@article {pmid41968216,
year = {2026},
author = {Zhu, S and Li, Y and Lin, C and Liu, X and Luo, Y and Qian, H and Tang, Z},
title = {Combined with network pharmacology, the therapeutic effect and mechanism of coumarins from Chimonanthus praecox extract in the treatment of Alzheimer's disease were investigated.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {41968216},
issn = {1432-1912},
support = {grant number 82360873//National Natural Science Foundation General Project/ ; No: Qiankeheji-ZK [2022]- General 471//Guizhou Provincial Department of Science and Technology Project/ ; Contract No.: YCXKYB2023017//Construction Task of Graduate Education Innovation Plan Project of Guizhou University of Traditional Chinese Medicine/ ; },
abstract = {The objective of this study is to investigate the therapeutic potential and underlying mechanisms of Chimonanthus praecox-derived coumarins in Alzheimer's disease (AD)-related neuroinflammatory and cognitive impairments. Network pharmacology was employed to identify active components and targets of Chimonanthus praecox-derived coumarins, followed by intersection analysis with AD-related genes. A protein-protein interaction (PPI) network was constructed and subjected to functional enrichment analysis. Molecular docking was performed to validate the binding affinity between key compounds and core targets. An AD-like rat model characterized by aging-related cognitive impairment and neuroinflammation was established using D-galactose and aluminum chloride, and therapeutic effects of coumarin treatment were evaluated via behavioral testing, HE staining, immunohistochemistry, Western blotting, and electroencephalography (EEG). Four active compounds, 58 drug targets, and 19 AD-related intersecting targets were identified, primarily enriched in neuroinflammation-related pathways including NF-κB p65, NLRP3, and Alzheimer's disease-related pathways. Molecular docking showed strong binding of key coumarin derivatives to amyloid precursor protein (APP), apolipoprotein E4 (APOE4), NF-κB p65, and prostaglandin-endoperoxide synthase 2 (PTGS2). In vivo, Chimonanthus praecox-derived coumarin treatment improved aging-associated cognitive deficits, alleviated hippocampal neuronal injury, inhibited APP and APOE4 expression, and significantly downregulated NF-κB p65, PTGS2, IL-6, and NLRP3 levels. EEG analysis further confirmed attenuation of abnormal neural activity. Chimonanthus praecox-derived coumarins exert neuroprotective and anti-inflammatory effects through multi-target modulation, supporting their potential as candidate agents for AD-related neuroinflammatory and cognitive dysfunction.},
}

@article {pmid41968260,
year = {2026},
author = {Zhan, M and Liu, G and Liu, YM and Wang, B},
title = {Up-regulation of miR-548 m Leading to Neuroinflammation to Promote the Progression of Alzheimer's Disease.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
pages = {},
pmid = {41968260},
issn = {1559-1182},
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Alzheimer Disease/genetics/pathology/metabolism ; Male ; *Up-Regulation/genetics ; Microglia/metabolism/pathology ; *Neuroinflammatory Diseases/genetics/pathology/metabolism ; *Disease Progression ; Mice, Transgenic ; Mice ; Mice, Inbred C57BL ; Cytokines/metabolism ; },
abstract = {Neuroinflammation mediated by microglia is recognized as a critical contributor to Alzheimer's disease (AD) pathogenesis, and P2RY12 maintains microglial homeostasis. MicroRNAs regulate gene expression post-transcriptionally and have been implicated in modulating microglial activation states during AD by affecting inflammatory pathways. This study aimed to investigate the role of miR-548 m in regulating microglial polarization and neuroinflammation in Alzheimer's disease. Male APP/PS1 transgenic and wild-type mice were utilized as animal models alongside cultured microglial cells for in vitro studies. Behavioral assessments, including contextual fear Morris water maze (MWM) and fear conditioning (FC), evaluated cognitive function. Molecular analyses comprised RT-qPCR western blot, and ELISA, as well as dual-luciferase reporter assays to validate miR-548 m and P2RY12 interactions. In vivo modulation of miR-548 m expression was achieved via stereotaxic intracerebral injections of agomir or antagomir oligonucleotides targeting the dentate gyrus. MiR-548 m was significantly upregulated in AD. Overexpression of miR-548 m promoted microglial M1 polarization characterized by increased pro-inflammatory cytokines (TNF-α, IL-6, iNOS, IL-1β) and reduction in M2 anti-inflammatory markers (Arg1, CD206, IL-4, TGF-β). Inhibition of miR-548 m improved spatial learning and memory performance while attenuating microglial activation in vivo. Luciferase reporter assays confirmed that P2RY12 is a direct downstream target suppressed by miR-548 m. And overexpression of miR‑548 m reversed the inflammatory effects induced by P2RY12 overexpression. These findings demonstrate that elevated miR‑548 m exacerbates neuroinflammation through negative regulation of P2RY12 expression, leading to enhanced microglial M1 polarization during AD progression. Targeting the miR‑548 m/P2RY12 axis may provide a novel therapeutic for mitigating AD.},
}

