},
number = {7},
pages = {e71132},
doi = {10.1111/jcmm.71132},
pmid = {41943176},
issn = {1582-4934},
support = {RS-2024-00450988//National Research Foundation of Korea/ ; },
mesh = {*Ubiquitin-Protein Ligases/metabolism/genetics ; *Death-Associated Protein Kinases/metabolism/genetics ; Humans ; *Mitochondria/metabolism ; Phosphorylation ; Proteolysis ; Animals ; Parkinson Disease/metabolism/pathology/genetics ; alpha-Synuclein/metabolism ; *Mitochondrial Proteins/metabolism ; Neurons/metabolism ; Oxidopamine/toxicity ; },
abstract = {Parkinson's disease (PD) is characterised by progressive neurodegeneration and is marked by the formation of Lewy bodies, which are intracellular aggregates primarily composed of α-synuclein. Mitochondrial dysfunction and impaired protein degradation pathways are thought to play critical roles in PD progression, contributing to the loss of dopaminergic neurons in the substantia nigra. Phosphorylation of α-synuclein has been shown to promote its aggregation, underscoring its potential role in disease progression. Parkin, an E3 ubiquitin ligase, is widely regarded as a pleiotropic neuroprotective protein that modulates the mitochondrial quality control, as well as metabolic turnover and the accumulation of α-synuclein. Death-associated protein kinase 1 (DAPK1), which is involved in the regulation of apoptosis and autophagy, has recently emerged as an important factor in neurodegeneration. While DAPK1 has been implicated in Alzheimer's disease through its role in tau aggregation and amyloid-β production, our findings suggest that DAPK1 may also influence PD-related pathways by phosphorylating parkin at Ser136 and Ser198. This phosphorylation promotes the mitochondrial transport of parkin, enhancing interaction with mitochondria-localised E3 ubiquitin ligase MITOL and consequently leading to the degradation of parkin. Given the neuroprotective role of parkin, its reduction increases the vulnerability of neurons to 6-hydroxydopamine-induced toxicity, potentially contributing to decreased neuronal survival. Together, these findings suggest that DAPK1 functions as a previously unrecognised modulator of parkin and could potentially influence PD-related neurodegenerative processes. This pathway may provide a mechanistic link between mitochondrial dysfunction, α-synuclein pathology and neuronal cell death.},
}

*Ubiquitin-Protein Ligases/metabolism/genetics
*Death-Associated Protein Kinases/metabolism/genetics
Humans
*Mitochondria/metabolism
Phosphorylation
Proteolysis
Animals
Parkinson Disease/metabolism/pathology/genetics
alpha-Synuclein/metabolism
*Mitochondrial Proteins/metabolism
Neurons/metabolism
Oxidopamine/toxicity

@article {pmid41943474,
year = {2026},
author = {Stahr, N and Moriarty, AK and Ma, SD and Keeter, WC and Kim, WK and Sanford, LD and Galkina, EV},
title = {STAT4-dependent regulation of neuroinflammation in atherosclerosis.},
journal = {Physiological reports},
volume = {14},
number = {7},
pages = {e70856},
doi = {10.14814/phy2.70856},
pmid = {41943474},
issn = {2051-817X},
support = {R01HL142129//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; R01HL139000//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL142129-04S1//HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; 20PRE35180156//American Heart Association (AHA)/ ; },
mesh = {Animals ; *STAT4 Transcription Factor/metabolism/genetics ; *Atherosclerosis/metabolism/pathology ; Mice ; *Neuroinflammatory Diseases/metabolism/pathology ; Mice, Knockout ; Microglia/metabolism ; Male ; Mice, Inbred C57BL ; Receptors, LDL/genetics ; Brain/metabolism/pathology ; Diet, High-Fat/adverse effects ; Macrophages/metabolism ; },
abstract = {Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM[Cre]-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr[-/-]) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune composition, characterized by increased numbers of CD45[+] leukocytes, activated microglia, and activated T and B cells, whereas STAT4 deficiency attenuates these effects. Nanostring gene-expression pathway analysis further highlights the importance of STAT4 in regulating multiple neuroinflammatory pathways and the Rhodopsin-like receptor signaling, which is associated with synaptic plasticity. LysM[Cre]-specific STAT4 deficiency supports microglial efferocytosis in atherosclerotic Ldlr[-/-] mice and increases the number of efferocytotic macrophages. Accordingly, STAT4 deficiency also reduces neuronal death. Overall, our data reveal an important role for myeloid-driven STAT4 expression in the pathogenesis of cognitive decline associated with atherosclerosis, mediated through impaired efferocytosis and enhanced leukocyte activation, leading to increased brain neuroinflammation.},
}

Animals
*STAT4 Transcription Factor/metabolism/genetics
*Atherosclerosis/metabolism/pathology
Mice
*Neuroinflammatory Diseases/metabolism/pathology
Mice, Knockout
Microglia/metabolism
Male
Mice, Inbred C57BL
Receptors, LDL/genetics
Brain/metabolism/pathology
Diet, High-Fat/adverse effects
Macrophages/metabolism

@article {pmid41943483,
year = {2026},
author = {Karabova, MK and Del Ser-Badia, A and Hedegaard, A and Washer, SJ and Baykam, Z and O'Brien, DP and Vendrell, I and Hester, SS and Fischer, R and Johnson, E and Melia, CE and Matthews-Palmer, TRS and Matadeen, R and Santambrogio, A and Metrick, MA and Vendruscolo, M and Keeling, S and Cheam, KAX and McEwan, WA and Kosik, KS and Day, TA and James, WS and Cowley, SA},
title = {Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71337},
doi = {10.1002/alz.71337},
pmid = {41943483},
issn = {1552-5279},
support = {//The James Martin 21st Century Research Foundation/ ; },
mesh = {Humans ; *Induced Pluripotent Stem Cells/metabolism ; *tau Proteins/metabolism ; *Microglia/metabolism ; *Extracellular Vesicles/metabolism ; Alzheimer Disease/metabolism/pathology ; Low Density Lipoprotein Receptor-Related Protein-1/metabolism ; Brain/metabolism ; },
abstract = {INTRODUCTION: Microglia have been implicated in the templated spread of tau aggregates in tauopathies through mouse studies. However, it is unclear whether these findings translate to human disease.

METHODS: We challenged human induced pluripotent stem cell (iPSC)-derived microglia-like-cells (iMGL) with monomeric and fibrillar recombinant tau and tau purified from Alzheimer's patient brains, examining in detail the uptake, processing, release, and seeding of tau by microglia.

RESULTS: iMGL take up tau via lipoprotein receptor-related protein 1 (LRP)1 and heparan sulfate proteoglycans, with leucine-rich repeat kinase 2 affecting LRP1 trafficking. Monomeric tau is digested effectively with minimal effects on iMGL, but recombinant or brain-derived tau fibrils induce chemokine/interferon response subtypes, alongside downregulation of homeostatic genes. Fibrillar tau is degradation-resistant, can escape into the cytoplasm, and becomes phosphorylated on two specific residues. iMGL release partially digested fibrillar tau, including in extracellular vesicles, visualized by cryo-electron microscopy, that seed aggregation in neurons.

DISCUSSION: Our study reveals new insights into human microglial responses to tau, highlighting opportunities to limit pathogenic tau spread.},
}

Humans
*Induced Pluripotent Stem Cells/metabolism
*tau Proteins/metabolism
*Microglia/metabolism
*Extracellular Vesicles/metabolism
Alzheimer Disease/metabolism/pathology
Low Density Lipoprotein Receptor-Related Protein-1/metabolism
Brain/metabolism

@article {pmid41943492,
year = {2026},
author = {Jung, DH and Park, E and Ju, HC and Moon, C and Jahanshahi, A},
title = {Glial pathology networks reveal early olfactory vulnerability in post mortem human Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71322},
doi = {10.1002/alz.71322},
pmid = {41943492},
issn = {1552-5279},
support = {RS-2020-NR049577//Ministry of Education/ ; RS-2023-00278057//Ministry of Science and ICT/ ; },
mesh = {Humans ; *Alzheimer Disease/pathology/metabolism ; Male ; *Olfactory Bulb/pathology/metabolism ; Female ; *Neuroglia/pathology/metabolism ; Aged ; *Olfactory Cortex/pathology/metabolism ; Amyloid beta-Peptides/metabolism ; Aged, 80 and over ; tau Proteins/metabolism ; Cognitive Dysfunction/pathology/metabolism ; Autopsy ; Apolipoproteins E/metabolism ; Microglia/pathology/metabolism ; Glial Fibrillary Acidic Protein/metabolism ; Astrocytes/pathology/metabolism ; },
abstract = {INTRODUCTION: The olfactory system is an early target in Alzheimer's disease (AD), yet regional glial pathology interactions remain poorly defined. We examined how glial activation and pathological burden differ between the olfactory cortex (OC) and olfactory bulb (OB) across disease stages.

METHODS: Post mortem OC and OB samples from cognitively normal (CN), mild cognitive impairment, and AD cases were analyzed using immunohistochemistry and immunofluorescence for amyloid beta (Aβ), phosphorylated tau (pTau), Iba1 (microglia), GFAP (astrocyte), and apolipoprotein E (apoE).

RESULTS: Both regions showed stage-dependent increases in Aβ and pTau, with regionally distinct glial responses. ApoE signal varied with clinical stage rather than genotype. Co-expression analyses revealed astrocyte-linked networks in the OC and microglia-linked relationships in the OB.

DISCUSSION: Findings demonstrate spatially heterogenous glial pathology architectures in the human olfactory system, supporting its role as an early and regionally diverse site of AD vulnerability.},
}

Humans
*Alzheimer Disease/pathology/metabolism
Male
*Olfactory Bulb/pathology/metabolism
Female
*Neuroglia/pathology/metabolism
Aged
*Olfactory Cortex/pathology/metabolism
Amyloid beta-Peptides/metabolism
Aged, 80 and over
tau Proteins/metabolism
Cognitive Dysfunction/pathology/metabolism
Autopsy
Apolipoproteins E/metabolism
Microglia/pathology/metabolism
Glial Fibrillary Acidic Protein/metabolism
Astrocytes/pathology/metabolism

@article {pmid41943532,
year = {2026},
author = {Acewicz, A and Tarka, S and Grzegorczyk, M and Rzepliński, R and Wierzba-Bobrowicz, T and Stępień, T},
title = {Associations between TMEM106B C-terminal fragment aggregation, age, and TDP-43 or tau pathology.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70090},
doi = {10.1111/bpa.70090},
pmid = {41943532},
issn = {1750-3639},
support = {//Institute of Psychiatry and Neurology, Warsaw, Poland/ ; },
abstract = {Transmembrane protein 106B (TMEM106B) is a lysosomal glycoprotein whose genetic polymorphisms contribute to the severity of neurodegenerative disorders associated with TDP-43 pathology. Recent studies have revealed that TMEM106B can form amyloid filaments composed of C-terminal fragments (CTFs) in the human brain. In the present study, we explored the relationships between TMEM106B, age, TDP-43, and tau aggregates, and their roles in neurodegeneration. We used immunohistochemistry with an antibody against CTFs of TMEM106B on postmortem human brain fragments (amygdala, hippocampus, temporal cortex, frontal cortex, and basal ganglia) from patients with and without TDP-43/tau pathology at different ages (6-94 years) and with different neurological conditions (subacute sclerosing panencephalitis, Alzheimer's disease, frontotemporal lobar degeneration, and neurologically healthy subjects). Our results revealed that TMEM106B CTF fibrillization is a common, nonspecific, diffuse, and age-dependent phenomenon (appearing after >52 years of age) that affects neurons and neuroglia (most numerous in astrocytes and oligodendrocytes) and broad neuroanatomical regions (most severe in the temporal cortex). We did not find TMEM106B CTF aggregates in young subjects with TDP-43/tau pathology (with subacute sclerosing panencephalitis), but we revealed differences in TMEM106B CTF fibrillization between Alzheimer's disease without TDP-43 pathology, frontotemporal lobar degeneration with TDP-43 pathology, and older healthy subjects without TDP-43/tau pathology. Our results suggest that TMEM106B CTF aggregation is an age-dependent phenomenon and may have a weak association with TDP-43 or tau pathology, shedding new light on the complex relationships among TMEM106B, TDP-43, and tau and the unclear role of TMEM106B fibril formation in the neurodegeneration process.},
}

@article {pmid41943538,
year = {2026},
author = {Marriott, AE and Schroeder, JP and Korukonda, A and Pate, BS and McCann, KE and Weinshenker, D and Kelberman, MA},
title = {Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71334},
doi = {10.1002/alz.71334},
pmid = {41943538},
issn = {1552-5279},
support = {AG062581/AG/NIA NIH HHS/United States ; AG069502/AG/NIA NIH HHS/United States ; AG066511/AG/NIA NIH HHS/United States ; NS96050//and National Institute of Neurological Disorders and Stroke/ ; },
mesh = {Animals ; *Alzheimer Disease/pathology ; *Locus Coeruleus/pathology/drug effects ; Disease Models, Animal ; Rats ; Rats, Transgenic ; Rats, Inbred F344 ; Male ; Plaque, Amyloid/pathology ; },
abstract = {INTRODUCTION: In murine models of Alzheimer's disease (AD), lesioning the locus coeruleus-norepinephrine (LC-NE) system with DSP-4 exacerbates AD-like neuropathology and cognitive impairment. However, the impact of LC lesions during prodromal stages is poorly characterized.

METHODS: TgF344-AD and wild-type rats received monthly injections of DSP-4 or saline from 1-5 months of age, a time point preceding forebrain plaque or tangle deposition in TgF344-AD rats, after which behavior and pathology were assessed.

RESULTS: DSP-4 compromised LC cell bodies, fibers, and NE content. LC lesion and the AD transgene each affected several affective behaviors and/or cognition individually, but few interactions were found, and DSP-4 failed to exacerbate behavioral phenotypes or neuropathology in TgF344-AD rats.

DISCUSSION: Combined with previous literature, our data suggest that LC lesions exacerbate pre-existing AD-like pathology and behavioral impairments, rather than accelerate their onset. Further characterization of LC lesions in TgF344-AD rats at different ages is warranted.},
}

Animals
*Alzheimer Disease/pathology
*Locus Coeruleus/pathology/drug effects
Disease Models, Animal
Rats
Rats, Transgenic
Rats, Inbred F344
Male
Plaque, Amyloid/pathology

@article {pmid41943580,
year = {2026},
author = {Ye, Y and Zhang, Z and Xiao, Y and Zhu, C and Wright, N and Asbury, J and Huang, Y and Wang, W and Gomez-Isaza, L and Troncoso, JC and He, C and Sun, S},
title = {DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.01.018},
pmid = {41943580},
issn = {1097-4199},
abstract = {The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping scavenger enzyme (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal that TDP-43 LOF leads to aberrant mRNA degradation via dysregulating the properties and activity of processing bodies (P-bodies). TDP-43 interacts with P-body component proteins, potentially influencing their dynamic equilibrium and assembly into ribonucleoprotein (RNP) granules. Loss of TDP-43 hyperactivates P-bodies, increasing mRNA association and RNA decay. Reducing DCPS restores P-body integrity and RNA turnover, ultimately improving neuronal survival. Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.},
}

@article {pmid41943747,
year = {2026},
author = {Bhatia, P and Rosales, JP and Patel, P and Brini, G and Singh, J and Patel, R and Petroski, J and Brisman, B and Sandhu, M and Santacroce, N and Singh, A and Kaur, G},
title = {The Crossroads of Neurodegeneration: Exploring the Overlap Between Alzheimer's Disease and Depression.},
journal = {Cureus},
volume = {18},
number = {3},
pages = {e104771},
pmid = {41943747},
issn = {2168-8184},
abstract = {Alzheimer's disease (AD) and depression are two prevalent and debilitating neuropsychiatric disorders that frequently occur together and share overlapping clinical and molecular features. Understanding shared features of AD and depression is critical for delaying disease progression and improving quality of life. The objective of this narrative review is to identify recent advances in the understanding of AD and its link to depression, with a focus on identifiable biomarkers. This review explores the converging pathophysiological pathways implicated in both AD and depression, with an emphasis on oxidative stress, mitochondrial dysfunction, microglial activation, vascular impairment, and metal ion dysregulation. Specific attention is given to biomarkers of lipid peroxidation, nucleic acid damage, and protein nitration, as well as to the role of telomerase activity and ferroptosis in neuronal cell death. Additionally, we evaluate the therapeutic potential of antidepressants in modifying disease trajectory and reducing depressive symptoms in AD patients. By investigating the molecular intersections of AD and depression, this review aims to provide a comprehensive understanding of their shared pathology and highlight new avenues for targeted interventions. Our review underscores the overlapping mechanisms between AD and depression, paving the way for earlier detection, targeted therapies, closer monitoring, and improved patient outcomes.},
}

@article {pmid41943971,
year = {2026},
author = {Aracki-Trenkic, A and Živanović, M and Milošević, V and Bašić, J and Radovanović, D and Malobabić, M},
title = {Structural MRI phenotyping in Alzheimer's disease: Comparison of visual rating scales, volumetry, and cortical thickness in a Serbian single-centre cohort.},
journal = {Biomolecules & biomedicine},
volume = {},
number = {},
pages = {},
doi = {10.17305/bb.2026.13974},
pmid = {41943971},
issn = {2831-090X},
abstract = {Alzheimer's disease (AD) is characterized by a heterogeneous clinical course, and magnetic resonance imaging (MRI)-based phenotyping has increasingly been utilized to elucidate this variability. The literature recognizes four predominant MRI phenotypes: typical, hippocampal-sparing, limbic-predominant, and minimal-atrophy. However, the compatibility of various MRI phenotyping methods remains insufficiently defined. This study aimed to assess the concordance between MRI phenotyping methods within a Serbian cohort consisting of 40 subjects. Four MRI phenotyping approaches were employed: scale-based, adjusted scale-based, volume-based, and thickness-based. The scale-based method exhibited moderate agreement with the adjusted scale-based approach and high concordance with volumetric methods. In contrast, the relationship between scale- and thickness-based phenotyping was less clear. The lack of significant agreement with demographic variables, along with the observed differences across clinical dementia rating (CDR) domains, further underscored the clinical heterogeneity among phenotypes. Overall, these findings suggest that visual scale-based MRI phenotyping may serve as a practical approach in resource-limited clinical settings where advanced methods are unavailable. However, the results must be interpreted with caution and require validation in larger independent cohorts. Further research is necessary to clarify the relationship between scale- and thickness-based phenotyping across different disease stages and to investigate discrepancies in demographic, apolipoprotein E (APOE)-related, and clinical phenotype patterns in this Serbian sample compared to other populations.},
}

@article {pmid41944116,
year = {2026},
author = {Özcan, F},
title = {Voice Biomarkers: Cognitive Impairment, including Alzheimer's Disease, Dementia, or Mild Cognitive Impairment: Introduction to Peripheral Neuropathy.},
journal = {Current Alzheimer research},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672050454281260307134058},
pmid = {41944116},
issn = {1875-5828},
abstract = {INTRODUCTION/OBJECTIVE: Alzheimer's disease (AD) can cause certain nervous disorders, which in turn can lead to voice disorders and abnormal values for certain acoustic parameters. Mild cognitive impairment (MCI) is probably the early stage of the disease. Dementia is one of the causes of Alzheimer's disease. Whether or not there is a link between these three cognitive impairments, lesions affecting the vocal cords or articulators can be caused by neurological structures that influence phonation. The potential of biomarkers in the detection of cognitive impairment is remarkable. In our study, we will examine vocal biomarkers obtained from the extraction of acoustic features. The aim of this study is to combine vocal biomarkers with cognitive diseases.

METHODS: The standardised dataset used has recently been made publicly available. Cognitive impairment, including Alzheimer's disease, dementia, or MCI, is diagnosed from /a/ and diadochokinesis-pataka vocalisations using Mel-Frequency Cepstral Coefficients (MFCCs) transformed into 2D scalogram images. For processing, we will use the pre-trained OpenL3 network, and our less resource-intensive network called Op1Net to classify diseased and healthy groups.

RESULTS: A significant difference was observed compared to the control group. For the /a/ vocalisation, classification accuracy across all ages and genders was 82.1%, and the AUC value was 88.3%, while for diadochokinesis-pataka, accuracy was 69.8% and the AUC value was 75.4%. In the group of women over 55 years of age, the accuracy was 80.93%, and the AUC value was 87.12%.

DISCUSSION: Performance results clearly show that there is a correlation between the voice and the neurodegenerative disease AD, dementia, or MCI. We can see that the results of the data classification, including all ages and genders, for the sound /a/ are higher than those for the 'pataka' vocalisations. The prolonged vowel provides more information about the disease.

CONCLUSION: This preliminary multidisciplinary study clearly demonstrates the existence of a link between neurological disease and the voice, and raises several questions concerning the nervous system, particularly the vagus nerve and associated neuropathy.},
}

@article {pmid41944134,
year = {2026},
author = {Vijayalakshmi, A and Prabhakar, V},
title = {Pathogenic Protein Post-Translational Modifications in Alzheimer's Disease: Mechanisms and Therapeutic Strategies.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273448693251223103034},
pmid = {41944134},
issn = {1996-3181},
abstract = {BACKGROUND: Alzheimer's Disease (AD) pathology involves much more than just Amyloid- Beta (Aβ) and tau (Tau) deposition. A broad network of Post-Translational Modifications (PTMs) drives pathogenic protein conformations that accelerate neuroinflammation, synaptic dysfunction, aggregation, and trans-neuronal spread. Characterising PTM-dependent biochemical signatures allows earlier diagnosis and supports the development of molecularly targeted therapies.

METHODS: A comprehensive review was performed with clinical-trial registries, high-confidence proteomic repositories, and major bibliographic databases from 2000 to 2024, in line with PRISMA guidelines. Bioinformatic tools, curated PTM databases, protein-interaction networks, and computational structure-prediction platforms were utilized to analyse PTM interactions, pathway convergence, and structural impacts.

RESULTS: These include multiple PTMs such as phosphorylation, acetylation, truncation, glycation, oxidation, nitration, ubiquitination, SUMO conjugation, and O-GlcNAc modification that reshape Tau and Aβ solubility, trafficking, aggregation propensity, and clearance efficiency. Human brain proteomics has revealed stage-specific PTM signatures, providing evidence for a combinatorial "PTM code" that dictates disease progression. These PTM-defined proteoforms have directly informed biomarker development, e.g., plasma/Cerebrospinal Fluid (CSF) phosphorylated tau (p-tau) 217/231, and have improved therapeutic precision, including antibodies targeting pyroglutamatemodified Aβ. Therapeutic innovation is targeting kinases, phosphatases, acetylation machinery, OGlcNAc cycling enzymes, oxidative stress pathways, and proteostasis networks alongside RNAbased tau-lowering agents, PTM-guided immunotherapies, and rational combination strategies.