*MicroRNAs/genetics/metabolism
Animals
*Alzheimer Disease/genetics/pathology/metabolism
Male
*Up-Regulation/genetics
Microglia/metabolism/pathology
*Neuroinflammatory Diseases/genetics/pathology/metabolism
*Disease Progression
Mice, Transgenic
Mice
Mice, Inbred C57BL
Cytokines/metabolism

@article {pmid41968275,
year = {2026},
author = {Moon, J and Kim, S and Chung, H and Jang, I and , },
title = {Cyclic 2.5D Perceptual Loss for Cross-Modal 3D Medical Image Synthesis: T1w MRI to Tau PET.},
journal = {Human brain mapping},
volume = {47},
number = {5},
pages = {e70508},
doi = {10.1002/hbm.70508},
pmid = {41968275},
issn = {1097-0193},
support = {RS-2024-00455720//National Research Foundation of Korea (NRF), Ministry of Science and ICT (MSIT)/ ; RS-2024-00414119//National Research Foundation of Korea (NRF), Ministry of Science and ICT (MSIT)/ ; RS-2024-00338048//National Research Foundation of Korea (NRF), Ministry of Science and ICT (MSIT)/ ; 2024ER040700//Korea National Institute of Health (KNIH)/ ; 2025ER040300//Korea National Institute of Health (KNIH)/ ; RS-2025-13002970//Ministry of Trade, Industry and Energy (MOTIE)/ ; RS-2025-02220534//Korea Health Industry Development Institute (KHIDI), Ministry of Health & Welfare (MOHW)/ ; //Hankuk University of Foreign Studies Research Fund of 2025/ ; RS-2024-00412644//Institute for Information & Communication Technology Planning & Evaluation (IITP), Ministry of Science and ICT (MSIT)/ ; IITP-(2025)-RS-2023-00253914//Institute for Information & Communication Technology Planning & Evaluation (IITP), Ministry of Science and ICT (MSIT)/ ; RS-2024-00332210//Korea Creative Content Agency (KOCCA), Ministry of Culture, Sports and Tourism (MCST)/ ; RS-2020-II201373//Artificial Intelligence Graduate School Program (Hanyang University), Ministry of Science and ICT (MSIT)/ ; RS-2023-00261368//Artificial Intelligence Graduate School Program (Hanyang University), Ministry of Science and ICT (MSIT)/ ; KSC-2025-CRE-0065//National Supercomputing Center, Korea Institute of Science and Technology Information/ ; KSC-2024-CRE-0021//National Supercomputing Center, Korea Institute of Science and Technology Information/ ; },
mesh = {Humans ; *Positron-Emission Tomography/methods/standards ; *Magnetic Resonance Imaging/methods/standards ; *tau Proteins/metabolism ; *Imaging, Three-Dimensional/methods/standards ; *Alzheimer Disease/diagnostic imaging/metabolism ; *Neuroimaging/methods/standards ; Male ; Female ; Aged ; *Brain/diagnostic imaging/metabolism ; },
abstract = {Positron emission tomography (PET) provides an in vivo molecular marker for various diseases, including Alzheimer's disease and related dementias (ADRD). PET has become increasingly integrated into diagnostic decision-making, disease staging, and clinical trial enrichment. However, its widespread use remains constrained by high costs, government regulations, and the invasiveness of radiotracer injection. Modern diagnostic frameworks emphasize the importance of multimodal biomarker assessment, such as the "amyloid/tau/neurodegeneration" (A/T/N) framework for Alzheimer's disease; however, they are constrained by these barriers. Medical image synthesis or translation offers a potential solution by enabling the reconstruction of unavailable modalities. The clinical utility of PET depends on accurately capturing regional uptake patterns rather than exact voxel-wise intensities, motivating the use of perceptual loss functions to assess higher-level semantic features in generative models. While 2D, 3D, and 2.5D perceptual losses are utilized in 3D synthesis, each encounters challenges, including limited volumetric context, the scarcity of pretrained 3D models, and difficulty balancing optimization across anatomical planes. In this work, we address cross-modal synthesis of tau PET from structural magnetic resonance imaging (MRI), generating 3D pseudo-[[18]F]flortaucipir standardized uptake value ratio (SUVR) maps from 3D T1-weighted MR images. We propose a cyclic 2.5D perceptual loss that cyclically optimizes the axial, coronal, and sagittal planes over training phases, thereby enhancing volumetric consistency. Furthermore, we standardize PET SUVRs by scanner manufacturer, reducing inter-manufacturer variability and better preserving high-uptake regions. We evaluate the proposed approach on cohorts spanning the ADRD spectrum using data from the Alzheimer's Disease Neuroimaging Initiative and the Standardized Centralized Alzheimer's Disease and Related Dementias Neuroimaging cohort. Our approach is broadly applicable across various generative frameworks and achieves high quantitative and qualitative performance on diverse architectures, including U-Net, UNETR, SwinUNETR, CycleGAN, and Pix2Pix. Notably, it achieves better agreement between synthesized SUVRs and measured PET scans in key brain regions relevant to Alzheimer-type tau pathology. The code is publicly available at https://github.com/labhai/Cyclic-2.5D-Perceptual-Loss.},
}