CONCLUSION: PTMs are a central, actionable dimension linking molecular pathology, biomarker specificity, and therapeutic response in AD. The integration of PTM signatures into discovery pipelines and clinical-trial frameworks may help to advance precision diagnostics and yield more effective, disease-modifying interventions.},
}

@article {pmid41944207,
year = {2026},
author = {Dinter, E and Margraff, JL and Schniewind, I and Reinhard, N and , and Reichmann, H and Bräuer, S and Falkenburger, BH},
title = {CSF alpha-Synuclein Seed Amplification Assay results in routine clinically collected samples.},
journal = {Journal of Parkinson's disease},
volume = {},
number = {},
pages = {1877718X261431201},
doi = {10.1177/1877718X261431201},
pmid = {41944207},
issn = {1877-718X},
abstract = {BackgroundLewy Body pathology can be detected by alpha-synuclein-Seed Amplification Assay (αSyn-SAA) in cerebrospinal fluid (CSF) with high sensitivity and specificity in cohort studies. Yet, little is known about the results that can be expected from αSyn-SAA in CSF in samples outside cohort studies as obtained in clinical routine.ObjectiveThis study analyzed the concordance of αSyn-SAA findings in CSF with clinical diagnosis in patients from clinical routine with diverse neurologic and psychiatric conditions.MethodsIn this cross-sectional study, CSF from patients who underwent lumbar puncture for therapeutic or diagnostic purposes were tested in αSyn-SAA. Analysis included binary αSyn-SAA findings, data collected during neurological examination, and structured medical history.ResultsAll 356 participants (Mean Age 67.1 years, SD = 16.2; 55.9% male) were included in the primary analysis, including 90 patients with Parkinsonian syndromes, 139 with predominant cognitive disorders, 25 with other movement disorders, 35 with inflammatory or (para)neoplastic syndromes, and 67 with further diseases. αSyn-SAA was positive in all samples from patients with Parkinson's disease (41), dementia with Lewy bodies (30), pure autonomic failure (4), and in a subset of patients with Alzheimer's disease (13/46), normal pressure hydrocephalus (7/14) and others.ConclusionsαSyn-SAA findings show high concordance with a clinical diagnosis of PD and DLB. Findings are comparable to results from well-characterized cohort studies, supporting potential diagnostic value in future clinical routine. Challenges may result from the fact that αSyn-SAA detect LB co-pathology that is known from neuropathological studies for several neurodegenerative diseases.},
}

@article {pmid41944257,
year = {2026},
author = {Alshaikhsalama, A and Thompson, K and Hashim, H and Patel, KG},
title = {Analyzing the association between age-related macular degeneration, retinal vascular occlusions, and dementia.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261438587},
doi = {10.1177/11206721261438587},
pmid = {41944257},
issn = {1724-6016},
abstract = {PurposeTo investigate the association between age-related macular degeneration (AMD), retinal artery occlusion (RAO), and retinal vein occlusion (RVO) and the future development of Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia (ACD).MethodsRetrospective propensity score-matched cohort study using TriNetX, a confederated healthcare network. The study population included 91,296 AMD, 15,372 RAO, 35,862 RVO, and 3,076,291 population control (PC) patients aged 65 and older. Propensity score matching was applied to control for baseline demographics and health characteristics. The primary outcome was the measured risk of developing AD, VaD, and ACD following incident diagnosis of AMD, RAO, or RVO.Major FindingsAMD was associated with a significantly elevated risk of AD (HR, 1.25; 95% CI, 1.17-1.34; P < 0.001), VaD (HR, 1.20; 95% CI, 1.11-1.31; P < 0.001), and ACD (HR, 1.12; 95% CI, 1.08-1.16; P < 0.001) following diagnosis with an average follow up of 45.0 ± 36.7 months. RVO patients also displayed higher risks across all dementia types (AD: HR, 1.46; 95% CI, 1.22-1.74; P < 0.001; VaD: HR, 1.51; 95% CI, 1.23-1.87; P < 0.001; ACD: HR, 1.34; 95% CI, 1.22-1.47; P < 0.001) with an average follow up of 46.6 ± 37.9 months.ConclusionsRetinal disease diagnoses may correlate with increased dementia risk. While AMD and RVO are associated with all dementias (AD, VaD, and ACD), RAO did not increase dementia risk.},
}

@article {pmid41944296,
year = {2026},
author = {Gong, W and Hui, W and Qiao, S and Ji, Q and Liu, M and Zhang, B and Liu, D and Wu, Y and Zhou, S},
title = {Brain and Liver Dual-Targeting Oridonin Nanoparticles to Enhance Aβ Clearance for Alzheimer's Disease Therapy.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e23458},
doi = {10.1002/advs.202523458},
pmid = {41944296},
issn = {2198-3844},
support = {2023-ZDYJSY-001//Shaanxi Administration of Traditional Chinese Medicine/ ; 2023JSYX16//Research Project from Air Force Medical University/ ; //Key Laboratory of New Drug Delivery System and New Technology for Formulation/ ; 82073775//National Natural Science Foundation of China/ ; 82071515//National Natural Science Foundation of China/ ; SZY-KJCYC-2025-ZY-013//Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine/ ; },
abstract = {The brain and liver are both critical organs involved in the pathogenesis of Alzheimer's disease (AD), particularly in the modulation of amyloid-beta (Aβ) metabolism and neuroinflammation. Based on this, a multifunctional nanodrug delivery system, termed OAF, was developed by encapsulating oridonin (ORI) into apoferritin (ApoFn), enabling simultaneous targeting of both brain and the liver through transferrin receptor 1 (TfR1). OAF upregulated the expression of low-density lipoprotein receptor-related protein 1 (LRP1) in cerebral capillary endothelial cells and hepatic parenchymal cells to promote Aβ clearance from the brain and subsequent hepatic degradation. In AD mice, OAF treatment markedly reduced Aβ deposition, neuroinflammation, and cognitive impairment, while ameliorating inflammation, oxidative stress, and mitochondrial dysfunction in both brain and liver. Overall, OAF synergistically combined Aβ clearance, anti-inflammatory, and antioxidant mechanisms, offering a novel therapeutic strategy for AD.},
}

@article {pmid41944313,
year = {2026},
author = {Chen, J and Li, B and Wang, Y and Zhu, F and Yang, W and Fu, X and Man, T and Wu, Q and Ren, K and Deng, S},
title = {Biolipid Film-Fused Electrochemiluminescence for Multipurpose In Situ Bioassays.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e24242},
doi = {10.1002/advs.202524242},
pmid = {41944313},
issn = {2198-3844},
support = {22374076//National Natural Science Foundation of China/ ; 22204077//National Natural Science Foundation of China/ ; 22504061//National Natural Science Foundation of China/ ; BK20231455//Natural Science Foundation of Jiangsu Province/ ; 2025201001//Fundamental Research Funds for the Central Universities/ ; 30924010201//Fundamental Research Funds for the Central Universities/ ; 30924010809//Fundamental Research Funds for the Central Universities/ ; TMSK-2024-115//Open Research Program of National Major Scientific and Technological Infrastructure for Translational Medicine/ ; KYCX24_0688//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; SKLACLS2412//State Key Laboratory of Analytical Chemistry for Life Science/ ; SKLACLS2402//State Key Laboratory of Analytical Chemistry for Life Science/ ; },
abstract = {Electrochemiluminescence (ECL) is intrinsically a surface-state-sensitive strategy, yet its seamless synergy with soft biomembranes remains sparsely explored. Herein, a biolipid-bound, membrane-interactive scaffold is built upon an ECL-emissive artificial nanochannel and smoothly blended into supported phospholipid bilayers containing cholesterol and diversified natural or synthetic lipids. Such bilayer-bridged assemblies preserve efficient emission while permitting dynamic membrane remodeling. The resulting biointerface enables label-free profiling of cytomembrane-active species, including divalent cations, amphiphilic pharmaceuticals, and pore-forming peptides, through real-time isotherm and kinetic analysis. By further integrating phospholipid-pendant recognition motifs, femtomolar detection of Alzheimer's disease biomarkers (β-amyloid polypeptide and tau protein) is achieved. Moreover, vesicle-mediated membrane merging embeds ECL emitters into living-cell plasmalemma, affording surface-confined single-cell visualization using endogenous oxygen as the coreactant. Collectively, this biointerface-compatible ECL paradigm enables multiplexed monitoring of molecular, membranous, and cellular processes via membrane-structural modulation.},
}

@article {pmid41944317,
year = {2026},
author = {Shao, L and Wang, F and Wang, Y and Du, J and Cao, W and Zhang, Q and Zhao, F and Wang, J and Fan, W and Zhou, Y and Wang, B and Pang, X and Yan, L},
title = {Rational design of environment-sensitive fluorescent probes for butyrylcholinesterase and their application in biological imaging.},
journal = {Analytical methods : advancing methods and applications},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6ay00158k},
pmid = {41944317},
issn = {1759-9679},
abstract = {Butyrylcholinesterase (BChE) is closely associated with Alzheimer's disease (AD), with its expression significantly elevated in the brains of AD patients. This enzyme has emerged as a potential biomarker for monitoring AD progression. Therefore, developing a reliable chemical tool to detect BChE both in vitro and in vivo is of considerable interest. In this study, we rationally designed a series of environmentally sensitive fluorescent probes targeting BChE, based on a highly potent, selective, and reversible BChE inhibitor. Among these, the most promising probe ESP4 demonstrated an ultrafast response to BChE with exceptional sensitivity (LOD = 1.81 nM), enabling high-precision detection of BChE. Additionally, ESP4 maintained robust inhibitory activity against BChE in the low nanomolar range (IC50 = 71.78 ± 1.90 nM). Notably, ESP4 exhibited excellent selectivity for BChE, showing no interference from other biological species, including acetylcholinesterase (AChE). The probe also accurately measured the IC50 of tacrine (7.83 nM), a standard BChE inhibitor, demonstrating its reliability in evaluating BChE inhibition. Due to its high sensitivity, rapid response, and superior selectivity, ESP4 enabled real-time imaging of BChE in biological systems such as cells, zebrafish, and AD mouse models. Collectively, these findings highlighted ESP4 as a valuable tool for BChE detection, contributing to a deeper understanding of the physiological role of BChE in health and disease.},
}

@article {pmid41944335,
year = {2026},
author = {Hu, M and Knopman, DS and Therneau, T and Fought, AJ and Hofrenning, E and Lowe, VJ and Petersen, RC and Algeciras-Schimnich, A and Jack, CR and Stricker, NH and Mielke, MM and Vemuri, P and Graff-Radford, J},
title = {Breakpoints in Alzheimer's disease biomarkers and cognition across the aging spectrum: The Mayo Clinic Study of Aging.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71227},
doi = {10.1002/alz.71227},
pmid = {41944335},
issn = {1552-5279},
support = {P30 AG0062677/AG/NIA NIH HHS/United States ; RF1 AG069052/AG/NIA NIH HHS/United States ; U01 AG006786/AG/NIA NIH HHS/United States ; R01AG041851/AG/NIA NIH HHS/United States ; R01AG058738/AG/NIA NIH HHS/United States ; //GHR Foundation/ ; },
mesh = {Humans ; Male ; Biomarkers/blood ; Female ; *Alzheimer Disease/diagnostic imaging/blood ; Aged ; Amyloid beta-Peptides/blood ; tau Proteins/blood ; Positron-Emission Tomography ; *Aging ; Aged, 80 and over ; *Cognition/physiology ; Middle Aged ; Glial Fibrillary Acidic Protein/blood ; Neurofilament Proteins/blood ; Peptide Fragments/blood ; Hippocampus/pathology/diagnostic imaging ; Cohort Studies ; },
abstract = {INTRODUCTION: We examined when Alzheimer's disease biomarkers become informative by identifying age-related breakpoints with slope-changing trajectories.

METHODS: In 2082 Mayo Clinic Study of Aging participants, we modeled plasma amyloid beta (Aβ)42/40, phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid/tau positron emission tomography (PET), hippocampal volume (HVa), and global cognition. Generalized additive models described age trends; Davies' test and piecewise linear regression estimated breakpoints. A C2N subsample (n = 462) provided mass-spectrometry plasma markers (p-tau181, p-tau217, their ratios, Aβ42/40).

RESULTS: In the full cohort, Aβ42/40, HVa, and cognition declined with age; p-tau181, NfL, GFAP, and amyloid/tau PET increased. We observed single breakpoints (years, 95% CI): GFAP 68.1 (63.5-71.8), NfL 70.7 (65.9-75.6), p-tau181 67.2 (60.3-70.3), amyloid PET 62.3 (56.2-69.3), HVa 68.1 (63.1-71.9), cognition 59.8 (55.4-66.0); tau PET showed none. In the mass-spectrometry subset, p-tau217 and p-tau181 broke at 72.6; their ratios and Aβ42/40 showed no breakpoints.

DISCUSSION: Breakpoints cluster near late midlife, suggesting windows for screening and monitoring.},
}

Humans
Male
Biomarkers/blood
Female
*Alzheimer Disease/diagnostic imaging/blood
Aged
Amyloid beta-Peptides/blood
tau Proteins/blood
Positron-Emission Tomography
*Aging
Aged, 80 and over
*Cognition/physiology
Middle Aged
Glial Fibrillary Acidic Protein/blood
Neurofilament Proteins/blood
Peptide Fragments/blood
Hippocampus/pathology/diagnostic imaging
Cohort Studies

@article {pmid41944346,
year = {2026},
author = {Singh, A and Sahu, SK and Sah, AK},
title = {Natural Chiral Scaffolds in Alzheimer's Disease: Therapeutic Potential, Mechanism, and Clinical Aspects.},
journal = {BioMed research international},
volume = {2026},
number = {1},
pages = {e5968529},
pmid = {41944346},
issn = {2314-6141},
mesh = {Humans ; *Alzheimer Disease/drug therapy/metabolism/pathology ; *Biological Products/therapeutic use/chemistry/pharmacology ; Stereoisomerism ; Blood-Brain Barrier/metabolism/drug effects ; Animals ; Amyloid beta-Peptides/metabolism ; Drug Discovery ; },
abstract = {Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive impairment, amyloid-β deposition, tau pathology, oxidative stress, neuroinflammation, and dysfunction of synapses. Current therapeutic options are largely symptomatic and lack disease-modifying efficacy. Target binding, pharmacokinetics, and therapeutic efficacy in AD are all significantly impacted by the stereochemistry of many bioactive natural scaffolds, which are enantiomerically defined molecules. Due to the complexity of their stereochemical structures and their multiple-target pharmacological attributes, natural chiral scaffolds have received significant attention as lead compounds to treat AD. The chirality has a critical impact on target selectivity, receptor binding, blood-brain barrier permeability, and pharmacokinetic behavior. By combining stereochemistry with pharmacological and clinical data, it is possible to expedite the discovery of safer and more effective disease-modifying therapies, thus making chiral natural products attractive for AD drug discovery in the future.},
}

Humans
*Alzheimer Disease/drug therapy/metabolism/pathology
*Biological Products/therapeutic use/chemistry/pharmacology
Stereoisomerism
Blood-Brain Barrier/metabolism/drug effects
Animals
Amyloid beta-Peptides/metabolism
Drug Discovery

@article {pmid41944421,
year = {2026},
author = {Rodrigues, JFR and Rodrigues, LP and Teshima, T and Yang, S and Wu, Y and Hu, X and Abarca, GIF and da Cruz, KCT and Rodriguez, MFS and Rubatino, FVM and Yamakawa, M and de Godoy, MF and Filho, GMA},
title = {Loneliness as an Interface Between Alzheimer's Disease and Suicidal Behaviour: A Systematic Review, Meta-Analysis and Meta-Analytic Factor Analysis.},
journal = {Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society},
volume = {26},
number = {3},
pages = {e70165},
doi = {10.1111/psyg.70165},
pmid = {41944421},
issn = {1479-8301},
mesh = {Humans ; *Alzheimer Disease/psychology/epidemiology ; *Loneliness/psychology ; *Suicidal Ideation ; Depression/psychology ; Factor Analysis, Statistical ; *Suicide/psychology ; *Suicide, Attempted/psychology ; Aged ; Risk Factors ; },
abstract = {Loneliness is an epidemic affecting mental health across all demographics. It is linked to mental disorders, such as anxiety and depression, and despair, highlighting a significant public health issue as persons feel more disconnected in a connected world. This study aims to investigate the relationship between loneliness, Alzheimer's disease and suicidal behaviour. This review was systematised in a dichotomous manner. Therefore, two systematic reviews were initially carried out following the PRISMA statement. The loneliness was understood as feeling lonely. One group searched for associations between loneliness and Alzheimer's disease and the other between loneliness and suicidal behaviour, with a consecutive meta-analysis. After that, it was searched for between the two groups to seek loneliness, such as an interface in meta-analytic factor analysis. Depression is the most studied and cited factor associated with loneliness as a link between Alzheimer's disease and suicide. Loneliness demonstrated association with Alzheimer's disease (OR = 1.89, 95% CI 1.57-2.28; p < 0.001); suicidal ideation (OR = 2.17, 95% CI 1.88-2.51; p < 0.001); suicidal planning (OR = 2.36, 95% CI 1.91-2.92; p < 0.001); suicide attempt (OR = 2.54, 95% CI 2.13-3.04; p < 0.001); and suicide (OR = 4.9, 95% CI 4.4-5.5; p < 0.001). Entrapment, hopelessness, insomnia and stress demonstrated significative correlation (r > 0.40; p < 0.001) with loneliness in the interface between AD and suicidal behaviour. Loneliness has been identified as a comorbid factor between AD and suicide. To prevent both AD and suicide, it is essential to monitor levels of stress, insomnia, feelings of entrapment and hopelessness. The triad of loneliness, hopelessness and insomnia seems to represent the greatest risk profile.},
}

Humans
*Alzheimer Disease/psychology/epidemiology
*Loneliness/psychology
*Suicidal Ideation
Depression/psychology
Factor Analysis, Statistical
*Suicide/psychology
*Suicide, Attempted/psychology
Aged
Risk Factors

@article {pmid41944428,
year = {2026},
author = {Hemmy, L and Cevasco-Trotter, A and Silverman, M and Wang, S and Yuan, SH},
title = {Music therapy interest in patients with Alzheimer's disease and Alzheimer's disease related dementia: A survey study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261437271},
doi = {10.1177/13872877261437271},
pmid = {41944428},
issn = {1875-8908},
abstract = {BackgroundMusic therapy can be an effective psychosocial intervention for people with Alzheimer's disease (AD) and Alzheimer's disease related dementia (ADRD). However, there is a lack of literature regarding people with AD and ADRD's interest in music therapy.ObjectiveThe purpose of this study was to examine interest in music therapy among patients receiving care at an outpatient memory clinic.MethodsA total of 70 patients receiving outpatient services at a university memory clinic completed a researcher-designed one-page survey assessing demographic information and interest in music therapy. Clinic staff recruited participants at check-in for their regularly scheduled appointments.ResultsParticipants were a mean 74.4 years old (SD = 9.5 years). Most participants identified as White (90%), had access to reliable internet (89.7%), and had not previously heard of music therapy (56.7%). Participants indicated they would prefer individual music therapy (58.2%) over group music therapy (10.9%). Participants tended to have low interest levels when asked to rate their interest in receiving music therapy in both in-person or teletherapy formats.ConclusionsAlthough music therapy can help maintain cognitive abilities in older adults, participants receiving care in our outpatient memory clinic expressed low interest in receiving music therapy in person or via telehealth. However, many participants were unfamiliar with music therapy, underscoring the need for education and advocacy to increase awareness and access to care. Implications, limitations, and suggestions for future research are provided.},
}

@article {pmid41944433,
year = {2026},
author = {Luo, X and Li, H and Yu, Y and Sheng, D and He, Z and Li, L and Su, Y and Zhu, Z and Wei, M and Ping, J and Huang, C and Jiang, T and Wang, Y and Liu, X and Wang, Y},
title = {Changes in frailty and its association with dementia risk in four prospective cohorts.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261430305},
doi = {10.1177/13872877261430305},
pmid = {41944433},
issn = {1875-8908},
abstract = {BackgroundPrevious studies found baseline frailty is a key risk factor for dementia, but changes in frailty during follow-up were less considered. Clarifying the impact of frailty change may help prevent or delay dementia.ObjectiveThis study investigates frailty changes and their link to dementia risk.MethodsIn this cohort study, we used four prospective cohorts: Health and Retirement Study (HRS), English Longitudinal Study of Ageing (ELSA), China Health and Retirement Longitudinal Study (CHARLS), and Ageing and Retirement in Europe (SHARE). The Fried frailty phenotype classified participants as: robust, pre-frail, and frail. Dementia was defined as those with a combination of cognitive and functional impairment, or those who had self-reported doctor-diagnosed dementia. Cox proportional-hazards model was used to examine the association of changes in frailty with dementia risk.ResultsAfter exclusions, 28,679 participants from an initial sample of 134,834 were included in the analysis. Compared with stable robust participants, those progressing to pre-frail/frail had higher dementia risk (HRS, HR 2.05, 95% CI 1.54-2.72; ELSA, HR 2.24, 95% CI 1.20-4.17; CHARLS, HR 2.85, 95% CI 1.42-5.73; SHARE, HR 1.78, 95% CI 1.34-2.37). Conversely, frail participants who recovered to robust/pre-frail had lower risk than stable frail.ConclusionsAs the frailty status advances, the risks of incident dementia escalate. In contrast, when the frailty status recovers, the risks of incident dementia reduce.},
}

@article {pmid41944642,
year = {2026},
author = {Kemsawasd, V and Thangsiri, S and Sahasakul, Y and Aursalung, A and Inthachat, W and Temviriyanukul, P and Kittibunchakul, S and Suttisansanee, U},
title = {Evaluation of the underutilized Malpighia glabra L. fruits as a future functional food: nutritional composition, phenolic profile, biological activities, and synergistic effects with pharmaceutical drugs.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo03782d},
pmid = {41944642},
issn = {2042-650X},
abstract = {Malpighia glabra L., commonly known as acerola or Barbados cherry, is a non-commercial tropical fruit species in Thailand that is primarily consumed fresh by local communities. Limited scientific data have restricted its potential for future food applications. In this study, we investigated the nutritional composition, phenolic profiles, and in vitro biological activity of M. glabra fruits. Results demonstrated that the ripened fruits (100 g fresh weight) provided low energy (36.9 kcal) with negligible fat content but exceptionally high vitamin C content (838 mg). The ethanolic extract exhibited strong antioxidant activities as examined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay (250.98 µmol Trolox equivalent (TE) per g dry weight (DW)), ferric ion reducing antioxidant power (FRAP) assay (642.35 µmol TE per g DW), and oxygen radical absorbance capacity (ORAC) assay (443.90 µmol TE per g DW). These activities were attributed to the phenolic composition, of which rutin was the predominant compound, as detected by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). The extract also demonstrated in vitro inhibition of α-glucosidase, with a half-maximal inhibitory concentration (IC50) of 4.81 mg mL[-1], and β-secretase, with an IC50 value of 5.45 mg mL[-1]. Synergistic interactions were observed in vitro between the extract and acarbose (an anti-diabetic drug) and the extract and donepezil (an anti-Alzheimer's drug). These findings characterize the nutritional composition and in vitro bioactivities of ripened M. glabra fruits, supporting further investigation into their potential development as functional food ingredients.},
}

@article {pmid41944714,
year = {2026},
author = {Ashok, AH and Field, S and Ramakrishnan, NK and Thompson, S and O'Brien, JT and Aigbirhio, FI},
title = {P2X7 receptor and neuroinflammation in neurodegenerative disorders: an autoradiography study with [18F]JNJ-64413739.},
journal = {Nuclear medicine communications},
volume = {},
number = {},
pages = {},
pmid = {41944714},
issn = {1473-5628},
abstract = {BACKGROUND: Neuroinflammation plays a crucial role in neurodegenerative disorders such as Alzheimer's disease. The P2X7 receptor (P2X7R), expressed on microglia, is involved in neuroinflammatory responses. Despite evidence of P2X7R upregulation in Alzheimer's disease models, its role in human Alzheimer's disease remains unclear. The PET radioligand [18F]JNJ-64413739 enables the assessment of P2X7R distribution in post-mortem Alzheimer's disease brain tissue.