Humans
*Positron-Emission Tomography/methods/standards
*Magnetic Resonance Imaging/methods/standards
*tau Proteins/metabolism
*Imaging, Three-Dimensional/methods/standards
*Alzheimer Disease/diagnostic imaging/metabolism
*Neuroimaging/methods/standards
Male
Female
Aged
*Brain/diagnostic imaging/metabolism

@article {pmid41968284,
year = {2026},
author = {Kim, Y and Lee, BH and Ahn, B and Ko, EA and Kang, D},
title = {Microglia-Specific K2P Channel THIK-1: Structure, Function, and Therapeutic Potential.},
journal = {Acta physiologica (Oxford, England)},
volume = {242},
number = {5},
pages = {e70224},
doi = {10.1111/apha.70224},
pmid = {41968284},
issn = {1748-1716},
mesh = {Humans ; *Microglia/metabolism ; *Potassium Channels, Tandem Pore Domain/metabolism/chemistry ; Animals ; Potassium Channels ; },
abstract = {BACKGROUND: The tandem pore domain halothane-inhibited potassium (THIK-1) channel is a member of the two-pore domain potassium (K2P) channel family and plays a critical role in maintaining the resting membrane potential. THIK-1 has emerged as a key regulator of microglial physiology and neuroimmune signaling. With the rapid accumulation of structural, electrophysiological, and functional evidence, there is an increasing need for an integrated understanding of THIK-1 in the context of microglial biology and disease.

AIMS: This review provides a comprehensive synthesis of the structural, regulatory, and functional properties of THIK-1, with a particular focus on its roles in microglial physiology, neuroimmune signaling, and central nervous system (CNS) pathologies.

MATERIALS AND METHODS: We conducted a comprehensive review of recent literature, including electrophysiological, molecular, and structural studies, with particular emphasis on cryo-electron microscopy findings, pharmacological modulation, and disease-associated functional analyses.

RESULTS: THIK-1 is selectively enriched in microglia and contributes to essential cellular processes, including surveillance motility, synaptic pruning, and inflammasome activation. Its high constitutive activity makes it a dominant determinant of the microglial membrane potential. Structural studies have identified key features, including a lipid-interacting pocket and a cytoplasmic gate, which underlie lipid- and anesthetic-mediated regulation. Functionally, THIK-1-mediated K⁺ efflux is required for NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation and pyroptosis. Accumulating evidence links THIK-1 to major CNS disorders, including neuroinflammation, neurodegeneration (e.g., Alzheimer's and Parkinson's diseases), and psychiatric disorders.

DISCUSSION: The convergence of structural, electrophysiological, and immunological findings positions THIK-1 as a central regulator of neuroimmune signaling. Integration of these findings provides new insights into how ion channel activity shapes microglial function and disease processes.

CONCLUSION: THIK-1 represents a critical nexus between ion channel biophysics and neuroimmune dysfunction. A comprehensive understanding of its regulation and function supports its potential as a microglia-specific therapeutic target in neuroinflammatory and neurodegenerative disorders.},
}

Humans
*Microglia/metabolism
*Potassium Channels, Tandem Pore Domain/metabolism/chemistry
Animals
Potassium Channels

@article {pmid41968555,
year = {2026},
author = {Kaur, K and Goel, H and Chawla, PA and Chawla, V},
title = {Trends and Perspectives in the Targeting of Brain Through Ethosomal Formulations.},
journal = {Recent advances in drug delivery and formulation},
volume = {},
number = {},
pages = {},
doi = {10.2174/0126673878418338251203100909},
pmid = {41968555},
issn = {2667-3886},
abstract = {Neurological diseases such as Alzheimer's disease, Schizophrenia, anxiety, Parkinson's disease, and migraine are serious conditions that continue to threaten mankind. The cases of brainrelated disorders are increasing worldwide and are closely related to physiological, genetic, and environmental factors. Direct drug delivery to the brain is crucial for the effective treatment and prevention of these conditions. However, due to the presence of a lipophilic barrier, i.e., the bloodbrain barrier, the entry of therapeutic agents into the brain is restricted, resulting in a lower concentration at the targeted site. As a solution to this problem, the direct nose-to-brain connection is attracting attention for its effective, precise, non-invasive delivery of drugs via the olfactory and trigeminal pathways. However, there are some limitations, like permeability across the nasal mucosa and mucociliary clearance. Therefore, to overcome these restrictions, the use of nanocarriers, particularly ethosomes, is being attempted. This review paper delves into recent research papers and reports on ethosomes developed for intranasal delivery towards the management of neurological conditions. Ethosomes demonstrated an exceptional capacity to facilitate drug accumulation at targeted sites, owing to their ability to bypass first-pass metabolism, their flexible nature, and the presence of penetration enhancers. The high ethanol content in the composition significantly increases the fluidity of the lipid bilayer, allowing for better interaction of this vesicular system with the blood-brain barrier. Furthermore, the functionalization of ethosomes can enhance the specific delivery of drugs, increase patient compliance, and minimize side effects. However, no intranasal ethosomes for direct brain delivery have progressed from preclinical testing to the bedside of patients. They are still in the experimental phase, particularly in animals or in vivo lab models. The possibilities of toxic effects, the use of high amounts of ethanol, and irregular nasal absorption are a few concerns that need to be addressed. The increasing demand for intranasal delivery suggests that ethosomes may play a pivotal role in the management and treatment of brain-related conditions, but this will only occur after a substantial number of clinical trials confirm their safety and efficacy for human consumption. This review explores such possibilities and highlights current trends and future perspectives in targeting the brain with ethosomal formulations.},
}

@article {pmid41968642,
year = {2026},
author = {Winford, ED and Huber, BD and Seblova, D and Pyne, J and Avila-Rieger, JF and Turney, IC and Mazen, JA and Brickman, AM and Manly, JJ},
title = {Associations between parental history of dementia and plasma markers of inflammation in a multi-ethnic middle-aged community of adults.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71355},
doi = {10.1002/alz.71355},
pmid = {41968642},
issn = {1552-5279},
support = {R01AG054070/AG/NIA NIH HHS/United States ; //Burroughs Wellcome Fund Postdoctoral Diversity Enrichment Program (PEDP)/ ; AARF-21-848200/ALZ/Alzheimer's Association/United States ; 22/MED/012//PRIMUS Research Programme/ ; UL1R001873//National Center for Advancing Translational Sciences, National Institutes of Health/ ; },
mesh = {Humans ; Female ; Male ; *Dementia/genetics/blood/ethnology ; Middle Aged ; Biomarkers/blood ; *Inflammation/blood/genetics/ethnology ; *Cytokines/blood ; *Parents ; Ethnicity ; Aged ; },
abstract = {INTRODUCTION: Parental history of dementia is associated with increased dementia risk. We investigated whether having a parent with dementia is associated with increased peripheral inflammation in middle-aged adults.

METHODS: Participants were from the Offspring Study (n = 1204). Parental dementia status was determined by a diagnostic consensus conference. Plasma chemokine and cytokine concentrations were assayed with Luminex technology.