METHODS: Post-mortem brain tissue from Alzheimer's disease and control subjects was obtained. [18F]JNJ-64413739 was synthesised and applied to tissue sections from the temporal and parietal cortex. Autoradiography was conducted with and without the P2X7R antagonist JNJ54173717.

RESULTS: [18F]JNJ-64413739 binding was observed across all brain regions, with effective blocking confirming specificity. No significant differences were found between Alzheimer's disease and controls in the temporal (P = 0.84) or parietal cortex (P = 0.90) in the first experiment. The second experiment, using a modified protocol also did not reveal a significant difference between controls and Alzheimer's disease in either temporal (P = 0.66) or parietal cortex (P = 0.38). White matter exhibited significantly higher binding than grey matter (P < 0.01), but no disease-specific differences were noted.

CONCLUSION: This study demonstrates P2X7 receptor-specific binding of [18F]JNJ-64413739 but finds no significant differences between post-mortem tissue of Alzheimer's disease cases and controls. These findings suggest that while the tracer shows promising in vitro characteristics, the role of P2X7R in Alzheimer's disease pathology and its utility as a biomarker require further validation through in vivo imaging studies across disease stages.},
}

@article {pmid41944723,
year = {2026},
author = {Tang, C and Sun, X and Tang, A and Ruan, W and Liu, F and Fang, H and Gai, Y and Liang, Z and Su, Y and Wang, X and Lan, X and , and , },
title = {Decoupling Alzheimer Disease Pathologic Abnormalities at PET with Improved Clinical Relevance by Interpretable Adversarial Decomposition Learning.},
journal = {Radiology},
volume = {319},
number = {1},
pages = {e252321},
doi = {10.1148/radiol.252321},
pmid = {41944723},
issn = {1527-1315},
mesh = {Humans ; *Alzheimer Disease/diagnostic imaging/pathology ; *Positron-Emission Tomography/methods ; Female ; Male ; Aged ; Retrospective Studies ; Brain/diagnostic imaging/pathology ; Amyloid beta-Peptides/metabolism ; tau Proteins/metabolism ; Aged, 80 and over ; *Deep Learning ; Neuroimaging/methods ; Clinical Relevance ; },
abstract = {Background Template-based PET metrics quantify Alzheimer disease (AD) amyloid-β (Aβ) and tau burden but compress whole-brain data into a single scalar, overlooking disease heterogeneity and sometimes causing imaging-clinical discordance. Artificial intelligence (AI) approaches capture richer patterns but often lack biologic interpretability. Purpose To develop and validate an interpretable deep-learning framework that separates AD-specific abnormalities from physiologic uptake using pathophysiologic constraints, generating a clinically meaningful AI biomarker. Materials and Methods In this retrospective study, Aβ and tau PET scans from the Alzheimer's Disease Neuroimaging Initiative, Australian Imaging Biomarkers and Lifestyle study, Global Alzheimer's Association Interactive Network, and the authors' center were analyzed. An adversarial decomposition learning (ADL) network generated voxel-level pathologic maps and an AD adversarial decomposition (ADAD) score. Discriminatory performance for clinical AD versus cognitively normal individuals was evaluated using the area under the curve (AUC). Clinical relevance was assessed with cognitive, hippocampal volume, cerebrospinal fluid (CSF), and neuropathologic measures using longitudinal mixed-effects models and Spearman correlations. Results The study included 7457 Aβ PET scans from 3595 patients (median age, 71.4 years; IQR, 65.7-77.0 years; 1637 female patients) and 1894 tau PET scans from 1127 patients (median age, 72.0 years; IQR, 66.9-78.5 years; 545 female patients). External testing AUCs were 0.94 (95% CI: 0.89, 0.98) for Aβ and 0.98 (95% CI: 0.95, 1.00) for tau. ADL generated interpretable pathologic attribution maps that correlated with expert rankings (Aβ and tau, Spearman ρ = 0.79 and 0.63, respectively). Although Centiloid and CenTauRz showed numerically higher correlations with postmortem neuropathologic structure and stronger associations with CSF biomarkers, the ADAD score demonstrated independent baseline and longitudinal associations with cognitive outcomes and hippocampal atrophy after adjustment. Conclusion Pathophysiologic-constrained ADL provided interpretable, personalized pathologic maps and an AI-derived ADAD score that more closely linked PET pathologic abnormalities with multimodal clinical measures. © RSNA, 2026 Supplemental material is available for this article.},
}

Humans
*Alzheimer Disease/diagnostic imaging/pathology
*Positron-Emission Tomography/methods
Female
Male
Aged
Retrospective Studies
Brain/diagnostic imaging/pathology
Amyloid beta-Peptides/metabolism
tau Proteins/metabolism
Aged, 80 and over
*Deep Learning
Neuroimaging/methods
Clinical Relevance

@article {pmid41944915,
year = {2026},
author = {Kimura, K and Driscoll, I and Cook, N and Shahzad, S and Betthauser, TJ and Johnson, SC and Asthana, S and Gallagher, CL and Hermann, BP and Sager, MA and Blennow, K and Zetterberg, H and Carlsson, CM and Kollmorgen, G and Okonkwo, OC},
title = {Associations between air pollution and markers of neuroinflammation, synaptic dysfunction and core Alzheimer's disease pathology vary by APOE genotype.},
journal = {Neurotoxicity research},
volume = {44},
number = {2},
pages = {},
pmid = {41944915},
issn = {1476-3524},
support = {R01AG077507/AG/NIA NIH HHS/United States ; R01AG027161/AG/NIA NIH HHS/United States ; P30AG062715/AG/NIA NIH HHS/United States ; R01AG062167/AG/NIA NIH HHS/United States ; },
}

@article {pmid41944966,
year = {2026},
author = {Riaz, M and Qadir, H and Noman, M and Ahmed, S and Shah, FA and Malik, MU and Bashir, K and Farooq, U and Irshad, N},
title = {Mechanistic Insights into Bergapten by Modulation of Filamin A and GSK3β in STZ Induced Alzheimer's Disease: An Integrated In Silico, In Vitro and In Vivo Study.},
journal = {Neurochemical research},
volume = {51},
number = {2},
pages = {},
pmid = {41944966},
issn = {1573-6903},
}

@article {pmid41945082,
year = {2026},
author = {Falangola, MF and Voltin, J and Cole, M and Nietert, PJ and Liu, F and Iqbal, K and Jensen, JH},
title = {Corrigendum to Diffusion MRI measures detect brain microstructure changes due to early treatment with neurotrophic peptide mimetic P021 in the 3xTg-AD mouse model of Alzheimer's disease. Magn Reson Imaging. 2026 Jun;129:110641 Page: 9.},
journal = {Magnetic resonance imaging},
volume = {},
number = {},
pages = {110677},
doi = {10.1016/j.mri.2026.110677},
pmid = {41945082},
issn = {1873-5894},
}

@article {pmid41945181,
year = {2026},
author = {Sayehmiri, F and Parvenous, M and Vakili, K and Ebrahimi, R and Batool, Z and Bazgir, N and Kazemi, K and Moafi, M and Ebrahimi, MJ and Hajiesmaeili, M},
title = {The role of 2-Oxoglutarate dehydrogenase complex mitochondrial enzyme in alzheimer's disease: a literature review and bioinformatics workflow.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41945181},
issn = {1573-7365},
}

@article {pmid41945238,
year = {2026},
author = {Nabi, SU and Rasool, I and Khan, A and Haq, AU and Hussain, I and Khan, MS and Majid, S and Rashid, S and Rashid, SM and Sehar, N and Rather, MA and Rehman, MU},
title = {Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.},
journal = {Metabolic brain disease},
volume = {41},
number = {1},
pages = {},
pmid = {41945238},
issn = {1573-7365},
}

@article {pmid41945446,
year = {2026},
author = {Li, TT and Wang, G and D'Amico, AM and Christensen, LA and Vasquez, KM},
title = {Aging alters DNA structure-induced genetic instability in mice.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {15},
pages = {e2600482123},
doi = {10.1073/pnas.2600482123},
pmid = {41945446},
issn = {1091-6490},
support = {CA093729//NIH/NCI/ ; },
mesh = {Animals ; *Aging/genetics ; Mice ; *Genomic Instability ; *DNA, Z-Form/genetics/chemistry ; Mice, Transgenic ; Apoptosis/genetics ; DNA End-Joining Repair ; Mice, Inbred C57BL ; Nucleic Acid Conformation ; },
abstract = {Repetitive DNA sequences can adopt alternative (i.e., non-B) DNA structures, which represent an endogenous source of genetic instability. Z-DNA, a non-B-DNA structure, has been implicated in the development of age-related genetic disorders such as cancer and Alzheimer's disease. Previously, we found that Z-DNA is mutagenic in mammals; however, the impact of age on Z-DNA-induced genetic instability has not yet been explored. Here, we investigated the effects of aging on Z-DNA-induced genetic instability using a transgenic mutation reporter mouse model. We found that Z-DNA was more mutagenic than control B-DNA in all tissues tested. Contrary to initial expectations, Z-DNA-induced deletions decreased with age, whereas the point mutation frequencies remained unchanged. Our results suggest that while the cleavage activities on Z-DNA were similar in both age groups, the reduction of Z-DNA-induced deletion mutants in aged mice was due to attenuated DNA end-joining efficiency, which is required for the mutagenic processing of Z-DNA, and increased apoptosis. These results provide mechanistic insight into age-associated genetic instability and the aging-cancer link.},
}

Animals
*Aging/genetics
Mice
*Genomic Instability
*DNA, Z-Form/genetics/chemistry
Mice, Transgenic
Apoptosis/genetics
DNA End-Joining Repair
Mice, Inbred C57BL
Nucleic Acid Conformation

@article {pmid41945476,
year = {2026},
author = {Zhang, Y and Deng, Q},
title = {Revisiting the inverse relationship between breast cancer and Alzheimer's disease: insights and implications.},
journal = {Neuroepidemiology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1159/000551898},
pmid = {41945476},
issn = {1423-0208},
}

@article {pmid41945799,
year = {2026},
author = {Barnwal, N and Dubey, S and Tiwari, P},
title = {Benzimidazole as a Versatile Scaffold for Developing Neurotherapeutics Against Neurodegenerative Diseases.},
journal = {ChemMedChem},
volume = {21},
number = {7},
pages = {e202500869},
doi = {10.1002/cmdc.202500869},
pmid = {41945799},
issn = {1860-7187},
mesh = {Humans ; *Benzimidazoles/chemistry/pharmacology/therapeutic use/chemical synthesis ; *Neurodegenerative Diseases/drug therapy/metabolism ; *Neuroprotective Agents/chemistry/pharmacology/therapeutic use/chemical synthesis ; Animals ; Molecular Structure ; Structure-Activity Relationship ; },
abstract = {Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss, leading to severe cognitive and motor dysfunction. Benzimidazole, a privileged heterocyclic scaffold, has emerged as a promising pharmacophore in modulating key pathological targets across these disorders. In AD, benzimidazole derivatives inhibit cholinesterases, glycogen synthase kinase-3β (GSK-3β), and glutaminyl cyclase (QC), thereby addressing cholinergic dysfunction, tau phosphorylation, and amyloid aggregation. In PD and HD, they act as monoamine oxidase-B (MAO-B) inhibitors, dopamine D1/D2 receptor modulators, and N-methyl D-aspartate receptor antagonists, improving dopaminergic signalling and reducing excitotoxicity. In ALS, benzimidazoles regulate acetylcholine dysfunction and inhibit receptor-interacting protein kinase 1 (RIPK1), limiting neuroinflammation and cell death. Preclinical studies demonstrate potent enzyme inhibition, often with IC50 values in the nanomolar to micromolar range, alongside favourable ADMET properties enabling blood-brain barrier penetration. Clinically, the glutaminyl cyclase inhibitor Varoglutamstat has advanced to Phase II trials for AD, while Riluzole remains the only food and drug administration (FDA)-approved benzimidazole drug for ALS. The structural versatility of benzimidazoles supports their development as multi-target-directed ligands, addressing overlapping mechanisms such as protein aggregation, oxidative stress, and neuroinflammation. Emerging strategies including hybrid molecules, nanocarrier delivery, and AI-driven design may accelerate their clinical translation.},
}

Humans
*Benzimidazoles/chemistry/pharmacology/therapeutic use/chemical synthesis
*Neurodegenerative Diseases/drug therapy/metabolism
*Neuroprotective Agents/chemistry/pharmacology/therapeutic use/chemical synthesis
Animals
Molecular Structure
Structure-Activity Relationship

@article {pmid41945862,
year = {2026},
author = {Gao, H and Hu, Y and Li, L and Moita, ASOH and Wang, X and Meng, Z and Han, Z and Liu, Y},
title = {Self-Assisted Charge Storage-Release Mechanism Enabling Flexible Design of Biomimetic Triboelectric Nanogenerators.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e22836},
doi = {10.1002/advs.202522836},
pmid = {41945862},
issn = {2198-3844},
support = {52575347//National Natural Science Foundation of China/ ; 52205318//National Natural Science Foundation of China/ ; U22A20183//National Natural Science Foundation of China/ ; 2024YFE0105500//International Research Programs and Strategic Innovative Programs of National Key R&D Program of China/ ; 226Z3601G//S&T Program of Hebei/ ; E2025203083//Natural Science Foundation of Hebei Province/ ; BJ2025064//Science Research Project of Hebei Education Department/ ; K202408//Opening Project of the Key Laboratory of Bionic Engineering (Ministry of Education), Jilin University/ ; },
abstract = {Triboelectric nanogenerators (TENGs) have attained a prominent position in the field of renewable energy conversion, and they exhibit immense promise for applications in self-powered sensors and wearable devices. However, their practical power output is highly dependent on triboelectric effectiveness. While micro-nano-structured surfaces have been widely adopted in previous studies to enhance electrostatic effects, such architectures often lead to electric breakdown at the protruding sites, which adversely counteract the original intention. This work introduces a unique Lithium-ion battery-mimetic into a mimosa-inspired TENG with a micro-array surface. By spontaneously regulating charge distribution, it confines the interfacial electric field below the breakdown threshold, thus integrating high flexibility with outstanding electrical performance. Benefiting from a spontaneous charge self-regulation mechanism, the TENG effectively suppresses air breakdown and achieves a high charge density of 396.50 µC m[-2]. Furthermore, this study demonstrates the practicality of the MLBA-TENG in a long-endurance intelligent insole for position monitoring, providing effective long-term protection for special populations such as patients with Alzheimer's disease. The results validate the promising application prospects of the MLBA-TENG in wearable intelligent devices, highlighting its potential to address critical needs in healthcare and mobile electronics.},
}

@article {pmid41945879,
year = {2026},
author = {Gokcal, E and Becker, JA and Horn, MJ and Das, AS and Viswanathan, A and Rosand, J and Polimeni, JR and Sperling, RA and Johnson, KA and Greenberg, SM and Gurol, ME},
title = {Extent of Tau and Its Cognitive Implications in Patients With Cerebral Amyloid Angiopathy Without Cognitive Impairment.},
journal = {Neurology},
volume = {106},
number = {8},
pages = {e214859},
doi = {10.1212/WNL.0000000000214859},
pmid = {41945879},
issn = {1526-632X},
mesh = {Humans ; Male ; Female ; Aged ; *tau Proteins/metabolism ; *Cerebral Amyloid Angiopathy/diagnostic imaging/metabolism/psychology/complications ; Cross-Sectional Studies ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Middle Aged ; Aniline Compounds ; Cognitive Dysfunction/diagnostic imaging/metabolism ; Aged, 80 and over ; *Brain/diagnostic imaging/metabolism ; Carbolines ; Thiazoles ; Neuropsychological Tests ; },
abstract = {BACKGROUND AND OBJECTIVES: Despite a well-established amyloid-tau neurodegeneration cascade in Alzheimer disease (AD), the extent and mechanistic relevance of tau pathology in cerebral amyloid angiopathy (CAA), a disease of vascular amyloid deposition, remain unclear. Focusing on patients with CAA without cognitive impairment to minimize concurrent AD pathology, we hypothesized that tau extent would be greater in patients with CAA than in healthy controls (HCs), largely attributable to amyloid burden, but it would not be associated with CAA-related imaging markers or cognitive scores in CAA.

METHODS: This cross-sectional study included patients with CAA and age-matched and sex-matched HCs, none of whom had cognitive impairment or dementia. All participants underwent brain MRI, Pittsburgh compound B (PiB)-PET for amyloid, and [18]F-flortaucipir (FTP)-PET for tau. Tau extent was estimated based on PET-Braak staging from cortical FTP uptake and categorized into earlier (Braak 0, I-II) vs later (Braak III-VI) PET-Braak stages. Cognitive scores obtained in CAA were standardized z-scores for memory, processing speed, and executive function. Multivariable regression models tested the association of tau extent with (1) CAA diagnosis and amyloid load in the whole cohort [CAA and HC] and (2) amyloid load, CAA-related imaging markers, and cognitive scores within the CAA cohort.

RESULTS: The mean age of patients with CAA (n = 50) was 70.3 ± 7.6 years and of HCs was 69.7 ± 7.5 years (p = 0.715) (n = 50); both groups were 56% male. Later PET-Braak stage was more frequent in patients with CAA than in HCs (46% vs 18%, p = 0.003). However, in multivariable models, later PET-Braak stage was independently associated with age (odds ratio [OR] 1.19, 95% CI 1.07-1.35, p < 0.001) and PiB uptake (OR 1.72, 95% CI 1.32-2.26, p < 0.001), but not with CAA diagnosis (p = 0.264). Within the CAA cohort, later PET-Braak stage was again independently associated with higher amyloid burden (OR 1.78, 95% CI 1.16-2.73, p = 0.008) but showed no relationship with CAA-related imaging markers or cognitive scores (all p > 0.2).

DISCUSSION: Our results suggest that tau extent is mainly driven by age and vascular amyloid among patients with CAA and that tau extent is not related to CAA-related imaging markers or cognitive scores. These findings further support the view that tau does not affect CAA-specific disease mechanisms among patients with CAA without cognitive impairment.},
}

Humans
Male
Female
Aged
*tau Proteins/metabolism
*Cerebral Amyloid Angiopathy/diagnostic imaging/metabolism/psychology/complications
Cross-Sectional Studies
Positron-Emission Tomography
Magnetic Resonance Imaging
Middle Aged
Aniline Compounds
Cognitive Dysfunction/diagnostic imaging/metabolism
Aged, 80 and over
*Brain/diagnostic imaging/metabolism
Carbolines
Thiazoles
Neuropsychological Tests

@article {pmid41945905,
year = {2026},
author = {Justo-Henriques, SI and Padeiro, M and Silva, RCG and Macedo, J and Borges-Machado, F and São João, RMV and Ribeiro, O},
title = {Digital and Analogical Cognitive Stimulation in Older Adults with Alzheimer's Disease: A Multicenter Randomized Controlled Trial Study Protocol.},
journal = {Acta medica portuguesa},
volume = {39},
number = {4},
pages = {281-286},
doi = {10.20344/amp.24360},
pmid = {41945905},
issn = {1646-0758},
mesh = {Humans ; *Alzheimer Disease/therapy/psychology ; Quality of Life ; Aged ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; *Cognitive Behavioral Therapy/methods ; Cognition ; Male ; Female ; },
abstract = {The growing incidence of neurodegenerative diseases in older adults, with the prevalence of Alzheimer's disease, progressively affects their quality of life. Cognitive stimulation is a psychosocial intervention that has shown consistent benefits in the lives of people with dementia from mild to moderate stages. The present study aims to evaluate the effectiveness of digital and analogical cognitive stimulation, when compared with usual care, on overall cognitive function, emotional state, and quality of life. It also aims to investigate whether institutional and territorial characteristics of social care services moderate these effects. This is a three-arm multicenter randomized controlled trial with repeated measures (pre-intervention, post-intervention, and follow-up). The intervention consists of 24 individually applied (digital and analogical) cognitive stimulation sessions, twice a week, for 12 weeks, in two intervention groups. The control group receives usual care. The study follows the recommendations of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2025), including the extension for non-pharmacological interventions. The sample size is estimated at 222 older adults with a probable diagnosis of mild to moderate Alzheimer's disease. Sociodemographic, social, health and clinical data, as well as information on care provider institutions, will be collected and analyzed. Outcomes include cognition (global cognition, memory, and executive function), emotional state (anxiety and depression), and quality of life. All outcomes will be assessed at baseline, endpoint, and follow-up, with comparisons between the intervention groups and the control group.},
}

Humans
*Alzheimer Disease/therapy/psychology
Quality of Life
Aged
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
*Cognitive Behavioral Therapy/methods
Cognition
Male
Female

@article {pmid41946054,
year = {2026},
author = {Tang, S and Peng, Y and Li, Y and Li, Y and Sun, H and Piao, S and Liu, Z and Wu, Y and Hou, Z and Liu, Z and Liu, S and Wang, R},
title = {Congming decoction alleviates Alzheimer's Disease induced by Aβ25-35 in rats via the microbiota-metabolism-inflammation axis, demonstrating its formulation advantages.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {155},
number = {},
pages = {158139},
doi = {10.1016/j.phymed.2026.158139},
pmid = {41946054},
issn = {1618-095X},
abstract = {BACKGROUND: Congming decoction (CMD) is a traditional Chinese herbal formulation traditionally employed for enhancing memory. Despite its historical use, the specific mechanisms and advantages of CMD in the context of Alzheimer's disease (AD) remain inadequately understood.

PURPOSE: This study seeks to elucidate the therapeutic effects of CMD on AD in rats induced by Aβ25-35 and to clarify its underlying process through a multi-perspective approach.

STUDY DESIGN AND METHODS: Cognitive function and pathological alterations were assessed using behavioral tests, hematoxylin and eosin (HE) staining, and immunohistochemistry. Fecal metabolomics analysis, conducted via ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS), was utilized to investigate CMD's impact on metabolic disorders. The structure of the gut microbiota was analyzed through 16S rRNA sequencing. Short-chain fatty acids (SCFAs) and bile acids (BAs) in feces, serum, and brain tissue were quantified using gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-TQ-MS). To establish causal relationships, experiments involving antibiotic-induced microbiota depletion (ABX) and fecal microbiota transplantation (FMT) were performed. Network pharmacology and molecular docking techniques were also employed to identify potential active components and targets. Inflammatory markers were evaluated using enzyme-linked immunosorbent assay (ELISA) kits, immunohistochemistry, and immunofluorescence in brain tissue.

RESULTS: CMD markedly enhanced learning and memory, mitigated pathological changes in the brain and colon, and reestablished gut microbiota equilibrium. It regulated 45 endogenous metabolites involved in BAs, α-linolenic acid, and linoleic acid metabolism. CMD also modulated the levels of SCFAs and BAs in fecal matter, serum, and brain tissue. Strong correlations were identified among gut microbiota, metabolites, and AD-related indicators. Antibiotic treatment inhibited the neuroprotective benefits of CMD, whereas FMT from CMD-treated donors successfully replicated its therapeutic benefits. Network pharmacology analysis indicated that the active components of CMD might target inflammatory pathways. Additionally, CMD exhibited a significant restorative impact on markers associated with the AKT/NF-κB signaling pathway.