RESULTS: Parental history of dementia was associated with higher levels of eotaxin and lower levels of granulocyte colony-stimulating factor, vascular endothelial growth factor A, and interleukin (IL)-27. IL-18 and epidermal growth factor levels were higher in Black individuals with a parental history of dementia compared to Hispanic individuals with the same history. Women with a parental history of dementia had higher levels of interferon-alpha 2, IL-12p70, soluble CD40 ligand, and IL-18 compared to men with the same history.

DISCUSSION: Parental history of dementia is associated with elevated markers of peripheral inflammation. These associations vary across sex, race, and ethnicity.},
}

Humans
Female
Male
*Dementia/genetics/blood/ethnology
Middle Aged
Biomarkers/blood
*Inflammation/blood/genetics/ethnology
*Cytokines/blood
*Parents
Ethnicity
Aged

@article {pmid41968685,
year = {2026},
author = {Zeng, J and Wang, P and Fan, Z and Wang, G and Zhou, J and Zhang, F},
title = {Chlorogenic Acid: Characteristics, Neuroprotective Effects, and Potential Mechanisms.},
journal = {Current neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/011570159X459115260204170117},
pmid = {41968685},
issn = {1875-6190},
abstract = {In this review, we explore recent evidence connecting chlorogenic acid (CGA) to neuropsychiatric disorders and critically discuss the biological mechanisms underlying these effects. CGA is a natural polyphenol that usually exists in fruits and vegetables. CGA has long been recommended for its broad pharmacological activities. Increasing evidence from animal studies has revealed that dietary CGA supplementation may confer protective effects on the nervous system. Here, we summarize multiple findings on CGA in animal models of neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, stroke, depression, epilepsy, and other neuropsychiatric disorders. We place equal emphasis on chemical features, natural sources, bioavailability, and pharmacological properties of CGA; all of these can have a critical impact on CGA's intervention. Current experimental evidences suggest that the neuroprotective effects of CGA are driven by the convergence of several processes, including suppression of neuroinflammation, attenuation of oxidative stress, and context-dependent effects on synaptic and cellular homeostasis. In some models, CGA has also been associated with changes in autophagic activity and reduced accumulation of misfolded or aggregated proteins. Despite these advances, the field still lacks a coherent molecular framework that links CGA exposure to specific neural outcomes. Therefore, resolving this gap will be essential for the clinical application of CGA.},
}

@article {pmid41968748,
year = {2026},
author = {Hilpert, K},
title = {Peptidomics: A New Dimension in Microbiome Research.},
journal = {Protein and peptide letters},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298665436241260327111926},
pmid = {41968748},
issn = {1875-5305},
abstract = {The human gut microbiome is now recognised as a major determinant of health, with roles extending beyond digestion to influence neurodegeneration, metabolism, immunity, and pharmacological responses. Clinical studies link microbial imbalances to Alzheimer's disease, Parkinson's disease, depression, and cardiovascular disorders, yet the underlying mechanisms remain only partly understood. Methodological advances have progressively deepened our insight. DNA-based sequencing (metagenomics) catalogues microbial genes but reveals only potential functions. RNA-based sequencing (metatranscriptomics) highlights active gene expression, but instability of transcripts and poor correlation with protein activity limit its predictive value. Metabolomics measures small-molecule end products, providing direct evidence of microbial biochemistry and identifying disease-linked metabolites such as urolithin A, trimethylamine N-oxide, and equol. These approaches together have transformed microbiome science, but they remain incomplete. A critical and underutilised dimension is peptidomics: the systematic analysis of endogenous peptides in the gut and circulation. Enabled by peptide-enriching, protease-inhibiting workflows and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), peptidomics directly captures unstable signaling peptides and proteolytic fragments that are often invisible to conventional proteomics. Coupled with emerging gut-specific peptide databases, such as MetaPep, and Artificial Intelligence (AI) assisted de novo sequencing and spectral prediction for non-human peptides, this provides a concrete technical route to reading out the functional peptide layer of the microbiome. Peptidomics can capture functional signals of host-microbiome interaction, reveal context-specific biomarkers, and provide mechanistic insight into disease. Recent studies demonstrate that peptide-level resolution uncovers microbial contributions to gut inflammation, modulates the gut-brain axis, and enables peptide-based disease stratification in conditions such as inflammatory bowel disease. However, despite these promising examples, peptidomics remains largely absent from mainstream microbiome research, which needs to be changed. Integrating peptidomics with existing genomic, transcriptomic, and metabolomic approaches will generate a more complete and functional picture of the microbiome. This shift will accelerate biomarker discovery, refine diagnostics, and expand the search for peptide-based therapeutics, positioning peptidomics as an essential next step in microbiome science.},
}