CONCLUSION: CMD exerts anti-AD effects by modulating the microbiota-gut-brain axis through remodeling gut microbiota, regulating metabolic homeostasis, and reducing brain inflammation. Notably, CMD demonstrated superior efficacy compared to single herbs or herb pairs.},
}

@article {pmid41946261,
year = {2026},
author = {Zhu, Y and Lan, G and Li, A and Zhang, L and Jiang, M and Yang, J and Zhu, J and He, Z and Zhou, X and Li, M and Wang, Y and Sun, P and Cai, Y and Liu, Z and Wang, YJ and Han, Y and Bu, G and Guo, T},
title = {Association of plasma glial fibrillary acidic protein and APOE-ε4 with Alzheimer's disease.},
journal = {Neurobiology of aging},
volume = {164},
number = {},
pages = {19-27},
doi = {10.1016/j.neurobiolaging.2026.03.009},
pmid = {41946261},
issn = {1558-1497},
abstract = {Both Apolipoprotein E-ε4 (APOE-ε4) and astrocytic activation, as measured by glial fibrillary acidic protein (GFAP), play critical roles in Alzheimer's disease (AD). However, the influence of astrocytic activation on the relationship between APOE-ε4 and AD pathologies remains unclear. This study investigates the interrelationships among astrocytic activation, APOE-ε4, and AD pathophysiology in 529 participants who underwent plasma biomarker measurements, APOE genotyping, and cognitive testing. Additionally, 277, 284, and 104 underwent structural magnetic resonance imaging (MRI), amyloid-β (Aβ) positron emission tomography (PET), and tau PET, respectively. The associations of plasma GFAP, APOE-ε4, and AD-related biomarkers, as well as whether plasma GFAP mediates APOE-ε4-related effects on AD, were investigated. Higher plasma GFAP and APOE-ε4 were independently associated with more severe Aβ and tau aggregation, as well as cognitive decline. Mediation analyses showed a significant indirect effect of APOE-ε4 on plasma p-tau biomarkers (21.1%-24.9%), Aβ PET (16.4%), and cognition (19.6%), while the indirect effect on tau PET was trend-level (29.1%, pFDR = 0.051). These findings highlight the central role of astrocytic activation in AD pathogenesis and underscore plasma GFAP as a promising biomarker for risk stratification and therapeutic targeting.},
}

@article {pmid41946658,
year = {2026},
author = {Merlino, L and Rainone, F and Tollitt, J and Kalra, MJ and Williford, S and Rusconi, F and Battini, GG and Dunne, RA and Hackett, G and Kalra, PA},
title = {Safety of Testosterone Therapy in Chronic Kidney Disease: A Propensity Score-Matched Cohort Study.},
journal = {The world journal of men's health},
volume = {},
number = {},
pages = {},
doi = {10.5534/wjmh.250333},
pmid = {41946658},
issn = {2287-4208},
abstract = {PURPOSE: Testosterone deficiency is highly prevalent in men with chronic kidney disease (CKD) and contributes to frailty, fatigue, and cognitive decline. While testosterone replacement therapy (TRT) may alleviate these complications, concerns persist regarding its cardiovascular and oncologic safety in CKD. Evidence specific to this population is lacking.

MATERIALS AND METHODS: We performed a retrospective, propensity score-matched cohort study using the TriNetX Global Collaborative Network. Male patients aged 18-80 years with CKD stages 3-5 and hypogonadism were included. Patients were stratified by TRT exposure within six months of diagnosis. Exclusions were prior transplantation, eGFR <10 mL/min/1.73 m², dialysis or dementia occurring within one month of CKD. Outcomes over five years included all-cause mortality (primary outcome), vascular dementia, Alzheimer's disease, stroke, myocardial infarction, heart failure, and prostate cancer. Propensity score matching (1:1) balanced demographics, comorbidities, and laboratory measures. Cox proportional hazards models estimated hazard ratios (HRs).

RESULTS: After matching, 1,545 patients were included in each of the two cohorts (TRT treated or non-treated) with well-balanced characteristics (mean eGFR 47.7±15.1 mL/min/1.73 m²). Median follow-up was 3.7 years. All-cause mortality was lower in the TRT group (HR 0.78, 95% confidence interval 0.63-0.98). No significant differences were observed for cardiovascular outcomes, prostate cancer or dementia.

CONCLUSIONS: In men with CKD and hypogonadism, TRT was associated with improved survival and no excess risk of cardiovascular events, prostate malignancy or dementia. These findings suggest TRT is a safe therapeutic option in this high-risk population, warranting further prospective evaluation.},
}

@article {pmid41946675,
year = {2026},
author = {González, KA and Tarraf, W and Banks, SJ and Bangen, KJ and Pa, J and Gallo, LC and Stickel, AM and Filigrana, P and Isasi, CR and Daviglus, M and Testai, FD and Lamar, M and DeCarli, C and González, HM},
title = {Diabetes, hyperglycemia, and brain MRI biomarkers: results from SOL-INCA MRI study.},
journal = {Nutrition & diabetes},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41387-026-00415-z},
pmid = {41946675},
issn = {2044-4052},
support = {R01AG075758-02//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; },
abstract = {OBJECTIVE: Hispanic/Latino individuals have higher rates of type 2 diabetes and Alzheimer's Disease and Related Dementia (ADRD) burden compared to non-Hispanic whites. Diabetes is a risk factor for ADRD, but the extent of its associations with brain markers in community-dwelling Hispanic/Latino individuals is unknown. We examined how glycemic dysregulation and diabetes associate with small vessel disease damage and neurodegeneration in Hispanic/Latino adults from a large and community-representative cohort study.

RESEARCH DESIGN AND METHODS: We used data from 2627 individuals, aged 35-85 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) who underwent brain imaging through the SOL/Investigations of Neurocognitive Aging MRI (SOL-INCA MRI; 2018-2022) study. Exposures included diabetes status and HbA1c (%) levels. Outcomes included white matter hyperintensities, free water, fractional anisotropy, and volumetric regions including hippocampus, lateral ventricles, total brain, and cortical gray matter.

RESULTS: Diabetes status, compared to no diabetes, was associated with larger white matter hyperintensity volume, lower fractional anisotropy, and higher free water. Diabetes status was also associated with larger lateral ventricles as well as smaller total brain, frontal gray matter, and occipital gray matter volumes. The association between diabetes and brain MRI outcomes was stronger in middle-aged and older individuals (50 years and older) compared to younger individuals (35-49 years).

CONCLUSION: Diabetes was associated with markers of small vessel disease (white matter micro and macrostructural damage) and neurodegeneration (smaller brain volumes). White matter hyperintensities have been associated with increased risk of stroke and cognitive decline. Other work has found that free water and fractional anisotropy may predict worse cognitive performance, even in normal-appearing white matter. Smaller brain volumes have also been associated with cognitive deficits. These findings highlight the additional ADRD burden this population faces due to their higher diabetes prevalence.},
}

@article {pmid41946684,
year = {2026},
author = {Pedrolli, F and Morello, G and Gesmundo, I and Banfi, D and Ferro, A and Wangpaichitr, M and Sha, W and Tamagno, E and Schally, AV and Guglielmotto, M and Granata, R},
title = {Growth hormone-releasing hormone attenuates amyloid deposition and neuroinflammation in Alzheimer's disease models.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08699-w},
pmid = {41946684},
issn = {2041-4889},
support = {20223WSTY4//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 202229X8hW//Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)/ ; 106459/2023.1741//Fondazione CRT (CRT Foundation)/ ; 10683/2023.1759//Fondazione CRT (CRT Foundation)/ ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau hyperphosphorylation, neuroinflammation, and synaptic loss. Existing therapies provide only modest symptomatic relief and fail to slow disease progression. Beyond its role in promoting pituitary growth hormone (GH) secretion, growth hormone-releasing hormone (GHRH) has shown neuroprotective effects in experimental ischemic stroke and spinal muscular atrophy. Here, we explored the therapeutic potential of GHRH and its agonist MR-409 in AD models. In vitro, GHRH(1-44)NH2 promoted survival, proliferation, and neuronal differentiation of rat hippocampal neural stem cells (NSCs) and human SH-SY5Y neuroblastoma cells under growth factor deprivation and amyloid beta (Aβ)1-42 exposure. These effects involved the cAMP/PKA/CREB, ERK1/2, and PI3K/Akt signaling pathways. GHRH also attenuated Aβ-induced neurotoxicity by reducing apoptosis, suppressing GSK-3β activity and tau phosphorylation, restoring nuclear β-catenin, and inhibiting NF-κB-mediated inflammation. In vivo, subcutaneous administration of MR-409 in 5xFAD mice reduced Aβ deposition, tau phosphorylation, gliosis, and proinflammatory cytokine expression. In addition, MR-409 mitigated neuronal and synaptic loss, activated survival and neurogenic pathways, and improved cognitive performance, without altering systemic GH and IGF1 levels. MR-409 also elevated NRF2 mRNA expression while reducing its negative regulator KEAP1. Overall, these findings indicate that GHRH and its analog MR-409 exert neuroprotective effects by modulating key pathological features of AD, including neurodegeneration, impaired neurogenesis, neuroinflammation, and oxidative stress. Given their ability to modulate multiple pathological pathways, GHRH agonists may represent promising therapeutic candidates for AD and other neurodegenerative disorders.},
}

@article {pmid41946775,
year = {2026},
author = {Phemphunananchai, K and Waiwut, P and Phetcharaburanin, J and Poonsawas, P and Boonyarat, C},
title = {Repurposing FDA-approved drugs as multi-target neuroprotective agents for Alzheimer's disease via computational screening and experimental validation.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-46708-2},
pmid = {41946775},
issn = {2045-2322},
support = {67-2(7)/2567//Faculty of Pharmaceutical Sciences, Khon Kaen University, Thailand/ ; RA2567-M109//The Research Assistant Program, Khon Kaen University, Thailand/ ; },
}

@article {pmid41936903,
year = {2026},
author = {Senkowska, Z and Weglarz-Tomczak, E},
title = {Decoding the Secretase Puzzle in Amyloid-β Generation: A State-of-the-Art Overview of the Protease-Mediated APP Processing Cascade in Alzheimer's Disease.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103116},
doi = {10.1016/j.arr.2026.103116},
pmid = {41936903},
issn = {1872-9649},
abstract = {The accumulation of amyloid β (Aβ) protein in the brain is a central pathological hallmark of Alzheimer's disease (AD). This process has become a major focus of interdisciplinary research and a critical target in drug development. Aβ is produced through the proteolytic processing of amyloid precursor protein (APP) by a group of enzymes known as secretases. They belong to different protease classes and operate through proteolytic cleavage of the peptide bond through several catalytic hydrolysis. Dysregulation of the expression or/and activity of proteases involved in APP processing disrupts the balance between the amyloidogenic and non-amyloidogenic pathways-often shifting it toward the amyloidogenic route. This shift leads to excessive production and further aggregation of Aβ peptides, ultimately resulting in neuronal toxicity. In this review, we integrate current state-of-the-art knowledge on all proteases reported to cleave APP, encompassing both canonical and non-canonical pathways, and offer detailed examination of cleavage-site topology, and catalytic mechanisms. By integrating the spatial and sequential hierarchy of APP proteolysis across cellular compartments, we establish a unifying mechanistic framework that captures the complexity of the process. We further delineate how distinct proteases-through defined active-site architectures, conserved catalytic motifs, and nucleophile-driven peptide bond hydrolysis-precisely regulate APP processing. This mechanistic perspective advances our molecular understanding of A pathogenesis and delineates critical catalytic control nodes amenable to therapeutic intervention. By defining these targets at a mechanistic level, it establishes a rational framework for precision drug design and the development of next-generation therapeutics.},
}

@article {pmid41936993,
year = {2026},
author = {Lizard, G and Sassi, K and Mackrill, JJ and Ghzaiel, I and Meziane, S and Hassen, E and Abdelkarim, M and Masmoudi-Kouki, O and Ghrairi, T and Brahmi, F and Gargouri, A and Rezig, L and Benkalifa, R and Khallouki, F and El Midaoui, A and Pincemail, J and Atanasov, AG and Vejux, A and Millot, N},
title = {7-ketocholesterol as a theranostic target: potential applications and future perspectives.},
journal = {Chemistry and physics of lipids},
volume = {},
number = {},
pages = {105588},
doi = {10.1016/j.chemphyslip.2026.105588},
pmid = {41936993},
issn = {1873-2941},
abstract = {7-Ketocholesterol (7KC) is mainly formed by cholesterol autoxidation and is a pro-oxidant and pro-inflammatory bioactive lipid that also induces different types of cell death, including oxiapoptophagy. It is frequently associated with major age-related diseases, such as cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease. 7KC can therefore be considered a biomarker for these diseases, offering the possibility of developing theranostic strategies combining diagnosis and treatment. Currently, all the elements are in place to develop tools for the design of theranostic therapies targeting 7KC in diseased organs: antibodies, nanoparticles used as nanoplatforms, molecules that neutralize 7KC such as enzymes which degrade it, as well as natural or synthetic compounds that inhibit the cytotoxic signaling pathways associated with oxidative stress, inflammation and cell death activated by 7KC. Identifying and neutralizing 7KC biological activities using a theranostic approach could also be of interest for growing medical fields such as space medicine widely concerned by oxidative stress, aging and age-related diseases, driven by microgravity. This review supports that most of key tools are now available to develop theranostic treatments targeting 7KC in age-related pathologies, especially in cardiovascular diseases associated with atheroma, but also in age-related macular degeneration and Alzheimer's disease. Discovery of effective treatments for these diseases is a major challenge and will answer an important need for both patients and caregivers.},
}

@article {pmid41937092,
year = {2026},
author = {Baldasso, GM and Paes, RS and Moreira, AG and Salvadori, SG and Limberger, C and Roviezzo, F and Capasso, R and Dutra, RC},
title = {The role of cannabinoid ligands in neurodegenerative diseases: emerging anti-inflammatory, immunomodulation and disease-modifying perspectives.},
journal = {Pharmacological research},
volume = {},
number = {},
pages = {108185},
doi = {10.1016/j.phrs.2026.108185},
pmid = {41937092},
issn = {1096-1186},
abstract = {Neurodegenerative diseases (NDs) constitute a growing global health burden driven by population aging and remain without disease-modifying therapies. Although chronic neuroinflammation and aberrant protein aggregation are widely recognized as shared pathological hallmarks of major NDs - including Alzheimer's, Parkinson's, Huntington's diseases and multiple sclerosis - the causal relationships linking immunoinflammatory signaling to neurodegenerative progression remain contentious. Therapeutic strategies targeting neuroinflammation have thus far yielded limited clinical success, underscoring the need for mechanistically grounded and context-specific interventions. The endocannabinoid system (ECS) is a key regulator of synaptic function, glial activity, and immune homeostasis in the central nervous system (CNS), and its dysregulation has been consistently reported in neurodegenerative settings. However, ECS alterations across NDs are heterogeneous and often disease- and stage-dependent, with conflicting findings regarding cannabinoid receptor expression, endocannabinoid tone, and functional outcomes. Moreover, while preclinical studies demonstrate robust anti-inflammatory and neuroprotective effects of cannabinoid ligands, clinical translation has been constrained by issues of receptor specificity, psychoactive side effects, limited brain penetration, and an incomplete understanding of long-term ECS modulation. In this Review, we critically evaluate current evidence linking ECS signaling to neuroinflammatory mechanisms in neurodegeneration, highlighting both convergent pathways and unresolved controversies. We discuss the translational implications of ECS-targeted strategies, including the development of selective receptor modulators, allosteric and/or bitopic/dualsteric ligands, and enzyme inhibitors, as well as emerging approaches to mitigate adverse effects and improve therapeutic precision. By integrating mechanistic insights with clinical challenges, this Review delineates key obstacles and opportunities for advancing ECS-based interventions toward disease-modifying therapies for neurodegenerative disorders.},
}

@article {pmid41937403,
year = {2026},
author = {Borda, MG and O'Hara-Veintimilla, K and Aarsland, D},
title = {Older Adults, Anti-Amyloid Therapy, and Frailty: What Oncology Can Teach Us.},
journal = {European journal of neurology},
volume = {33},
number = {4},
pages = {e70567},
doi = {10.1111/ene.70567},
pmid = {41937403},
issn = {1468-1331},
support = {//Helse Vest/ ; //Nasjonalforeningen for Folkehelsen/ ; },
mesh = {Humans ; *Frailty/diagnosis ; Aged ; *Geriatric Assessment/methods ; *Alzheimer Disease/drug therapy ; *Medical Oncology/methods ; Clinical Decision-Making ; Frail Elderly ; },
abstract = {BACKGROUND: Anti-amyloid therapies, such as lecanemab or donanemab, represent the first disease-modifying treatments approved for early Alzheimer's disease (AD) in individuals with confirmed amyloid pathology. Their implementation in routine care raises important challenges, particularly in older adults with heterogeneous functional reserve and multimorbidity. We address the role of frailty in refining clinical decision-making for anti-amyloid therapies.

METHODS: This short communication presents a conceptual discussion informed by geriatric oncology, where frailty assessment and comprehensive geriatric assessment (CGA) are routinely used to individualize treatment in heterogeneous older populations. We describe how similar principles may be applied to anti-amyloid monoclonal antibodies once regulatory eligibility has been established, and outline a frailty-informed conceptual framework to support clinical decision-making in routine care.

RESULTS: This conceptual analysis proposes a stepwise, frailty-informed clinical framework that integrates regulatory eligibility assessment with brief frailty screening and targeted comprehensive geriatric assessment. The framework defines differentiated clinical pathways for robust, pre-frail, and frail individuals, linking frailty status to specific decisions regarding treatment initiation, need for prehabilitation, intensity of monitoring, and consideration of treatment deferral. By embedding frailty assessment within routine clinical workflows, the framework operationalizes evaluation of physiological reserve, anticipates treatment burden and monitoring feasibility, and provides a structured approach to individualized risk-benefit appraisal for anti-amyloid therapies.

CONCLUSIONS: Frailty-informed frameworks may offer a pragmatic and ethically grounded approach to support real-world implementation of anti-amyloid therapies, guiding treatment selection as well as longitudinal decisions on monitoring, continuation, and reassessment over time.},
}

Humans
*Frailty/diagnosis
Aged
*Geriatric Assessment/methods
*Alzheimer Disease/drug therapy
*Medical Oncology/methods
Clinical Decision-Making
Frail Elderly

@article {pmid41937689,
year = {2026},
author = {Helphrey, JH and Hart, J and McClintock, SM and Peters, ME and Thakkar, VJ and LoBue, C},
title = {A scoping review of frontal cortex tDCS on neuropsychological functioning in older adults with mild cognitive impairment and Alzheimer's Clinical Syndrome.},
journal = {International review of psychiatry (Abingdon, England)},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/09540261.2026.2647921},
pmid = {41937689},
issn = {1369-1627},
abstract = {Mild cognitive impairment (MCI) and Alzheimer's Clinical Syndrome (ACS) are prevalent, incurable, and are expected to increase in incidence over the next 30 years. Finding new treatments to address the cognitive and behavioral problems in MCI and ACS represent an urgent need. Brain circuitry disruption can cause cognitive dysfunction and neuropsychiatric symptoms (NPS) in both MCI and ACS. Therefore, one promising avenue of treatment is non-invasive brain stimulation through transcranial direct current stimulation (tDCS). This scoping review examined the current knowledge base for the potential neuropsychological and neuropsychiatric effects of frontal cortex tDCS in older adults with MCI and ACS. Of the 17 randomized controlled trials reviewed, treatment parameters such as session length, current intensity, number of treatments, and time between treatments varied widely across studies, which restricted identification of optimal tDCS treatment protocols. Mixed findings on neuropsychological outcomes were observed, though significant improvements were most commonly seen in studies measuring global cognition (10) followed by executive function (6). Only three studies yielded clinically significant cognitive improvement, and few studies assessed NPS outcomes. Additional rigorous research is indicated to enhance our understanding of tDCS as a treatment for cognitive and neuropsychiatric symptoms in older adults with MCI and ACS.},
}

@article {pmid41937703,
year = {2026},
author = {Salim, MW and Zhang, W and Collins-Praino, L and Wang, Y and Care, A},
title = {Small Extracellular Vesicles from Neural Cells: Physiological and Pathological Roles, and Potential in Neurodegenerative Therapy.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e04608},
doi = {10.1002/adhm.202504608},
pmid = {41937703},
issn = {2192-2659},
support = {//Higher Education Commission/ ; //International Macquarie University Research Excellence Scholarship/ ; FT210100737//ARC Future Fellowship/ ; //Dementia Australia Research Foundation/ ; //Mason Foundation/ ; //National Foundation for Medical Research & Innovation/ ; },
abstract = {Small extracellular vesicles (sEVs) have emerged as central mediators of intercellular communication in the central nervous system (CNS) and are increasingly recognized for their dual roles in the pathogenesis and treatment of neurodegenerative diseases (NDDs). In disease contexts, sEVs facilitate the intercellular dissemination of pathogenic proteins and nucleic acids, thereby contributing to the propagation of Alzheimer's disease (AD) and Parkinson's disease (PD) pathology. Conversely, their intrinsic biocompatibility, capacity to traverse brain barriers, and inherent organotropic properties position sEVs as highly promising nanocarriers for CNS drug delivery. While mesenchymal stem cell-derived sEVs have been widely investigated in preclinical NDD models, accumulating evidence suggests that sEVs derived from neural cells, including neural stem cells, neurons, astrocytes, microglia, oligodendrocytes, and brain endothelial cells may offer superior brain targeting, disease relevance, and functional efficacy. This review provides a comprehensive and critical analysis of current knowledge on neural cell-derived sEVs, encompassing their physiological roles in brain homeostasis, their involvement in AD and PD pathogenesis, and their emerging therapeutic applications. We discuss cell-type-specific sEV cargo profiles, mechanisms underlying blood-brain and blood-cerebrospinal fluid barrier traversal, and recent advances in endogenous and exogenous engineering strategies that enhance cargo loading, targeting precision, and therapeutic performance. Importantly, we address key translational challenges that currently limit clinical implementation. By integrating mechanistic insights with therapeutic and engineering perspectives, this review highlights neural cell-derived sEVs as a biologically informed and versatile platform, underscoring their potential to advance next-generation neuro-nanomedicine for NDDs.},
}

@article {pmid41937809,
year = {2026},
author = {Mehmood, A and Farman, M and Afzal, F and Nisar, KS and Ahmed, MA and Hafez, M},
title = {Correction: A Physics Informed Neural Network (PINN) framework for fractional order modeling of Alzheimer's disease.},
journal = {Frontiers in neuroinformatics},
volume = {20},
number = {},
pages = {1821637},
doi = {10.3389/fninf.2026.1821637},
pmid = {41937809},
issn = {1662-5196},
abstract = {[This corrects the article DOI: 10.3389/fninf.2026.1748481.].},
}

@article {pmid41938067,
year = {2026},
author = {Cao, H and Liang, J and Dong, X and Xia, Z and Luo, X and Liu, B},
title = {Protein lactylation in Alzheimer's disease: bridging metabolism, pathology, and therapeutic opportunity.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1790090},
pmid = {41938067},
issn = {1663-4365},
abstract = {Lactate, long regarded as a mere by-product of glycolysis, is increasingly recognized as a signaling metabolite and epigenetic regulator through protein lactylation. This lysine-specific post-translational modification functionally couples cellular metabolic states to gene regulatory programs and orchestrates cell type-specific functions across neurons, astrocytes, and microglia, thereby shaping synaptic plasticity, neuroinflammatory responses, and protein aggregation. Accumulating evidence implicates dysregulated lactylation in the pathogenesis of Alzheimer's disease (AD), where it modulates amyloid-β deposition, tau aggregation, and glial reactivity. In this Review, we summarize the enzymatic regulation of protein lactylation, delineate its context-dependent roles in distinct central nervous system cell types, and highlight its function as a metabolic-epigenetic-immune nexus in AD progression. We further discuss emerging therapeutic strategies targeting lactate metabolism and lactylation pathways, and outline critical knowledge gaps that must be addressed to translate these insights into innovative diagnostic and therapeutic approaches. By integrating metabolic reprogramming, epigenetic control, and cell-specific mechanisms, this Review positions lactylation as a compelling and emerging frontier in AD research.},
}

@article {pmid41938070,
year = {2026},
author = {Samokhina, E and Buskila, Y},
title = {Astrocytic K[+] regulation during neurodegenerative diseases.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1782460},
pmid = {41938070},
issn = {1663-4365},
abstract = {Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in specific areas of the central nervous system. Historically, a "neurocentric" paradigm viewed glial cells, such as astrocytes, as cells that provided adequate support for neuronal energy metabolism and controlled local cerebral blood flow. However, studies from the past two decades found that astrocytes are involved in synaptic function through different mechanisms, including the uptake of extracellular glutamate molecules and potassium ions following synaptic neuronal transmission. Also, astrocytes respond to neurotransmitters and neuromodulators through alterations of intracellular ion concentrations (e.g., Na[+], Ca[2+], K[+]) and the release of gliotransmitters. Astrocytes play a pivotal role in preserving potassium homeostasis within the central nervous system through their potassium channels, a process known as "potassium clearance." Impaired astrocytic potassium clearance mechanisms can result in neuronal hyperexcitability, leading to increased glutamate release, overactivation of glutamate receptors, and cytotoxicity. Recent studies suggest that these factors can cause cell death and neurodegeneration, and further indicate a region-specific glial dysfunction in neurodegeneration, which reflects the heterogeneity of glial cell function and sensitivity across different brain regions. Overall, this manuscript offers novel insights into a relatively new concept that glial cells can actively shape neuronal activity and survival.},
}

@article {pmid41938171,
year = {2026},
author = {He, Y and Qu, M and Yu, L and He, L and Lu, Y and Hong, J and Sun, M and Yang, H and Mi, W and Guo, H and Ma, Y},
title = {Blood-Brain Barrier: Structure, Function, Diseases, and Drug Delivery Systems.},
journal = {MedComm},
volume = {7},
number = {4},
pages = {e70712},
pmid = {41938171},
issn = {2688-2663},
abstract = {The blood-brain barrier (BBB) is a highly selective and dynamic neurovascular interface essential for maintaining central nervous system homeostasis. This specialized barrier comprises brain microvascular endothelial cells interconnected by tight junctions, supported by pericytes and astrocytic end-feet within the neurovascular unit. While protecting the brain from circulating pathogens and toxins, the BBB presents formidable obstacles to drug delivery, restricting approximately 98% of small-molecule therapeutics and nearly all large biomolecules from reaching the brain parenchyma. BBB dysfunction is critically implicated in the pathogenesis and progression of numerous neurological disorders, including ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and brain tumors. This comprehensive review systematically examines the structural organization and functional characteristics of the BBB, elucidates its pathophysiological roles across major neurological diseases, and critically evaluates innovative drug delivery strategies designed to overcome this biological barrier. We analyze passive targeting approaches, active targeting mechanisms via receptor-mediated transcytosis, and stimuli-responsive systems including focused ultrasound and magnetic guidance. Additionally, we discuss multifunctional nanoplatforms, biomimetic cell membrane-coated delivery systems, current preclinical evidence, and clinical translation challenges. Finally, we propose future research directions and identify specific experimental pathways to accelerate the development of next-generation BBB-targeted therapeutics from preclinical promise to clinical application.},
}

@article {pmid41938337,
year = {2026},
author = {Saranya, K and Joseph, ER and Kalaiarasi, T and Karthiga, M},
title = {Generative AI in drug repurposing and biomarker discovery: a multimodal approach.},
journal = {Frontiers in bioinformatics},
volume = {6},
number = {},
pages = {1755412},
pmid = {41938337},
issn = {2673-7647},
abstract = {INTRODUCTION: Computational drug repurposing has been widely explored using similarity-based methods, network diffusion, matrix factorization, deep learning, and graph neural networks (GNNs). However, recent heterogeneous GNN models, such as TxGNN and GAT-based models, demonstrate serious limitations for real-world biomedical applications, including poor generalization to sparsely annotated diseases, limited disease-level adaptation, and inability to effectively combine heterogeneous evidence from curated databases, multi-omics profiles, and unstructured biomedical literature.

METHODS: This article proposes a heterogeneous attention-based meta-learning graph neural network named HAMGNN, which employs three major innovations: (i) relation-sensitive multi-head attention to prioritize biologically significant interactions among heterogeneous edge types, (ii) a disease-focused meta-learning framework enabling rapid adaptation to newly observed or under-informed diseases, and (iii) a literature-enhanced knowledge graph construction pipeline encoding high-confidence, LLM-extracted therapeutic information. The model was tested on a large multimodal biomedical knowledge graph assembled from DrugBank, DisGeNET, and Hetionet, comprising more than 2.2 million edges, using a stringent disjoint disease-based (cold-start) evaluation protocol.

RESULTS: HAMGNN achieved a receiver operating characteristic-area under the curve (ROC-AUC) of 0.98 and precision of 0.95, representing a 10%-15% improvement over TxGNN and GAT-GNN on unseen disease generalization. Translational applicability was demonstrated through Alzheimer's disease and Long COVID case studies, identifying clinically plausible repurposing candidates and disease-associated biomarker signatures via mechanistic pathways.

DISCUSSION: HAMGNN offers a generalized, biologically grounded, and unified framework for evidence-based drug repurposing and biomarker discovery in complex and emerging diseases.},
}

@article {pmid41938524,
year = {2026},
author = {Raj, N and R, SP and Ammar, RB and Rajendran, P and Chellappan, BV},
title = {Non-Coding DNA-Derived Mimotopes of Aβ42 as Novel Candidates for Alzheimer's Peptide Vaccine Design.},
journal = {International journal of medical sciences},
volume = {23},
number = {4},
pages = {1320-1332},
pmid = {41938524},
issn = {1449-1907},
mesh = {*Amyloid beta-Peptides/immunology/chemistry/genetics ; *Alzheimer Disease/immunology/therapy/prevention & control/genetics ; Humans ; *Peptide Fragments/immunology/chemistry/genetics ; *Vaccines, Subunit/immunology ; Epitopes, B-Lymphocyte/immunology/genetics/chemistry ; *Alzheimer Vaccines/immunology ; Molecular Docking Simulation ; Peptide Library ; Protein Subunit Vaccines ; },
abstract = {Alzheimer's disease (AD), the leading cause of dementia, is a progressive neurodegenerative disorder marked by memory loss, cognitive decline, and characteristic neuropathology involving amyloid-β (Aβ) plaques and tau tangles. Among emerging therapeutic strategies, Aβ-targeted immunotherapy using monoclonal antibodies or peptide vaccines offers the most promising disease-modifying potential. Mimotopes, short peptides that mimic antigenic epitopes of Aβ, have recently gained attention as safe and effective candidates for vaccine development. In this study, we employed a computational immunoinformatics approach to identify novel Aβ42-mimicking peptides derived from non-coding DNA sequences, representing an unconventional yet rich source of bioactive peptides. A virtual peptide library was generated from intergenic regions of the Escherichia coli genome and screened using B-cell epitope prediction, MHC-binding analysis, and structural similarity modeling to identify potential immunogenic mimotopes. Selected candidates were further evaluated through peptide-antibody docking with Aβ42-specific antibody fragments to assess binding affinity and epitope mimicry. Our findings demonstrate a novel computational framework for mining non-coding DNA to identify therapeutic peptide mimotopes. The identified Aβ42-like peptides exhibit strong potential as synthetic vaccine candidates for Alzheimer's disease, supporting a new direction in rational vaccine design against neurodegenerative disorders.},
}

*Amyloid beta-Peptides/immunology/chemistry/genetics
*Alzheimer Disease/immunology/therapy/prevention & control/genetics
Humans
*Peptide Fragments/immunology/chemistry/genetics
*Vaccines, Subunit/immunology
Epitopes, B-Lymphocyte/immunology/genetics/chemistry
*Alzheimer Vaccines/immunology
Molecular Docking Simulation
Peptide Library
Protein Subunit Vaccines

@article {pmid41938573,
year = {2026},
author = {Mulligan, MD and Scott, MR and Yang, Q and Wang, R and Ghosh, S and Johnson, KA and Beiser, AS and Seshadri, S and McGrath, ER},
title = {Association of Circulating Vitamin D in Midlife With Increased Tau-PET Burden in Dementia-Free Adults.},
journal = {Neurology open access},
volume = {2},
number = {2},
pages = {},
pmid = {41938573},
issn = {2998-7601},
abstract = {BACKGROUND AND OBJECTIVES: Low circulating vitamin D in later-life has been associated with increased risk of cognitive impairment and clinical dementia. However, whether serum vitamin D in early mid-life is associated with neuroimaging markers of preclinical dementia is unknown. We aimed to determine the association between early mid-life serum vitamin D and subsequent tau- and amyloid- burden on brain-PET, in a cohort of dementia-free adults.

METHODS: This was a prospective cohort study of Framingham Heart Study Generation 3 cohort participants who were dementia-free at time of PET, had serum 25-hydroxyvitamin D [25(OH)D] measured at examination cycle 1 (2002-2005) and had available 11C-Pittsburgh Compound-B (PiB)- and/or 18F-Flortaucipir (FTP)-PET completed between 2016 and 2019. Outcomes included global tau-PET deposition (across all 34 FreeSurfer defined cortical regions), composite tau (those regions most susceptible to early tau involvement in AD dementia, namely entorhinal cortex, parahippocampal gyrus, fusiform gyrus, amygdala and inferior and middle temporal cortices) and amyloid-PET deposition (composite region including the frontal, lateral temporal, parietal and retrosplenial cortices [FLR]). Data were analyzed using multivariable linear regression models adjusted for age, sex, time from blood sampling to PET, PET camera type, depression, season, current smoking, systolic blood pressure, use of antihypertensive medication, diabetes mellitus, cardiovascular disease, and body mass index.

RESULTS: In our sample (n= 793, 53% women, mean age 39±8years) with available serum 25(OH)D and amyloid (n=424) and/or tau-PET (n=369), the mean time between blood sampling and PET was 16±2 years. On multivariable linear regression analysis, higher serum 25(OH)D was associated with lower global (β= -0.022; 95% CI: -0.040 to -0.004; p = 0.010]) and composite tau-PET deposition (β= -0.023; 95% CI: -0.043 to -0.003; p = 0.016]),but was not associated with amyloid-PET burden.

DISCUSSION: In a group of dementia-free individuals, higher serum 25(OH)D at early mid-life was associated with lower tau deposition on brain PET a mean of 16 years later. Low vitamin D in mid-life may represent a potentially modifiable target to mitigate the risk of neuroimaging signs of preclinical dementia.},
}

@article {pmid41938657,
year = {2026},
author = {Clare, L and Gamble, LD and Martyr, A and Knapp, M and Matthews, FE},
title = {Sources of inequality in "living well" with dementia: an intersectional analysis using a British cohort study.},
journal = {Innovation in aging},
volume = {10},
number = {4},
pages = {igag009},
pmid = {41938657},
issn = {2399-5300},
abstract = {BACKGROUND AND OBJECTIVES: A key aim of national dementia policies is to enable people to "live well" with the condition, but the experience of living with dementia, including access to health and social care services, is markedly affected by numerous sources of socioeconomic disparity. We explored how combinations of these disparities among groups of people with dementia are associated with the capability to "live well."

RESEARCH DESIGN AND METHODS: We used baseline data from 1,537 people with mild-to-moderate dementia in the British IDEAL cohort (2014-2016). This included personal characteristics, living situation, socioeconomic position, and geographical area, and 3 indices of "living well"-quality of life, satisfaction with life, and well-being. Through regression-tree analyses, we explored how the intersection of factors beyond type of dementia and co-morbidity is associated with subgroups of people with dementia experiencing higher or lower capability for "living well."

RESULTS: Age, education, living situation, income, and home ownership emerged as the strongest differentiators. Drawing on the concept of precarity, we show how the connections between unequal distribution of resources and personal vulnerabilities lead to an accumulation of pressures and shape outcomes.

DISCUSSION AND IMPLICATIONS: These findings from a cohort of people with dementia in a major Western economy represent the tip of the iceberg relative to the full extent of national and especially global inequalities. Addressing the impact of these social inequalities requires a sustained focus on developing and implementing policies that improve equity of access to care and support and increase the potential for "living well."},
}

@article {pmid41938695,
year = {2026},
author = {Kaur, S and Tyler, AL and Durante, GL and Cary, GA and Carter, GW and Mahoney, JM},
title = {Identifying transcriptomic signatures that mediate the causal effect of genotype on Alzheimer's disease.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1716828},
pmid = {41938695},
issn = {1662-4548},
abstract = {The combined effects of thousands of genetic polymorphisms account for Alzheimer's disease (AD) genetic risk. Most AD polymorphisms affect gene expression. Thus, the transcriptome, the set of all gene expression levels for every gene in the genome, is a major mediator between the genotype to phenotype. This study uses genotypes, transcriptomes, and clinical phenotypes to identify the transcriptomic signature that mediates the causal effect of genotype on AD. By utilizing a causal inference method known as high dimensional mediation analysis (HDMA) on the Religious Orders Study/Memory and Aging Project (ROSMAP) longitudinal cohort, the genotype, transcriptome, and phenotype data were reduced to single scores encoding genotype, transcriptome, and phenotype correlations, and produce a ranked gene list based on putative causal importance of each gene for AD. Analysis of the up- and down-regulated genes prevalent in AD through Gene Ontology (GO) and KEGG databases reveals findings such as up-regulated functions which include angiogenesis and immune responses while down-regulated functions of genes include synaptic activity. Furthermore, utilizing Clue.io to identify candidate drugs to suppress AD-pathology reveals a plausible list of therapeutic candidates, including targeted genes and compounds such as SMAD3, TM7SF2, and ABCB1, which counteract the transcriptomic signature identified and may block the devastating effects of AD related to inflammatory responses, Aβ-induced toxicity, and neuronal death.},
}

@article {pmid41938770,
year = {2026},
author = {Kuang, L and Lei, M and Mu, X and Wang, Y and Li, Y and Xu, H and Li, T and Huang, L and Zheng, Y and Xie, X and Li, C and Fu, W},
title = {Data-independent acquisition quantitative proteomics analysis of milk fat globule membrane proteins in rabbit colostrum and mature milk.},
journal = {Frontiers in veterinary science},
volume = {13},
number = {},
pages = {1703387},
pmid = {41938770},
issn = {2297-1769},
abstract = {Proteomics has been widely used to identify proteins in the milk fat globule membrane (MFGM). However, the characteristics of MFGM proteins in rabbit colostrum (RC) and mature milk (RM) remain largely unexplored. This study aimed to profile the rabbit MFGM proteins and assess differences in component and functional profiles between RC and RM through data-independent acquisition (DIA) quantitative proteomics. We established the proteomic profile of rabbit MFGM, identifying 3,548 proteins across RC and RM. Notably, typical MFGM proteins, such as Perilipin 2 (PLIN2), Xanthine dehydrogenase/oxidase (XDH/XO), and Apolipoprotein, were detected in rabbit milk, and 10 of these were confirmed by Parallel reaction monitoring (PRM) detection. Comparative analysis revealed 480 differentially expressed MFGM proteins (DEMPs), with 379 up-regulated and 101 down-regulated DEMPs in RC compared to RM. This included 68 unique proteins in RC, 5 in RM, and 407 DEMPs expressed in both groups. The GO analysis indicated that DEMPs are predominantly involved in processes such as proteolysis, cell adhesion, and ion transport, with enrichments of 32, 14, and 14 DEMPs, respectively. KEGG analysis gathered 56 significant pathways, most of which were categorized into Human Diseases (20/56) and Metabolism (14/56). Protein-protein interaction (PPI) network analysis emphasized the core role of DEMPs (e.g., proteasome subunits and integrins) in human diseases (e.g., Alzheimer's disease) and in signal transduction (e.g., the PI3K-Akt signaling pathway). These results offer theoretical insights into the components and functions of rabbit milk, suggesting a novel way to enhance the economic benefit of the rabbit industry.},
}

@article {pmid41938851,
year = {2026},
author = {Fan, W and Wang, Z and Wan, S and Liu, M and Han, Y and Liu, X and Xu, L and Wang, X and Zhang, D and Cai, Q},
title = {A study on the correlation between APOE gene polymorphism, white matter hyperintensities, and neuropsychiatric symptom phenotypes in Alzheimer's disease.},
journal = {Frontiers in psychiatry},
volume = {17},
number = {},
pages = {1795598},
pmid = {41938851},
issn = {1664-0640},
abstract = {OBJECTIVE: This study investigates the independent and interactive effects of apolipoprotein E (APOE) genotypes and white matter hyperintensities (WMH) on distinct neuropsychiatric symptom (NPS) phenotypes in patients with Alzheimer's disease (AD).

METHODS: We enrolled 325 AD patients consecutively diagnosed at a specialized memory clinic between May 2024 and May 2025. All participants underwent comprehensive clinical assessments-including the Chinese Mini-Mental State Examination (CMMSE), Activities of Daily Living (ADL) scale, and the Neuropsychiatric Inventory (NPI)-as well as 3T brain MRI for WMH quantification and APOE genotyping. First, we compared NPS profiles and cognitive/functional scores across APOE genotype groups (ϵ2/ϵ2-ϵ2/ϵ3, ϵ3/ϵ3, ϵ3/ϵ4, ϵ4/ϵ4) using analysis of variance (ANOVA) or Kruskal-Wallis tests, as appropriate. Second, we applied mediation analysis (PROCESS macro Model 4, 5,000 bootstrap samples) to examine whether WMH burden mediates the association between APOE genotype (X) and outcomes including CMMSE total score and domain-specific NPS subscores (delusions, agitation, irritability, euphoria).

RESULTS: Significant differences emerged across APOE genotypes in both cognition (CMMSE, p < 0.05) and functional status (ADL, p < 0.05). At the symptom level, carriers of at least one ϵ4 allele exhibited higher agitation scores than non-carriers (p < 0.05); notably, the ϵ4/ϵ4 homozygotes showed significantly greater severity in delusions, agitation, irritability, and euphoria compared with all other genotype groups (all p < 0.05). Mediation analyses revealed no statistically significant indirect effect of APOE genotype on any outcome via WMH, indicating that WMH does not mediate these associations. Instead, APOE genotype exerted robust direct effects on both cognitive performance and specific NPS domains.

CONCLUSION: APOE genotype-particularly the ϵ4/ϵ4 homozygous status-is associated with more pronounced cognitive decline and a distinct, severe NPS profile in AD, especially involving delusions, agitation, Euphoria, and irritability. These associations are independent of WMH burden, suggesting that APOE exerts direct neurobiological effects on neuropsychiatric manifestations. Thus, APOE genotyping holds dual clinical value: not only as a well-established biomarker for AD risk and diagnosis but also as a potential prognostic indicator for behavioral and psychological symptoms-offering actionable insights beyond conventional neuroimaging markers.},
}

@article {pmid41940019,
year = {2026},
author = {Yang, S and Sang, HW and Kim, S and Cho, EJ and Choi, Y and Kang, DW and Jang, YC and Park, DH and Kwak, HB and Yook, JS},
title = {Therapeutic potential of exerkines in neurodegenerative and mental disorders: a narrative review.},
journal = {Frontiers in physiology},
volume = {17},
number = {},
pages = {1793043},
pmid = {41940019},
issn = {1664-042X},
abstract = {Neurodegenerative and mental disorders impose significant global disease burdens and pose serious social and economic challenges. Physical exercise (PE) exerts beneficial effects on brain health, contributing to a reduction in the risk of Alzheimer's disease (AD), Parkinson's disease (PD), depression, anxiety, and post-traumatic stress disorder (PTSD). To understand these effects of PE, a variety of molecules released from various tissues in response to PE have been discovered, which are collectively called 'exerkines'. In particular, the skeletal muscle acts as an endocrine organ, secreting exerkines and is included in the category of myokines that facilitate direct or indirect crosstalk between the muscle and the brain. Although muscles actively interact with organs such as the liver, pancreas, and adipose tissue, the precise mechanisms of muscle-brain communication have yet to be fully elucidated. In the skeletal muscle, the types of exerkines secreted and their effects vary depending on the PE modality. Furthermore, these exerkines can cross the blood-brain barrier (BBB) to exert direct effects or act indirectly via molecular signaling pathways, contributing to the modulation of the brain microenvironment, attenuation of neuroinflammation, and neurodegeneration. Previous studies have indicated that brain-derived neurotrophic factor (BDNF), irisin, cathepsin B (CTSB), interleukin-6 (IL-6), and insulin-like growth factor 1 (IGF-1) are involved in enhancing cognitive performance and improving behavioral outcomes by promoting neurogenesis and synaptic plasticity. This review comprehensively discusses the effects of exerkines on the brain and the physiological responses manifested in neurodegenerative and mental disorders focusing primarily on findings from rodent models. Based on these insights, this review proposes future research directions to translate preclinical findings into therapeutic strategies.},
}

@article {pmid41940185,
year = {2026},
author = {Mukherjee, C and Bajaj, S and Adhikari, BM and Dhamala, M},
title = {Sex-dependent grey matter atrophy in Alzheimer's disease progression.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag103},
pmid = {41940185},
issn = {2632-1297},
abstract = {Alzheimer's disease is a progressive neurodegenerative disorder marked by cognitive and functional deterioration, with mild cognitive impairment as an intermediate stage. Using high-resolution structural MRI from 332 Alzheimer's Disease Neuroimaging Initiative participants, we examined sex-specific grey matter volume (GMV) differences across healthy controls, mild cognitive impairment and Alzheimer's disease. Whole-brain parcellation into 82 regions revealed a significant group-by-sex interaction [F(164,488) = 1.42; P = 0.002; ηp[2] = 0.32], with 10 regions showing pronounced sex-dependent effects. GMV trajectories exhibited a clear sex-specific pattern. In healthy cohort, males and females displayed comparable GMVs. From healthy control to mild cognitive impairment, females remained relatively stable, whereas males showed a moderate decline. From mild cognitive impairment to Alzheimer's disease, however, females demonstrated steep and widespread GMV loss, contrasting with the slower, region-limited atrophy observed in males. Females also showed significantly greater reductions in key regions, including the left frontal pole during Alzheimer's disease progression [F(1,243) = 10.68; P < 0.001; ηp[2] = 0.14] and the right caudal middle frontal cortex during mild cognitive impairment [F(1,243) = 10.62; P < 0.001; ηp[2] = 0.14]. Structural differences were mirrored in behavioural associations. Females showed more widespread associations between GMV and cognitive and functional performance: higher GMV was associated with better Mini-Mental State Examination scores, whereas lower GMV was associated with greater independence on the Functional Activities Questionnaire. These findings highlight a sex-dependent vulnerability in Alzheimer's disease, with females exhibiting both more extensive atrophy and more widespread atrophy-cognition coupling across disease stages.},
}

@article {pmid41940186,
year = {2026},
author = {Hunter, TR and Lyra E Silva, NM and de Freitas, GB and Rody, T and Santos, LE and Zhang, J and Bullock, A and Tartaglia, MC and Abraham, S and Nicolini, C and Nelson, AJ and Heisz, JJ and Fahnestock, M and De Felice, FG},
title = {Fibronectin type III domain-containing protein 5/irisin in extracellular vesicles is reduced in older individuals.},
journal = {Brain communications},
volume = {8},
number = {2},
pages = {fcag085},
pmid = {41940186},
issn = {2632-1297},
abstract = {The progressive accumulation of physiological stress as we age, known as allostatic load, is linked to an increased risk of dementia. Fostering brain resilience through physical exercise can counteract allostatic load and improve adaptation to age-related brain alterations. Fibronectin type III domain-containing protein 5 (FNDC5)/irisin is a neuroprotective exercise-linked hormone found in extracellular vesicles (EV-FNDC5/irisin). Here, we sought to analyse EV-FNDC5/irisin in ageing as a promising biomarker of brain resilience. We measured exercise-associated factors, including EV-FNDC5/irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B in the serum of 31 young (18-28 years) and 19 older subjects (65-79 years). Levels of FNDC5/irisin in serum-derived EVs are markedly reduced in older subjects compared to young (P = 0.004). We report a reduction in nanoparticles isolated from the serum of older participants (P = 0.009). While EV-FNDC5/irisin positively correlates with BDNF in young subjects (Spearman r = 0.40, P = 0.038), this correlation is absent in elderly subjects (Spearman r = -0.25, P = 0.34). This study provides initial evidence that EV-FNDC5/irisin is reduced in older individuals and loses correlation with BDNF. Our identification of peripheral, exercise-linked factors associated with age may inform biomarker discovery and interventions to promote brain resilience.},
}

@article {pmid41940301,
year = {2026},
author = {Donner, L and Christl, J and Kujovic, M and Supprian, T and Elvers, M},
title = {Platelets from early-stage Alzheimer patients show enhanced amyloid binding, an elevated open canalicular system and sex-specific differences in their activation profile.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1759268},
pmid = {41940301},
issn = {1664-2295},
abstract = {INTRODUCTION: Alzheimer's disease (AD) is associated with neurodegeneration and dementia. Key clinical hallmarksinclude the deposition of amyloid-ß (Aβ) into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA). Currently, anti-Aß antibodies are emerging as possible therapy for AD. Several biomarkers, such as Aß and tau-protein have gained diagnostic relevance for early AD; however, their assessment requires cerebrospinal fluid. Therefore, blood-based biomarkers for AD screening are urgently needed.

METHODS: Patients diagnosed with early AD were analyzed for extracellular Aß binding to platelets, platelet morphology and platelet activation, and were compared with age-matched controls.

RESULTS: Platelet number and size were unaltered between groups. However, platelets isolated from AD patients exhibited increased surface APP/Aβ immunoreactivity compared with age-matched controls. Transmission electron microscopy revealed altered platelet morphology in AD patients, including changes in the number of dense granules and an increased area of the open canalicular system (OCS). While only minor differences in platelet activation were detected between patients and controls, a significant reduction in integrin αIIbβ3 (fibrinogen receptor) activation was observed in platelets from female compared to male AD patients, as determined by flow cytometry.

CONCLUSION: The results presented here emphasize the importance of understanding whether platelets contribute to AD pathology in a sex-specific manner. Furthermore, platelet parameters may serve as promising biomarker for early AD prognosis, as platelets are easily accessible via blood sampling. These parameters may include sex-specific platelet activation profiles, the ability of platelets to bind APP/Aß at their surface, and OCS dimensions assessed by electron microscopy.},
}

@article {pmid41940407,
year = {2026},
author = {Vazquez-Palomo, A and Betegón, C and Weickenmeier, J and Martínez-Pañeda, E},
title = {A computational framework to predict the spreading of Alzheimer's disease.},
journal = {Engineering with computers},
volume = {42},
number = {2},
pages = {78},
pmid = {41940407},
issn = {0177-0667},
abstract = {UNLABELLED: Alzheimer's disease is characterised by the spreading of misfolded proteins and progressive structural changes in the brain. Despite significant clinical research, understanding how microscopic protein dynamics translate into macroscopic tissue degeneration remains a major challenge. In this work, we present a three-dimensional, finite element-based computational framework to model disease progression by combining multi-protein transport and brain tissue deformation within anatomically realistic geometries. The propagation of toxic tau and amyloid-[Formula: see text] proteins is described using reaction-diffusion equations of the Fisher-Kolmogorov type, incorporating prion-like growth mechanisms and anisotropic transport along white matter fibre tracts. Brain atrophy is represented through a hyperelastic constitutive model driven by protein-dependent volume loss. Subject-specific simulations are achieved through an automated preprocessing pipeline that generates finite element meshes and reconstructs axonal orientation fields from medical imaging data. The model reproduces key morphological patterns observed in Alzheimer's disease and shows good quantitative agreement with longitudinal imaging measurements. Overall, the proposed framework offers an extensible computational platform for studying Alzheimer's disease progression across subject-specific brain geometries. The models developed, including the image processing framework (BrainImage2Mesh) and the coupled bio-chemo-mechanical COMSOL finite element implementation, are made freely available to download at https://mechmat.web.ox.ac.uk/codes.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00366-026-02313-5.},
}

@article {pmid41940752,
year = {2026},
author = {Paidi, RK and Gorai, S and Mondal, S and Pahan, K},
title = {L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.},
journal = {Journal of neurochemistry},
volume = {170},
number = {4},
pages = {e70432},
doi = {10.1111/jnc.70432},
pmid = {41940752},
issn = {1471-4159},
support = {1IK6 BX004982//U.S. Department of Veterans Affairs/ ; I01BX005613//U.S. Department of Veterans Affairs/ ; AT10980/NH/NIH HHS/United States ; },
mesh = {Animals ; *Alzheimer Disease/pathology/metabolism/drug therapy/genetics ; Mice ; *Leucine/pharmacology/therapeutic use ; *Autophagy/drug effects/physiology ; *Lysosomes/drug effects/metabolism ; Mice, Transgenic ; *Plaque, Amyloid/pathology/metabolism/drug therapy ; Disease Models, Animal ; Humans ; Up-Regulation/drug effects ; PPAR alpha/metabolism/genetics ; Brain/drug effects/metabolism ; Male ; Astrocytes/drug effects/metabolism ; Mice, Inbred C57BL ; },
abstract = {Twenty different amino acids are required for the human body for proper functioning as amino acids serve as building blocks for proteins. We screened different essential and non-essential amino acids for the ability to stimulate lysosomal biogenesis and, interestingly, found an essential amino acid L-leucine as the most potent one in stimulating lysosomal biogenesis in astrocytes. However, D-leucine remained weaker than L-leucine in terms of stimulation of lysosomal biogenesis. Accordingly, L-leucine increased autophagy in cultured brain cells and in vivo in the brain of 5XFAD mice, one of the animal models of Alzheimer's disease (AD). L-Leucine also stimulated the uptake and degradation of amyloid-β in astrocytes and reduced the plaque load and improved cognitive functions in 5XFAD mice. Although L-leucine was discovered about 200 years back, until now, no receptor has been identified for L-leucine. Here, we noticed that L-leucine binds to the ligand-binding domain of peroxisome proliferator-activated receptor α (PPARα) to activate this nuclear hormone receptor. Accordingly, L-leucine remained ineffective in increasing lysosomal biogenesis and autophagy in PPARα[-/-] brain cells. Lentiviral establishment of full-length PPARα, but not Y314D-PPARα, reinstated the autophagy-stimulating effect of L-leucine in PPARα[-/-] astrocytes, emphasizing the importance of leucine's interaction with the Y314 residue. Moreover, oral L-leucine decreased the plaque load and improved spatial learning and memory in 5XFAD mice, but not in 5XFAD[ΔPPARα] mice (5XFAD lacking PPARα), highlighting the involvement of PPARα in the neuroprotective effects of L-leucine. These results may be beneficial for AD patients.},
}

Animals
*Alzheimer Disease/pathology/metabolism/drug therapy/genetics
Mice
*Leucine/pharmacology/therapeutic use
*Autophagy/drug effects/physiology
*Lysosomes/drug effects/metabolism
Mice, Transgenic
*Plaque, Amyloid/pathology/metabolism/drug therapy
Disease Models, Animal
Humans
Up-Regulation/drug effects
PPAR alpha/metabolism/genetics
Brain/drug effects/metabolism
Male
Astrocytes/drug effects/metabolism
Mice, Inbred C57BL

@article {pmid41940797,
year = {2026},
author = {Rus Prelog, P and Kores Plesničar, B and Zupan, M and Frol, S and Kramberger, MG},
title = {The value and risks of antidepressant therapy in Alzheimer's disease: a field update and its clinical implications.},
journal = {Expert review of neurotherapeutics},
volume = {},
number = {},
pages = {1-15},
doi = {10.1080/14737175.2026.2653170},
pmid = {41940797},
issn = {1744-8360},
abstract = {INTRODUCTION: Depression is one of the most frequent and disabling neuropsychiatric syndromes in Alzheimer's disease (AD), yet antidepressant use is still largely extrapolated from late‑life depression and is poorly aligned with emerging evidence on 'neurodegenerative depression' and disease‑modifying therapies. This article critically re‑examines the clinical value and risks of antidepressants in AD.

AREAS COVERED: Drawing on a narrative search of PubMed/MEDLINE and Embase (January 2000-December 2025) and targeted review of recent guidelines and anti‑amyloid trials, the article synthesizes randomized and observational data on efficacy and safety across antidepressant classes, highlighting modest and inconsistent benefits alongside adverse outcomes such as falls, hyponatremia, bleeding, mortality and possible acceleration of cognitive decline. It integrates mechanistic work on synaptic loss, neuroinflammation and network disruption, discusses the exclusion of depressed patients from anti‑amyloid trials, and reviews rapid‑acting, neuromodulatory and psychosocial strategies within a proposed precision‑prescribing framework based on biomarkers, vascular burden and symptom dimensions.

EXPERT OPINION: Monoaminergic antidepressants in AD should not be abandoned but repositioned as time‑limited, closely monitored options for clearly defined, functionally impairing depressive syndromes, embedded in multimodal care rather than used as default, long‑term treatment for non‑specific distress. Future priorities include biomarker‑stratified AD depression trials, evaluation of interactions with anti‑amyloid therapies and rigorous testing of non‑monoaminergic interventions.},
}

@article {pmid41940807,
year = {2026},
author = {Sayar, G and Parlar, S and Tarikogullari, AH and Erdoğan, MA and Armagan, G and Alptuzun, V},
title = {Synthesis, Bioactivity and Molecular Modeling Studies on Benzimidazole Derivatives and Its Isosteres as Potent AChE/BChE and GSK3β Inhibitors for Alzheimer's Disease.},
journal = {Chemical biology & drug design},
volume = {107},
number = {4},
pages = {e70285},
doi = {10.1111/cbdd.70285},
pmid = {41940807},
issn = {1747-0285},
support = {14-ECZ-044//Ege University Research Foundation/ ; },
mesh = {*Benzimidazoles/chemistry/chemical synthesis/pharmacology/metabolism ; Humans ; *Glycogen Synthase Kinase 3 beta/antagonists & inhibitors/metabolism ; *Cholinesterase Inhibitors/chemistry/chemical synthesis/pharmacology/therapeutic use/metabolism ; *Alzheimer Disease/drug therapy/metabolism ; Cell Line, Tumor ; *Acetylcholinesterase/metabolism/chemistry ; Neuroprotective Agents/pharmacology/chemical synthesis/chemistry ; *Butyrylcholinesterase/metabolism/chemistry ; Hydrogen Peroxide ; Molecular Docking Simulation ; Oxidative Stress/drug effects ; Kinetics ; Structure-Activity Relationship ; },
abstract = {A series of benzimidazoles and its analogs (benzoxazoles and benzothiazoles) bearing a benzohydrazide-hydrazones moiety at the 2-position were designed and synthesized as potential acetylcholinesterase (AChE) inhibitors. Cholinesterase (ChE) inhibitory activity results showed that all compounds displayed good inhibition of AChE, whereas only some of the compounds were active against BChE. Among the title compounds, it was found that all benzimidazole series were selective towards AChE. Kinetic analysis and molecular modeling studies were conducted on the most active compounds, namely 1j for AChE and 3g for BChE inhibition. The kinetic results showed that the tested compounds exhibited a mixed-type inhibition mechanism on both enzymes. In cell culture studies, all compounds were evaluated for their neuroprotective effects against hydrogen peroxide (H2O2)-induced oxidative stress in the SH-SY5Y human neuroblastoma cell line. Several compounds demonstrated more than 30% neuroprotection at a low concentration (1 μM) in the presence of H2O2. Selected compounds, chosen based on their EC50 values, were further examined for their effects on glycogen synthase kinase-3 beta (GSK3β), an enzyme whose activity has been reported to be increased in the brains of patients with Alzheimer's disease (AD). The inhibition of GSK3β was assessed by measuring phosphorylated GSK3β (pGSK3β, Ser9) protein expression via Western Blot analysis under oxidative stress conditions. Among the tested compounds, 1l, 2b, 2j, and 3l significantly increased pGSK3β (Ser9) protein levels compared to cells treated with tideglusib, a known GSK3β inhibitor.},
}

*Benzimidazoles/chemistry/chemical synthesis/pharmacology/metabolism
Humans
*Glycogen Synthase Kinase 3 beta/antagonists & inhibitors/metabolism
*Cholinesterase Inhibitors/chemistry/chemical synthesis/pharmacology/therapeutic use/metabolism
*Alzheimer Disease/drug therapy/metabolism
Cell Line, Tumor
*Acetylcholinesterase/metabolism/chemistry
Neuroprotective Agents/pharmacology/chemical synthesis/chemistry
*Butyrylcholinesterase/metabolism/chemistry
Hydrogen Peroxide
Molecular Docking Simulation
Oxidative Stress/drug effects
Kinetics
Structure-Activity Relationship

@article {pmid41940817,
year = {2026},
author = {Sigg-Alonso, J and Mondragón, JD and González-López, M and Pasaye Alcaraz, EH and Fernández, T},
title = {Functional connectivity alterations in objectively defined subtle cognitive decline: A cross-sectional functional MRI study in cognitively healthy older adults.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435619},
doi = {10.1177/13872877261435619},
pmid = {41940817},
issn = {1875-8908},
abstract = {BackgroundThe aging of the population is leading to an increase in the incidence of neurocognitive disorders, particularly Alzheimer's disease, which has become a significant public health priority. Given the importance of early intervention in neurocognitive disorders, the identification of objectively defined subtle cognitive decline (Obj-SCD) may lead to early identification and better odds of slowing disease progression.ObjectiveTo characterize the connectivity patterns of subjects with Obj-SCD.MethodsFifty-one healthy adults (21 with Obj-SCD and 30 controls) over 55 years old underwent functional MRI and neuropsychological evaluations. MRI scans were conducted using a 3.0 Tesla scanner, and the data were preprocessed and denoised with CONN and SPM software, followed by independent component analysis (ICA) for identifying 20 brain networks and region-of-interest (ROI) analyses for assessing functional connectivity. The thresholds for the results were p < 0.05 for connections and FDR-corrected p < 0.05 for clusters.ResultsCompared with controls, individuals with Obj-SCD exhibited both hyperconnectivity and hypoconnectivity across key brain networks; increased activity was observed in the left angular and right lingual gyri, which showed greater connectivity with the language and visual networks but reduced connectivity with the somatosensory and dorsal attention networks. The default mode and central executive networks also showed functional connectivity alterations, whereas the salience network exhibited hypoconnectivity.ConclusionsThe connectivity alterations of individuals with Obj-SCD may reflect compensatory mechanisms, early network disruptions, or both. fMRI-based analyses could aid in detecting these early changes, providing opportunities for interventions that may slow or prevent further cognitive decline.},
}

@article {pmid41940821,
year = {2026},
author = {Munro, CE and Beltran, J and Palmer, P and Farrell, M and Hanseeuw, B and Rentz, DM and Buckley, R and Properzi, M and Vannini, P and Amariglio, RE and Quiroz, YT and Yang, HS and Blacker, D and Sperling, RA and Johnson, KA and Marshall, GA and Gatchel, JR},
title = {Baseline cortical amyloid-β levels are associated with subsequent study-partner-rated apathy in community-dwelling older adults.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261436755},
doi = {10.1177/13872877261436755},
pmid = {41940821},
issn = {1875-8908},
abstract = {BackgroundApathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) and has been linked to greater levels of AD biomarkers (amyloid-β, tau). However, it is unclear whether early patterns of amyloid deposition may impact development of apathy symptoms in the future.ObjectiveWe sought to examine whether amyloid-β levels, both globally and in brain regions associated with motivation, could predict future apathy symptoms.MethodsParticipants (n = 199, mean age = 79.9) were part of the Harvard Aging Brain Study, a longitudinal observational cohort of individuals without cognitive or psychiatric impairment at baseline. All underwent MRI and Pittsburgh Compound B (PiB)-PET for amyloid-β at baseline and completed questionnaires of self- and study-partner-rated apathy 7.8 ± 1 years later using the Apathy Evaluation Scale. Linear regression models assessed whether regional PiB levels predicted future apathy scores.ResultsHigher baseline cortical PiB levels in a frontal, lateral parieto-temporal, and retrosplenial aggregate were associated with greater study-partner-rated apathy, but not self-rated apathy, and no specific regional associations were observed outside of the aggregate.ConclusionsThese results provide insight into early neurobiological underpinnings of AD-related apathy. Additionally, these data may have clinical implications regarding the risk of developing apathy symptoms in amyloid-β-positive individuals as cognition declines.},
}

@article {pmid41940826,
year = {2026},
author = {Hayakawa, N and Takeda, S and Takahashi, H and Arisawa, A and Matsuo, C and Tomiyama, N and Nakajima, T and Miki, S and Kishino, Y and Teshirogi, S and Yamamoto, S and Okawara, M and Ito, Y and Takami, Y and Takeya, Y and Yamamoto, K and Morishita, R},
title = {Distinct patterns of microstructural brain changes in Alzheimer's disease subtypes: Diffusion MRI metrics in braak stage-related regions.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261436754},
doi = {10.1177/13872877261436754},
pmid = {41940826},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) is pathologically defined by the accumulation of amyloid-β and phosphorylated tau and subsequent neuronal death. These neuropathological changes typically accumulate in the medial temporal lobe before spreading to other cortical regions (Braak staging pattern). Recent studies using postmortem brain tissue and neuroimaging data have revealed AD subtypes with distinct neuropathological patterns. Hippocampal-sparing (HpSp) subtype of AD shows the preservation of medial temporal lobe volume, compared to typical AD; however, underlying changes in the brain microstructure remain largely unclear.ObjectiveWe used Neurite Orientation Dispersion and Density Imaging (NODDI) to investigate the microstructural signatures in each AD subtype.MethodsWe defined typical and HpSp AD based on visual assessment scales of brain MRI, among individuals with mild cognitive impairment who were positive for core AD cerebrospinal fluid markers. We set regions of interest in Braak stage (BS)-related areas (hippocampus (BS II), precuneus (BS V), and postcentral gyrus (BS VI)) and compared NODDI metrics, including intracellular volume fraction, orientation dispersion index, and isotropic volume fraction (Viso), among typical AD, HpSp AD, and non-AD control groups.ResultsNODDI metrics in the hippocampus were significantly different between the typical and HpSp AD groups. Notably, the hippocampal NODDI values in the HpSp AD group were comparable to those of the control group. Viso values in the precuneus were significantly higher in HpSp AD, compared to typical AD.ConclusionsThis suggests that AD subtypes have distinct patterns of microstructural changes in BS-related brain regions.},
}

@article {pmid41940827,
year = {2026},
author = {Ding, K and Jiang, W and Lei, M and Gao, Y},
title = {Uncovering polygenic and local genetic overlap between sarcopenia and Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261436016},
doi = {10.1177/13872877261436016},
pmid = {41940827},
issn = {1875-8908},
abstract = {BackgroundSarcopenia and Alzheimer's disease (AD) are prevalent comorbidities in older adults. Their common genetic basis remains unclear.ObjectiveUtilizing Genomic Structural Equation Modeling, we used European-ancestry genome-wide association study (GWAS) summary statistics to model sarcopenia-related traits. Multiple AD GWAS datasets and the sarcopenia GWAS dataset were used to conduct cross-trait analyses.MethodsGenome-wide and local genetic correlations were assessed using LDSC and LAVA. MiXeR was applied to evaluate shared versus trait-specific variants. Shared loci were identified using conjFDR. Candidate genes were further explored via tissue-specific expression (MetaXcan) and Mendelian randomization (MR).ResultsLDSC analysis revealed no significant genome-wide genetic correlation between AD and sarcopenia (rg = 0.020, p = 0.178). Bivariate LAVA analysis identified significant local genetic correlations at three specific genomic regions (chr3:183.2-184.5 Mb, chr8:144.9-146.3 Mb, and chr8:27.4-28.3 Mb; p < 0.05/90). MiXeR indicated moderate polygenic overlap (228 shared variants). ConjFDR identified 20 shared loci, and MetaXcan highlighted ETHE1, FEZ2, PHLDB3, and PINLYP. MR analysis indicated a positive causal effect of FEZ2 in excitatory neurons on AD and sarcopenia risk (FDR < 0.05).ConclusionsThis study indicates no significant genome-wide genetic correlation between sarcopenia and AD, while suggesting the presence of localized shared genetic signals at specific genomic regions. Dysregulation of the cytoskeleton and autophagy pathways may contribute to both sarcopenia and AD. FEZ2, ETHE1, PHLDB3, and PINLYP expression in muscle and brain may contribute to the comorbidity between sarcopenia and AD. Overall, these findings provide exploratory evidence for local shared genetic architecture between sarcopenia and AD.},
}

@article {pmid41940830,
year = {2026},
author = {Zou, H and Wang, T and Huynh, K and Meikle, PJ and Kaddurah-Daouk, R and Luo, S and , and , },
title = {Plasma lipid trajectories improve prediction of future Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435212},
doi = {10.1177/13872877261435212},
pmid = {41940830},
issn = {1875-8908},
abstract = {BackgroundEarly identification of individuals at elevated risk for Alzheimer's disease (AD) is critical for prevention. Blood-based biomarkers offer scalable alternatives to cerebrospinal fluid and imaging, but the prognostic value of longitudinal plasma lipid trajectories remains unclear.ObjectiveTo evaluate whether multi-year plasma lipid trajectories improve prediction of AD conversion beyond demographic, clinical, genetic, and neuropsychological measures.MethodsWe studied 1150 cognitively normal or mildly impaired Alzheimer's Disease Neuroimaging Initiative participants; 329 progressed to AD dementia over a mean follow-up of 2.3 years. Plasma lipidomics quantified 749 lipid species by high-resolution LC-MS. Trajectories were summarized using functional principal component analysis and related to time to conversion using covariate-adjusted Cox proportional hazards models. Predictive performance was assessed by concordance index and likelihood-ratio tests.ResultsCross-sectional lipid profiles modestly improved prediction beyond demographic and clinical covariates, and longitudinal lipid trajectories yielded small additional gains. Ether-linked triglycerides showed the strongest longitudinal associations with conversion, with TG(O-50:1) [NL-18:1] exhibiting the most robust signal. Neuropsychological measures provided substantially stronger discrimination, and lipid trajectories added limited value once cognitive information was included. Nevertheless, longitudinal lipid changes contributed consistent improvements in models without neuropsychological predictors, supporting their role as complementary blood-based markers in settings where standardized cognitive assessments are unavailable or impractical.ConclusionsPlasma lipid trajectories capture biologically relevant metabolic change associated with AD progression and provide complementary predictive information. Longitudinal lipidomic profiling may support early risk stratification and cohort enrichment when cognitive assessments are unavailable.},
}

@article {pmid41940832,
year = {2026},
author = {Gu, Q and Xie, Y and Zhao, Z and Zhuang, Z and Yang, L and Huang, H and Li, H and Pi, S and Chen, F and Gong, C and He, Y},
title = {CeRNA regulatory network of cerebral microvascular dysfunction in early development of APP/PS1 mice model of Alzheimer's disease.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435563},
doi = {10.1177/13872877261435563},
pmid = {41940832},
issn = {1875-8908},
abstract = {BackgroundGiven the global aging trend and the rising challenge of Alzheimer's disease (AD), accumulating evidence identifies cerebral microvascular dysfunction as an early pathological event. Hence, elucidating the key molecular regulators of cerebral microvascular function is critical for developing early intervention strategies.ObjectiveTo identify key genes associated with cerebral microvascular dysfunction in early-stage AD based on transcriptomics and to investigate the competing endogenous RNA (ceRNA) network involving long non-coding RNA (lncRNA).MethodsImmunofluorescence staining for CD31 was conducted on cerebral cortical sections from 1-month-old APP/PS1 and wild-type (WT) mice. Cerebral cortex and microvascular fractions were isolated for qPCR and western blot analysis of microvascular functional molecules. Following differential expression analysis, we performed functional and pathway enrichment, PPI network construction, ClueGo module analysis, and CFG prioritization to screen for core genes regulating cerebral microvascular function. A comprehensive ceRNA network was then established by integrating multi-database miRNA target predictions with RNA expression correlation data.ResultsOne-month-old AD mice exhibited both reduced cerebral microvascular density and average vessel length, along with significant disruption in the expression of blood-brain-barrier proteins. Transcriptomic profiling identified 956 differentially expressed transcripts, including 539 lncRNAs, 412 mRNAs, and 5 miRNAs. By integrative bioinformatics analysis, we identified 11 hub genes primarily involved in vascular contraction and circadian regulation, and constructed a comprehensive ceRNA network comprising 7 mRNAs, 41 miRNAs, and 46 lncRNAs.ConclusionsOur results reveal that early-stage AD is characterized by cerebral microvascular dysfunction, primarily mediated through impaired vascular contraction and disrupted circadian rhythm regulation.},
}

@article {pmid41940846,
year = {2026},
author = {Costa, T and Liloia, D and Premi, E and Ashton, N and Zettemberg, H and Blennow, K and Padovani, A and Borroni, B},
title = {A Bayesian classification model for differential diagnosis of Alzheimer's disease and frontotemporal dementia using plasma biomarkers.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261439950},
doi = {10.1177/13872877261439950},
pmid = {41940846},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) and frontotemporal dementia (FTD) have distinct pathologies but frequently overlapping clinical presentations, making early and atypical differential diagnosis challenging. Blood-based biomarkers offer a minimally invasive alternative to cerebrospinal fluid and neuroimaging measures, yet their diagnostic performance-alone and in combination-remains to be fully established.ObjectiveTo quantify the discriminative ability of plasma biomarkers for differentiating AD, FTD, and healthy controls (HC).MethodsWe used a fully Bayesian classification framework, estimating Bayesian logistic regression models for all single, pairwise, and triplet combinations of six plasma biomarkers-phosphorylated tau at threonine 217 (pTau217), brain-derived tau (BD-Tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), amyloid-β40 (Aβ40), and amyloid-β42 (Aβ42)-in AD (n = 97), FTD (n = 255), and HC (n = 70). Models were fitted across three contrasts (AD versus HC, FTD versus HC, AD versus FTD) and evaluated via posterior distributions of cross-validated AUC, precision, recall, F1 score, and Brier score.ResultsAcross 41 candidate models, NfL was the top single biomarker (mean AUC = 0.85), achieving strong discrimination for FTD versus HC (AUC = 0.94). The best two-marker panel (pTau217 + NfL) improved AD versus HC (AUC = 0.96) and AD versus FTD (AUC = 0.90). Adding Aβ42 produced the highest-ranked triplet (AUC = 0.95) with modest, consistent gains. Posterior coefficients were biologically coherent (AD-specific pTau217 effects; severity-linked NfL), and calibration was satisfactory, with minor overconfidence only at extreme probabilities.ConclusionsA parsimonious pTau217 + NfL panel captures most diagnostic information in the full plasma profile, providing an accurate probabilistic classifier with interpretable uncertainty to support differential diagnosis and clinical triage in precision neurology.},
}

@article {pmid41940848,
year = {2026},
author = {Kuchipudi, JD and Menon, J and Kantipudi, SJ and Vinoth, S and Vanisree, AJ and Hemamalini, AJ},
title = {Gender differences in methylcobalamin, folate, homocysteine, and hemoglobin levels among urban, community dwelling, elderly with mild cognitive impairment in a South Indian city: A cross-sectional study.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261436756},
doi = {10.1177/13872877261436756},
pmid = {41940848},
issn = {1875-8908},
abstract = {BackgroundVitamin B12 and folate deficiencies are associated with cognitive decline, yet evidence for their role in mild cognitive impairment (MCI) remains inconclusive, particularly how it differs across genders.ObjectiveTo evaluate the prevalence of vitamin B12, vitamin B9, Homocysteine, and hemoglobin levels among male and female urban, community-dwelling elderly individuals with MCI and to assess gender-specific differences in these biochemical parameters.MethodsA cross-sectional study was conducted among 128 urban, community-dwelling elderly individuals (60 + years) with MCI in South India. Serum levels of vitamin B12, folate, homocysteine, and hemoglobin were evaluated alongside cognitive assessment. Multiple regression analysis was performed to evaluate the association between biomarkers and cognitive function adjusting for sociodemographic variables.ResultsThis study revealed a high prevalence of vitamin B12 (78.1%), folate (99.2%) deficiencies and anemia (64.1%), alongside elevated homocysteine levels in 87.5% of participants. No significant association was found between mean scores of cognition in MCI and vitamin B12, folate, or homocysteine levels. Females had significantly lower mean hemoglobin levels than males (p = 0.03). Cognitive scores were relatively higher in females despite their lower socioeconomic status and hemoglobin levels.ConclusionsGender disparities in hemoglobin levels highlight the importance of addressing nutritional inequities. However, vitamin B12 and folate levels may not strongly influence MCI. Routine assays for these vitamins in elderly individuals with cognitive impairment should be reconsidered in resource-constrained settings.},
}

@article {pmid41940849,
year = {2026},
author = {de Levante Raphael, D},
title = {Persistent functional impairment as a preclinical signal of Alzheimer's disease: Advancing dementia prognostication through the natural history of function.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261438521},
doi = {10.1177/13872877261438521},
pmid = {41940849},
issn = {1875-8908},
abstract = {Early identification of Alzheimer's disease remains restricted due to overreliance on cognitive testing and biomarker accessibility. The study by Ghahremani et al. demonstrates that persistent, however not transient, functional impairment in cognitively normal older adults robustly predicts incident cognitive decline and dementia. This commentary positions their findings within social, behavioral, and public-health frameworks, emphasizing functional trajectories as ecologically valid, scalable markers of preclinical disease. By operationalizing function through persistence over time, this work advances dementia projections beyond cross-sectional assessment and supports integration of functional monitoring into population-level prevention, clinical trials, and equity-focused early detection strategies.},
}

@article {pmid41940854,
year = {2026},
author = {Alcalá Ramírez Del Puerto, JM and Ortega-Madueño, I and Gil-Moreno, MJ and Abizanda-Saro, P and Palacios-Sarmiento, M and Millán-Guirado, R and Cruz-Cárdenas, M and Matías-Guiu, JA},
title = {Apolipoprotein E proteotyping as a valid alternative to genotyping in clinical practice.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261438522},
doi = {10.1177/13872877261438522},
pmid = {41940854},
issn = {1875-8908},
abstract = {The apolipoprotein E ε4 allele (APOE ε4) is associated with higher incidence of amyloid-related imaging abnormalities in patients with Alzheimer's disease undergoing anti-amyloid therapy, underscoring the importance of allele status testing. In this study, plasma ApoE4 levels were measured in 70 participants using Lumipulse[®]G Pan-ApoE and ApoE4 assays and compared with traditional genotyping. ApoE4 concentrations and ratio ApoE4/Pan-ApoE differed significantly across non-ε4, ε3/ε4, and ε4/ε4 groups. No correlation was observed with age, sex, creatinine levels, or AD cerebrospinal fluid biomarkers. Diagnostic performance was excellent, indicating that proteotyping of ApoE can accurately classify the main APOE haplotypes.},
}

@article {pmid41940855,
year = {2026},
author = {Liu, M and Bhatt, K and Giaever, MF and Ardekani, BA and Reichert Plaska, C and , and Ghanbarian, E},
title = {Sex differences in cognitive performance in Alzheimer's disease: Insights from the ADAS-Cog-13.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261440125},
doi = {10.1177/13872877261440125},
pmid = {41940855},
issn = {1875-8908},
abstract = {BackgroundSex differences in Alzheimer's disease (AD) are well recognized, yet their implications for cognitive assessment remain unclear. Females often demonstrate better cognitive performance than males despite comparable levels of neurodegeneration, which may delay diagnosis.ObjectiveTo evaluate sex differences in cognitive performance across AD continuum.MethodsUsing data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we examined sex differences in total and item-level performance on the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-13) among cognitively normal (CN) individuals and patients with AD. Regression models were performed, adjusting for hippocampal parenchymal fraction, age, and education.ResultsThe study included 656 CN participants (59% female) and 193 AD patients (45% female). Among CN individuals, female sex was associated with lower total ADAS-Cog-13 scores (β = -2.09, p < 0.0001). CN females demonstrated superior performance on multiple verbal subdomains, including word recall, delayed word recall, naming, and word recognition. In contrast, no significant sex difference was observed in total ADAS-Cog-13 scores among AD patients, although males performed better than females on delayed word recall. Across both groups, greater hippocampal integrity was strongly associated with better global and domain-specific cognitive performance.ConclusionsSex differences in ADAS-Cog-13 performance are evident in cognitively normal individuals but largely attenuated in AD patients. Superior verbal performance in CN females, independent of hippocampal integrity, may mask early cognitive decline and contribute to delayed diagnosis. These findings highlight the importance of accounting for sex when interpreting cognitive test results, particularly in preclinical stages of AD.},
}

@article {pmid41940859,
year = {2026},
author = {Geda, YE and Krell-Roesch, J and Bekele, K and Gunning, JA and Zaniletti, I and Eagan, D and Demeke, M and Khan, N and Chahal, G and Smith, T and DeCuna, C and Aliskevich, EL and Hettiwatte, Y and Ransdell, M and Racette, SB},
title = {Time-restricted eating in Alzheimer's disease (TREAD): A call for research.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261438520},
doi = {10.1177/13872877261438520},
pmid = {41940859},
issn = {1875-8908},
abstract = {Fasting is part and parcel of the practice of various religious groups. In the scientific literature, the term intermittent fasting (IF) was first reported in a 1946 paper demonstrating its association with increased longevity in rodents. Research has extended IF, particularly time-restricted eating (TRE), to Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by neuritic plaques, neurofibrillary tangles, and neuronal loss. AD manifests in asymptomatic, mild cognitive impairment (MCI), and dementia phases. Delaying progression from MCI to dementia by one year could reduce dementia prevalence by millions. Currently, no pharmacological treatments can reverse or arrest MCI progression to dementia, making exploration of non-pharmacological interventions critical. TRE is a promising approach. AD brains exhibit decreased glucose uptake, while ketone utilization remains intact. Fasting for at least 8-12 h induces a cascade of molecuar events that lead to a metabolic switch from glucose to ketone utilization, providing an alternative energy source for AD brains. Preclinical studies demonstrate that TRE enhances cognitive function via hippocampal neurogenesis, autophagy, and reduced neuroinflammation. Human studies on TRE in MCI are limited but promising, often focusing on cardiometabolic outcomes, with little known about TRE targeting MCI. This review synthesizes current evidence on TRE and cognitive outcomes in humans, non-human primates, and rodents, and describes ongoing trials in MCI patients. We propose a theoretical model of direct and indirect pathways linking TRE with resistance to AD in the brain parenchyma, and identify gaps in knowledge regarding long-term cognitive effects and mechanistic pathways of TRE in MCI, urging rigorous clinical trials to establish TRE as a safe and possibly effective strategy to delay MCI progression to dementia.},
}

@article {pmid41940869,
year = {2026},
author = {Sharif-Askari, Z and Atoui, K and El Zein, W and Rizk, M and Sharif Askari, E},
title = {From periodontitis to neurodegeneration: Can probiotics modulate the P. gingivalis-amyloid pathway in Alzheimer's disease?.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261432686},
doi = {10.1177/13872877261432686},
pmid = {41940869},
issn = {1875-8908},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the gradual destruction of cognitive and behavioral functions. Despite the continuous research efforts, there is still no cure for this disease. In recent years, researchers have investigated Porphyromonas gingivalis (P. gingivalis) as a potential cause of AD. P. gingivalis-lipopolysaccharides (LPS) and gingipains have been implicated in neuroinflammatory cascades relevant to AD. The gut-brain axis provides a pathway for microbial migration, immune activation, and regulation of the central nervous system function. Emerging evidence suggests that selected probiotics may modulate these pathways by restoring microbial balance, reinforcing epithelial barrier function, and regulating innate and adaptive immunity. Importantly, much of the evidence and mechanistic support for these effects derives from preclinical and animal studies, whereas human data remain limited to associative findings and early-stage clinical trials. Early clinical trials report modest improvements in cognitive scores and systemic inflammatory markers. Strain selection, dose, and treatment duration make direct comparisons challenging. This review integrates the literature on the links between P. gingivalis and AD, suggesting that probiotics may be used as neuroprotective agents. Taken together, current preclinical signals are consistent with the potential of probiotics as feasible adjuncts, pending confirmatory trials with standardized formulations.},
}

@article {pmid41941099,
year = {2026},
author = {Hayibor, LA and Anokhin, A and Fisher, SL and Goate, A and Foroud, TM and Schindler, SE and Bierut, LJ and Hartz, SM},
title = {The relationship between alcohol use disorder, measures of cognitive decline, and Alzheimer disease biomarkers in middle aged and older adults.},
journal = {Alcohol, clinical & experimental research},
volume = {50},
number = {4},
pages = {e70278},
doi = {10.1111/acer.70278},
pmid = {41941099},
issn = {2993-7175},
support = {R01 AG065234/AG/NIA NIH HHS/United States ; R01 AG084723/AG/NIA NIH HHS/United States ; P01 AG026276/AG/NIA NIH HHS/United States ; R01 AA029308/AA/NIAAA NIH HHS/United States ; U10 AA008401/AA/NIAAA NIH HHS/United States ; UL1TR002345/TR/NCATS NIH HHS/United States ; },
mesh = {Humans ; Aged ; Male ; Female ; *Alzheimer Disease/blood/epidemiology/diagnosis/psychology ; Biomarkers/blood ; Middle Aged ; Aged, 80 and over ; Amyloid beta-Peptides/blood ; *Alcoholism/blood/epidemiology/psychology/complications ; *Cognitive Dysfunction/blood/epidemiology ; tau Proteins/blood ; Peptide Fragments/blood ; },
abstract = {BACKGROUND: Alcohol use disorder (AUD) is associated with increased risks of some neuropsychiatric conditions and early-onset dementia. However, the association between Alzheimer disease (AD) and AUD is poorly characterized. To address this, we studied associations between AUD, cognition, and measures of AD neuropathology.

METHODS: We measured a lifetime history of AUD, cognitive decline, and blood biomarkers for AD in middle-aged and older participants (47-87 years) from the St. Louis site of the Collaborative Study on the Genetics of Alcoholism (COGA) (N = 392). Cognitive decline was measured using the Eight-item Informant Interview to Differentiate Aging and Dementia (AD8) (N = 366); 154 individuals had AD biomarkers derived from plasma measurements (Amyloid Probability Score 2, Aβ42/Aβ40, and %p-tau217). We used Poisson regression models to evaluate the relationship between AUD, age, and cognitive decline. AUD was categorized as no AUD, mild AUD, or moderate-to-severe AUD, and age was modeled as a piecewise linear variable segmented by decade. Linear regressions were used to assess the association between AD blood biomarkers and AUD.

RESULTS: Analyses revealed a significant association between moderate-to-severe AUD and increased cognitive decline in middle-aged and older adults (RR = 1.4, p < 0.001). While a greater proportion of participants with moderate-to-severe AUD met the Aβ42/Aβ40 threshold for predicting elevated brain amyloid compared to those with mild or no AUD, consistent with our hypothesis, this trend did not achieve statistical significance.

CONCLUSIONS: These results underscore the importance of addressing AUD as a potentially modifiable risk factor for cognitive decline in middle aged and older adults. Further study is needed to understand the link between AUD and AD biomarkers.},
}

Humans
Aged
Male
Female
*Alzheimer Disease/blood/epidemiology/diagnosis/psychology
Biomarkers/blood
Middle Aged
Aged, 80 and over
Amyloid beta-Peptides/blood
*Alcoholism/blood/epidemiology/psychology/complications
*Cognitive Dysfunction/blood/epidemiology
tau Proteins/blood
Peptide Fragments/blood

@article {pmid41941130,
year = {2026},
author = {Tosun, S and Karalı, FS and Eskioğlu, Eİ and Çavdar, D and Dicle, M and Çınar, N and Macoir, J},
title = {Normative data and clinical validity of verb and phonemic fluency tasks in Turkish-speaking older adults.},
journal = {Neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/neu0001089},
pmid = {41941130},
issn = {1931-1559},
abstract = {OBJECTIVE: Verbal fluency tasks are commonly used in clinical neuropsychology to assess language and executive functions. Verb fluency and phonemic fluency are sensitive to age-related cognitive decline and neurodegenerative conditions such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, normative data for these tasks remain limited in Turkish-speaking populations, especially when culturally adapted phonemic fluency measures are employed. This study aimed to (a) provide normative data for verb fluency and Turkish-adapted K-A-S phonemic fluency tasks in healthy middle-aged and older adults, and (b) examine the discriminant validity of these tasks in distinguishing healthy controls from individuals with MCI and AD.

METHOD: In the normative phase, 357 healthy adults were assessed and stratified by age and education. Norms were reported as regression-based z scores and percentile tables.

RESULTS: In the clinical phase, 150 participants (50 healthy, 60 MCI, and 40 AD) completed the tasks. Kruskal-Wallis and post hoc analyses revealed significant group differences across all fluency measures. Healthy controls outperformed both clinical groups, and the MCI group scored higher than the AD group, especially on K fluency and total K-A-S scores.

CONCLUSIONS: These findings highlight the diagnostic value of verb and phonemic fluency tasks and the importance of using culturally appropriate norms in Turkish-speaking populations for early detection of cognitive impairment. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41941131,
year = {2026},
author = {Zhao, Y and Zhang, J and Zhao, Y and Yuan, Y and Shen, J and Peng, H and Li, J},
title = {Cognitive health on the fingertips: Fine motor deficiencies for assessing the risk of mild cognitive impairment in the aging adults.},
journal = {Neuropsychology},
volume = {},
number = {},
pages = {},
doi = {10.1037/neu0001074},
pmid = {41941131},
issn = {1931-1559},
support = {//National High Level Hospital/ ; //Chinese Academy of Medical Sciences; Interdisciplinary Research Program on Frontiers of Medical Health/ ; //Artificial Intelligence Beijing Municipal Science & Technology Commission/ ; },
abstract = {OBJECTIVE: Mild cognitive impairment (MCI) represents a critical prodromal stage associated with Alzheimer's disease and other age-related neurocognitive conditions in middle-old aging adults, yet research exploring its association with fine motor skill deficits remains relatively limited. This study explores the specific characteristics of fine motor function in middle-old aging adults with MCI using the latest wearable inertial motion capture technology.

METHOD: A computerized system with wearable inertial motion capture technology captured and assessed fine motions. The least absolute shrinkage and selection operator-based machine learning algorithm was utilized to construct a nomogram. The discriminatory ability of the model was determined by calculating the area under the curve. Decision curve analysis, clinical impact curve analysis, and bootstrap validation were used to evaluate and validate the stability of models.

RESULTS: A total of 289 participants aged ≥50 were recruited, of which 140 participants experienced MCI. Compared with the control group, patients with MCI showed significantly poorer fine motor performance in hand function assessment tasks. Spearman correlation analysis revealed a stronger correlation between fine motor function and visuospatial/executive function. A multivariable nomogram model based on fine motion parameters showed satisfactory discrimination, with an area under the curve of .773. Decision curve analysis, clinical impact curve analysis, and bootstrap validation demonstrated the good clinical utility and stability of the model.

CONCLUSIONS: Poor motor functioning was associated with MCI status. The nomogram model, based on fine motion parameters, demonstrated moderate discriminative performance in assessing the risk of MCI, serving as a valuable clinical supplement. (PsycInfo Database Record (c) 2026 APA, all rights reserved).},
}

@article {pmid41941206,
year = {2026},
author = {Andrews, SJ and Yaffe, K},
title = {Advancing Precision Dementia Care With Genetic-Exposome Risk Assessment.},
journal = {JAMA neurology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaneurol.2026.0573},
pmid = {41941206},
issn = {2168-6157},
}

@article {pmid41941211,
year = {2026},
author = {Kumari, K and Kumar, N and Ramakrishnan, V},
title = {Electric Field Directed Structural Modulation and Nanoassembly of Peptide Hydrogels.},
journal = {Langmuir : the ACS journal of surfaces and colloids},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.langmuir.5c06894},
pmid = {41941211},
issn = {1520-5827},
abstract = {This study presents a novel approach to modulate peptide self-assembly, solubility, and functional properties by utilizing an electric field as an external stimulus. Three short, heterochiral tripeptides, P1, P2, and P3, were designed based on their ability to form hydrogels. We demonstrate that the structural and functional properties of peptide-based hydrogels can be modulated upon exposure to an electric field. Our findings indicate that the external electric field does not alter the secondary structure of the designed peptides, however, the electric field plays a significant role in regulating the supramolecular assembly at the nanoscale. Morphological studies using field emission-scanning electron microscopy (FE-SEM), field emission-transmission electron microscopy (FE-TEM), and atomic force microscopy (AFM) images indicate a pronounced transition from a nanofibrillar architecture in control experiments with no electric field to the formation of nanoflakes, vesicular structures, and globular aggregates upon exposure to varying electric fields. We further examined the effect of the electric field in modulating the electrical conductivity of the peptide hydrogel. Additionally, an inverse relationship was observed between the peptide solubility and the mechanical robustness of the hydrogel. These findings suggest that the electric field can noninvasively perturb and modulate the solubility and aggregation characteristics of peptides. This approach also suggests a promising option for developing therapeutic interventions that enhance the solubility and reduce the fibrillation for several disease conditions, such as Alzheimer's and Parkinson's.},
}

@article {pmid41941234,
year = {2026},
author = {Oo, WJ and Sia, WT and Lee, JY and Chen, CH and Chang, WL and Chye, SM},
title = {The Role of Presynaptic Cytomatrix Protein Bassoon (BSN) in Tau Pathology and Propagation.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273400895251129055504},
pmid = {41941234},
issn = {1996-3181},
abstract = {Neurodegenerative disorders have become a global health threat following a prolonged lifespan, with the majority involving the accumulation and propagation of pathological tau. Tau oligomers can migrate to presynaptic terminals and interact with surrounding proteins, among which Bassoon (BSN) is one that selectively binds to and colocalises with misfolded tau. Studies have reported numerous implications of BSN mutations in tau pathology, including promoting tau seeding activity, hyperphosphorylation, misfolding, and aggregation. These eventually lead to the formation of neurofibrillary tangles in tauopathies. Given the BSN's physiological role in maintaining synapses, its mutation also impairs synaptic integrity. These abnormalities are consistently attenuated by downregulating BSN levels. However, BSN downregulation can lead to tau hyperphosphorylation via an alternative pathway, CDK5 hyperactivity. Current findings hypothesize that BSN reduces tau clearance by inhibiting proteasome activity. It is also suggested that BSN can impair dopaminergic pathways prior to the detection of tau pathological features. Tunnelling nanotubes also emerge as a potential interneuronal route for BSN-mediated tau spread. Despite a lack of clinical evidence, findings from postmortem samples, in vitro, and preclinical models highlight BSN as a potential candidate for tau-targeting therapies, indicating its role in the pathological development of tau. The involvement of BSN in tau seeding might also resolve challenges posed by tau-targeting drugs during clinical trials. Hence, this article aims to provide new insights into recent findings on BSN and tau with reference to previous studies. We will discuss the possible mechanisms involved, along with the future therapeutic value of BSN in the treatment of tauopathies.},
}

@article {pmid41941239,
year = {2026},
author = {Wang, N and Wen, H and Sun, Y and Xu, W and Shen, X and Wang, R},
title = {Effects of Hesperetin Early Intervention on Brain Neurons and Microglia in APPswe/PS1dE9 Mice.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273418623251203072424},
pmid = {41941239},
issn = {1996-3181},
abstract = {INTRODUCTION: Neuroinflammation and microglial dysfunction play central roles in the pathogenesis of Alzheimer's disease (AD). This study investigated whether early intervention with hesperetin, a citrus flavonoid, could attenuate neuroinflammation and modulate microglial polarization in both wild-type (WT) and APPswe/PS1dE9 transgenic (TG) mice.

METHODS: Three-month-old male C57BL/6J WT and APPswe/PS1dE9 TG mice were administered hesperetin (10 or 20 mg/kg/day for WT; 20, 40, or 80 mg/kg/day for TG) or vehicle for six months. Neuronal morphology was assessed using thionine staining. Microglial polarization was evaluated via CD11b/iNOS and CD11b/Arginase-1 immunofluorescence. Protein expression of CD11b, iNOS, Arginase-1, and TREM2 was measured by Western blot, and cytokine levels (TNF-α, IL-10) were quantified by ELISA.

RESULTS: In WT mice, hesperetin improved neuronal integrity, reduced M1 markers (CD11b⁺/ iNOS⁺ cells, iNOS, TNF-α), and enhanced M2 markers (CD11b⁺/Arginase-1⁺ cells, Arginase-1, TREM2). TG mice exhibited exacerbated neuroinflammation and neuronal loss compared to WT controls, which was significantly mitigated by hesperetin treatment. All hesperetin doses in TG groups reduced pro-inflammatory markers and increased anti-inflammatory and repair-associated factors.

DISCUSSION: These results indicate that hesperetin shifts microglial polarization toward the protective M2 phenotype, potentially via TREM2 upregulation, thereby reducing neuroinflammation and neuronal damage. This effect was observed in both age-related and Aβ-driven pathology, suggesting a dual role for hesperetin in immunomodulation and neuroprotection.

CONCLUSION: Early hesperetin intervention exerts neuroprotective effects by rebalancing microglial polarization and enhancing TREM2 expression, highlighting its potential as a preventive strategy against AD-related neuroinflammation.},
}

@article {pmid41941281,
year = {2026},
author = {Subramanian, I and Surajambika, RR and Sekar, D and Natarajan, R and Nagarajan, NC},
title = {A Systematic Review on Isoquinoline Derivatives as Emerging Multi-target Agents in Alzheimer's and Parkinson's Disorder Therapy.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249401454260108062419},
pmid = {41941281},
issn = {1875-6166},
abstract = {INTRODUCTION: Neurodegenerative disorders, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease, are characterized by progressive neuronal loss driven by damage or apoptosis. Although their precise etiologies remain unclear, neuronal degeneration is a common pathological hallmark.

METHODS: This review compiles and critically evaluates studies investigating the potential of isoquinoline derivatives to mitigate neurodegeneration. Particular attention is given to their inhibitory effects on key enzymes implicated in these disorders and structural modifications aimed at improving potency and reducing toxicity.

RESULTS: Experimental findings demonstrate that isoquinoline derivatives exhibit significant inhibitory activity against several neurodegeneration-related enzymes. These compounds show promise in attenuating disease progression in preclinical models, supporting their potential as therapeutic leads.

DISCUSSION: Isoquinoline derivatives display multitarget properties, and structural optimization has enhanced their efficacy and safety profiles. Their multifunctional nature could offer advantages over current single-target therapies by improving efficacy and reducing adverse effects.

CONCLUSION: Isoquinoline derivatives represent promising scaffolds for developing novel therapeutics targeting neurodegenerative disorders. However, most data are limited to in vitro and earlystage preclinical studies. Comprehensive mechanistic investigations, standardized in vivo evaluations, and early-phase clinical trials are required to establish their pharmacokinetics, blood-brain barrier permeability, safety, and therapeutic potential.},
}

@article {pmid41941282,
year = {2026},
author = {Agrawal, MM and Mittal, P},
title = {Emerging Therapies and Research in Alzheimer's Disease: A Critical Review.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249403872251208145159},
pmid = {41941282},
issn = {1875-6166},
abstract = {Alzheimer's disease, an extremely prevalent neurological illness and the leading cause of dementia globally, is an extremely prevalent neurological illness and is the leading cause of dementia globally. There are a few treatment options for AD, and those that do exist only slightly reduce symptoms, even after several clinical studies. The formation of Aβ plaques, neuroinflammation, and hyperphosphorylated tau neurofibrillary tangles are the characteristics of AD. While monoclonal antibodies such as lecanemab, donanemab, and aducanumab have demonstrated potential in addressing Aβ, their clinical efficacy and safety over an extended period of time remain uncertain. Novel avenues for tackling the underlying genetic causes of AD have been made possible by developments in genome editing tools, most notably CRISPR-Cas9. In preclinical animals, CRISPR-Cas9 has effectively edited genes relevant to AD, such as APP and PSEN1, leading to decreased levels of Aβ and enhanced cognitive function. Additionally, base and prime editing, two precision gene-editing techniques, have increased the medicines' selectivity and decreased their offtarget effects. However, before clinical applications are deployed, challenges related to technology, ethics, and safety must be resolved. This review highlights how monoclonal antibodies, neuroinflammation research, and CRISPR-Cas9 have the potential to revolutionize therapy choices for AD by examining the most current developments in the field.},
}

@article {pmid41941283,
year = {2026},
author = {Natarajan, J and Ranganathan, S},
title = {Hydrogel-forming Microneedles: A Next-generation Approach for Enhanced Dermal Drug Delivery in Alzheimer's and Neurological Disorders.},
journal = {Central nervous system agents in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715249400208251205125114},
pmid = {41941283},
issn = {1875-6166},
abstract = {Hydrogel-Forming Microneedles (HFMNs) offer a minimally invasive, patient-friendly, and sustained-release platform for transdermal delivery. By swelling upon insertion to form a hydrogel matrix, they enable efficient delivery of small molecules, biologics, and nanoparticles while bypassing gastrointestinal degradation and first-pass metabolism. In neurological disorders such as Alzheimer's and Parkinson's disease, they can improve bioavailability and overcome Blood-Brain Barrier (BBB) restrictions. However, limitations remain, including limited macromolecule payload, variable skin penetration, and regulatory challenges. To critically review recent progress in HFMNs for neurological drug delivery and assess their translational readiness. The objective is to evaluate advances in design, materials, fabrication, and therapeutic applications, and identify key challenges and future prospects. A literature review (2018-2024) covering polymer selection, crosslinking strategies, smart-material integration, and CNS-targeted applications. HFMNs successfully deliver donepezil, memantine, rivastigmine, and neurotrophic factors, achieving sustained release, improved bioavailability, and enhanced patient compliance. Smart HFMNs with biosensors and nanocarriers show improved BBB penetration. HFMNs represent a promising alternative to conventional CNS drug delivery. Addressing payload, penetration consistency, and scalable manufacturing will be vital for clinical adoption.},
}

@article {pmid41941323,
year = {2026},
author = {Marselli, G and Corbo, I and Pecchinenda, A and Forte, G and Favieri, F and Troisi, G and Blasutto, B and Casagrande, M},
title = {Emotional-cognitive integration in aging: the role of alexithymia in mild cognitive impairment.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1737901},
doi = {10.3389/fpubh.2026.1737901},
pmid = {41941323},
issn = {2296-2565},
mesh = {Humans ; *Cognitive Dysfunction/psychology ; *Affective Symptoms/psychology ; Aged ; Female ; Male ; Middle Aged ; Aged, 80 and over ; *Aging/psychology ; Neuropsychological Tests ; *Cognition ; *Emotions ; },
abstract = {INTRODUCTION: Aging is accompanied by a range of cognitive and emotional changes. Among these, difficulty in identifying and describing feelings and a tendency toward externally oriented thinking have been associated with frank cognitive decline. This pattern is known as alexithymia and reflects emotional dysregulation. Research Questions-This study aimed to investigate the largely unexplored relationship between alexithymia and cognitive functioning in older adults within the context of mild cognitive impairment (MCI).

METHODS: Three hundred and twenty adults aged 50-80 years classified as healthy controls, amnestic MCI (aMCI), or non-amnestic MCI (naMCI), completed a comprehensive neuropsychological assessment and the 20-item Toronto Alexithymia Scale (TAS-20).

RESULTS AND DISCUSSION: Participants with aMCI showed significantly higher levels of alexithymia, compared to healthy controls. This pattern suggests that emotional dysregulation is more pronounced in individuals with memory-related cognitive decline. In both the aMCI and naMCI groups, correlations between alexithymia scores and cognitive measures were negative, indicating that higher alexithymia was associated with poorer cognitive performance. In contrast, these associations were weak in healthy controls, implying that the link between emotional processing difficulties and cognitive inefficiency emerges primarily in MCI. Taken together, these findings point to a specific interplay between emotional and cognitive domains in the early stages of neurodegenerative decline. Accordingly, elevated alexithymia in aMCI individuals might represent a socio-emotional marker of prodromal Alzheimer's disease, highlighting the importance of considering emotional regulation in the assessment of cognitive aging.},
}

Humans
*Cognitive Dysfunction/psychology
*Affective Symptoms/psychology
Aged
Female
Male
Middle Aged
Aged, 80 and over
*Aging/psychology
Neuropsychological Tests
*Cognition
*Emotions

@article {pmid41941399,
year = {2026},
author = {, },
title = {Correction: Exploring emotion recognition in patients with mild cognitive impairment and Alzheimer's dementia undergoing a rehabilitation program emotion recognition in patients with dementia.},
journal = {PloS one},
volume = {21},
number = {4},
pages = {e0346658},
doi = {10.1371/journal.pone.0346658},
pmid = {41941399},
issn = {1932-6203},
abstract = {[This corrects the article DOI: 10.1371/journal.pone.0322213.].},
}

@article {pmid41941495,
year = {2026},
author = {Taniguchi, N and Ohkawa, Y and Nakano, M and Gu, J and Takahashi, M},
title = {The Role of Glycans and Glycosyltransferases Involved in N-glycan Branching in Cancer, COPD, Alzheimer's Disease, and Redox Regulation.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {229},
pages = {},
doi = {10.3791/69958},
pmid = {41941495},
issn = {1940-087X},
mesh = {*Alzheimer Disease/metabolism/enzymology ; Animals ; *Glycosyltransferases/metabolism ; *Polysaccharides/metabolism/biosynthesis/chemistry ; Mice ; *Pulmonary Disease, Chronic Obstructive/metabolism/enzymology ; Oxidation-Reduction ; *Neoplasms/metabolism/enzymology ; Humans ; },
abstract = {Glycosyltransferases that biosynthesize glycans and their genes (glycogenes) play important roles in health and disease. In general, pathophysiological changes are defined by comparing knock-out (KO) or knock-in mice generated using CRISPR-Cas9 and other technologies to normal mice. Next, target molecules such as glycoproteins, glycolipids, and proteoglycans to which various biosynthetic glycans bind were identified. As a result, we found that N-glycan branches biosynthesized by glycosyltransferases are intrinsically involved in Alzheimer's disease, cancer metastasis, epithelial mesenchymal transition (EMT)/mesenchymal epithelial transition (MET), type 2 diabetes, chronic obstructive pulmonary disease (COPD), and ulcerative colitis. For example, the addition of core fucose biosynthesized by α1,6-fucosyltransferase (Fut8) leads to dysregulation of TGF-β receptors. Bisecting N-acetylglucosamine (GlcNAc) biosynthesized by β-1,4-GlcNAc transferase III (GnT-III) affects the subcellular localization of Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 (β-secretase 1, referred to as BACE1). β1,6GlcNAc branching biosynthesized by GnT-V leads to the modification of matrix metalloproteinase (MMP). Identification and characterization of N-glycan structures on these proteins were performed using a glycoproteomic approach based on lectin blotting, western blotting, liquid chromatography-electron spray ionization mass spectrometry, and histochemical staining. Recently, studies concerning redox regulation of N-glycans, termed Glyco-Redox, have emerged as a promising approach. Functional and pathophysiological glycan studies are one of the main goals of glycobiology research. In this review, we describe the role of N-glycan branching glycosyltransferases and their biosynthesized glycans in relation to various diseases, such as cancer metastasis, COPD, Alzheimer's disease, and ulcerative colitis.},
}

*Alzheimer Disease/metabolism/enzymology
Animals
*Glycosyltransferases/metabolism
*Polysaccharides/metabolism/biosynthesis/chemistry
Mice
*Pulmonary Disease, Chronic Obstructive/metabolism/enzymology
Oxidation-Reduction
*Neoplasms/metabolism/enzymology
Humans

@article {pmid41941608,
year = {2026},
author = {Wang, T and Sun, Y and Lin, YR and Yao, L and Qiang, W},
title = {Controlled Seeding of β-Amyloid Fibrillation Reveals Propagation of Structural Polymorphisms in Cellular Environments.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.6c00013},
pmid = {41941608},
issn = {1520-4995},
abstract = {Molecular-level structural polymorphisms of β-amyloid (Aβ) aggregates in Alzheimer's disease patients are pathologically important. However, tracking the propagation and modulation of Aβ structural polymorphisms via ex vivo approaches remains challenging. The successful application of cryogenic transmission electron microscopy (cryo-TEM) in this area relies on the availability of morphologically distinct micrographs, which then enable unambiguous three-dimensional structural reconstruction of individual fibrillar polymorphs to achieve optimal resolution. As a complementary approach, solid-state nuclear magnetic resonance (ssNMR) spectroscopy with guided isotope-labeling schemes can provide site-specific and quantitative information on the populations of individual polymorphs. Such ssNMR sample preparations require ex vivo seeding, in which key parameters─including seed concentration and seeding time─must be carefully controlled for individual Aβ-cell systems to avoid the introduction of self-nucleated fibrillar polymorphs. In this work, we show that the application of controlled ex vivo seeding combined with quantitative ssNMR spectroscopy reveals the propagation of molecular-level structural polymorphs, depending on the types of seeds and cells.},
}

@article {pmid41941651,
year = {2026},
author = {Colwell, CS},
title = {Timing the decline: Cellular circadian rhythms and Alzheimer's disease.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {15},
pages = {e2604049123},
doi = {10.1073/pnas.2604049123},
pmid = {41941651},
issn = {1091-6490},
}

@article {pmid41941947,
year = {2026},
author = {Srilakshmi, V and Devarasetty, P and Chetana, VL and Vinta, S and Kowtharapu, R},
title = {Alzheimer's Disease Staging Using Enhanced Inception-ResNet-V2 and Improved XceptionNet Models for 3D MRI Classification and Segmentation.},
journal = {Journal of neuroscience methods},
volume = {},
number = {},
pages = {110767},
doi = {10.1016/j.jneumeth.2026.110767},
pmid = {41941947},
issn = {1872-678X},
abstract = {BACKGROUND: Neurologists have a significant challenge due to the progressive nature of Alzheimer's disease (AD) and its severe effects on cognitive function. Recent advances in neuroimage analysis have opened the door to novel machine-learning techniques that could greatly improve AD diagnosis, progression prediction, and detection.

NEW METHOD: In this research, we provide an enhanced hybrid deep learning approach for combined AD classification and segmentation. An enhanced inception-ResNet-V2 model is used for the multi-class classification of AD and an improved XceptionNet model is used to segment affected brain region of AD. The spatial features present in 3D MRI scans are effectively extracted by the parallel convolutional neural network (PCNN) model.

RESULTS: The OASIS and ADNI datasets were used in this research to detect and classify the AD stage. The proposed approach yielded consistently excellent testing accuracy and outstanding training accuracy. For testing, a higher accuracy of 99.5% for the OASIS dataset and 99.7% for the ADNI dataset is attained using the proposed approach.

Based on 3D MRI brain scans, these results demonstrate the exceptional ability of the proposed models, especially the Improved XceptionNet, to identify AD reliably. Based on the findings of the experiment, the proposed model outperforms cutting-edge deep learning models for classification and segmentation.

CONCLUSIONS: The experimental results show that incorporating advanced architectures significantly improves the precision of detecting and assessing brain changes associated with AD, offering practical tools for early diagnosis and monitoring the disease naturally.},
}

@article {pmid41941989,
year = {2026},
author = {Sun, Z and Peng, Q and Qiu, C and Jia, X and Wang, H and Wu, S and Tao, W},
title = {A specific Pilose antler peptide LVLVEAELRE ameliorates cognitive deficits in SAMP8 mice via Celsr2.},
journal = {Journal of ethnopharmacology},
volume = {},
number = {},
pages = {121649},
doi = {10.1016/j.jep.2026.121649},
pmid = {41941989},
issn = {1872-7573},
abstract = {Pilose antler peptide (PAP), an extract derived from the traditional Chinese medicinal material Pilose antler, has shown promise in the treatment of neurodegenerative diseases. However, the precise molecular mechanisms underlying its anti-Alzheimer's disease (AD) effects remain to be fully elucidated.

AIM OF THE STUDY: This study focuses on a specific PAP monomer with a defined sequence (LVLVEAELRE), herein referred to as PAP, to explore its potential role and molecular mechanisms in AD treatment.

MATERIALS AND METHODS: Senescence-accelerated mouse prone 8 (SAMP8) mice were employed to evaluate the effects of PAP on cognitive function, classical AD pathologies (Aβ and p-Tau), and synaptic plasticity. To further elucidate the causal role of Cadherin EGF LAG seven-pass G-type receptor 2 (Celsr2), bidirectional viral manipulations (AAV-shCelsr2 for knockdown and AAV-OECelsr2 for overexpression) were performed in vivo. Furthermore, cellular thermal shift assays (CETSA), molecular docking, and microscale thermophoresis (MST) were utilized to validate the direct interaction between PAP and Celsr2.

RESULTS: PAP administration significantly improved cognitive impairment, mitigated Aβ deposition and Tau hyperphosphorylation, and enhanced synaptic plasticity in SAMP8 mice. Mechanistically, PAP upregulated Celsr2 expression, restored AMPA receptor subunits, and inhibited neuronal senescence. Crucially, Celsr2 knockdown abolished these neuroprotective benefits, whereas Celsr2 overexpression synergistically amplified the therapeutic efficacy of PAP. Finally, MST and docking analyses confirmed that PAP possesses a high and specific binding affinity for WT Celsr2.

CONCLUSIONS: This study demonstrates that PAP ameliorates AD-like pathology by regulating Celsr2, highlighting its potential as a promising preclinical drug candidate. The research findings provide a theoretical basis for the development of PAP-based therapeutic strategies for Alzheimer's disease.},
}

@article {pmid41941996,
year = {2026},
author = {Wagner, S and Danz, K and Hyvärinen, J and Fischer, AL and Kanninen, KM and Gynther, M and Puris, E},
title = {Characterisation of a patient-derived iPSC-based model for studying the blood-brain barrier in Alzheimer's disease.},
journal = {Brain research bulletin},
volume = {},
number = {},
pages = {111872},
doi = {10.1016/j.brainresbull.2026.111872},
pmid = {41941996},
issn = {1873-2747},
abstract = {The blood-brain barrier (BBB) comprised of the brain capillary endothelial cells (BCECs), with its tight junctions (TJ), transporters and receptors, regulates the passage of solutes, such as nutrients, metabolites, and xenobiotics, including drugs. In Alzheimer's disease (AD), characterised by the accumulation of amyloid-β peptide (Aβ) and the formation of hyperphosphorylated tau aggregates, a compromised BBB integrity was reported. There is a lack of knowledge about the effects of tau pathology on BBB function in AD. Advances in developing BBB models using human induced pluripotent stem cell (hiPSC)-derived BCECs have opened a new avenue for investigating AD-related changes in BBB functional integrity. Here, we characterised the BBB model derived from hiPSCs generated from an AD patient with a tau-related mutation (STBCi 062-A) versus the one based on a healthy person's cells (UKKi 011-A) in terms of mimicking AD-related changes in paracellular permeability, TJs, transporters, receptors and other proteins playing a role in BBB integrity. The STBCi 062-A-derived BCECs showed lower TEER values and increased permeability associated with downregulation of proteins regulating TJ organization and BBB integrity, as compared to UKKi 011-A-derived BCECs. We revealed AD-relevant increase in protein expression of efflux transporter BCRP and amino acid transporter ASCT1, as well as transferrin receptor protein 1 in the STBCi 062-A-derived BCECs compared to UKKi 011-A-derived BCECs. The developed AD-patient-hiPSC-derived BCEC model possesses several important characteristics that recapitulate changes in BBB integrity in AD and can serve as a robust tool for developing AD treatments.},
}

@article {pmid41942124,
year = {2026},
author = {Liu, Z and Ai, Y and Wu, Y and Zhang, Y and Hua, J and Liu, T and Liu, D and Chen, GC and Xu, G and Chen, LH},
title = {Association of circulating branched-chain or aromatic amino acids based on metabolome and apolipoprotein E genotype with incident dementia: a large cohort study.},
journal = {International journal of food sciences and nutrition},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/09637486.2026.2649766},
pmid = {41942124},
issn = {1465-3478},
abstract = {The associations between branched-chain amino acids (BCAAs) and dementia in individuals with chronic diseases remain unclear, and evidence on aromatic amino acids (AAAs) is limited. Using metabolic biomarker data from 117,892 UK Biobank participants, we found that higher circulating levels of BCAAs (HR=0.56, 95% CI: 0.41-0.76) and AAAs (HR=0.74, 95% CI: 0.55-0.98) were associated with lower risks of all-cause dementia and Alzheimer's disease, but not vascular dementia. Stratified analyses showed stronger inverse associations for BCAAs among women and individuals without diabetes (both P for interaction = 0.001). Similarly, AAAs were inversely associated with dementia risk primarily in non-diabetic participants, but not modified by hypertension or dyslipidemia. These findings highlight the potential protective roles of BCAAs and AAAs and underscore the importance of sex and diabetes status in dementia prevention.},
}