@article {pmid41968970,
year = {2026},
author = {Massons, M and Guillen, N and Sarto, J and Falgàs, N and Borrego-Écija, S and Esteller-Gauxax, D and Castellví, M and Tort-Merino, A and Pérez-Millan, A and Antonell, A and Augè Fradera, JM and Piñol, G and Riba, I and Carnes-Vendrell, A and Cullell, M and Osuna, MT and Bajo, L and Romero, T and Bonjoch, E and Bello, J and Fernández, S and Balagué, M and Gómez-Ruiz, I and Boltes, A and Pont, C and Cuevas, R and Carrillo, S and Iglesias, L and Casadevall Codina, TM and Guinea, LG and Espada, FJ and Sánchez-Valle, R and Balasa, M and Lladó, A},
title = {Predictive Ability of Plasma p-tau217 for β-Amyloid Status: A Prospective Multicenter Study.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.70387},
pmid = {41968970},
issn = {2328-9503},
support = {CM23/00137//Instituto de Salud Carlos III/ ; JR22/00014//Instituto de Salud Carlos III/ ; AGAUR (SGR 2021-01126)//Fundació Societat Catalana de Neurologia, Generalitat de Catalunya/ ; },
abstract = {OBJECTIVE: Plasma tau phosphorylated at threonine 217 (p-tau217) measured with fully automated platforms has shown high accuracy for Alzheimer's disease (AD) diagnosis, but real-world multicenter data remain limited. We aimed to validate the diagnostic performance of p-tau217 for identifying AD pathology in a real-world multicenter cohort across seven memory clinics in Catalonia (Spain), with only one tertiary hospital with prior experience in AD blood-based biomarkers.

METHODS: In this prospective multicenter study, consecutive patients with cognitive impairment undergoing routine cerebrospinal fluid (CSF) biomarker testing were included. Plasma samples were collected following a standardized pre-analytical protocol and analyzed centrally using the Lumipulse G p-tau217 assay (Fujirebio). Diagnostic accuracy for Aβ status was assessed overall and across sites.

RESULTS: A total of 185 participants were included. Plasma p-tau217 showed excellent accuracy for CSF-defined Aβ status (AUC 0.916) with consistent performance across centers. Using a single cut-off, diagnostic accuracy reached 84.9%, which prompted the use of a dual-threshold strategy to improve overall performance and to classify p-tau217 values into low, intermediate, and high probability categories of Aβ positivity. When applying a strict model with 97.5% sensitivity and specificity (cut-offs 0.146/0.486 pg/mL), 42.7% of participants fell within the intermediate zone, whereas the remaining 57.3% were confidently classified with 95.3% accuracy.

INTERPRETATION: In a real-world multicenter memory-clinic cohort, plasma p-tau217 measured on a fully automated platform accurately discriminated CSF Aβ status and enabled reliable rule-in/rule-out classification in over half of patients. These findings support its broader clinical use as an initial diagnostic tool for AD.},
}

@article {pmid41969021,
year = {2026},
author = {Tran, D and Georgiadis, M and DiGiacomo, P and Nirschl, J and Cobos, I and Rosenberg, J and Edwards, N and Bone, S and Webb, S and Zeineh, M},
title = {Characterizing ferrous versus ferric iron in Alzheimer's disease using X-ray fluorescence imaging and XANES spectroscopy.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261435561},
doi = {10.1177/13872877261435561},
pmid = {41969021},
issn = {1875-8908},
abstract = {BackgroundThe accumulation of iron, such as ferrous Fe[2+], in the Alzheimer's disease (AD) brain may contribute to neurodegeneration by driving oxidative stress. While elevated iron in AD has been shown, the oxidation state of iron and its regional distribution in AD, particularly in the hippocampus, is unclear.ObjectiveTo characterize the oxidation state and spatial distribution of iron in the hippocampus of AD and control brains, and to assess the effect of tissue thawing on ferrous iron measurements.MethodsWe utilized X-ray fluorescence imaging and X-ray absorption near edge structure spectroscopy to localize and analyze iron deposition in fresh-frozen human hippocampal specimens stratified by AD disease stage. To assess the effect of thawing on iron oxidation, we used a cryo-chamber to keep three specimens frozen while their respective deposits were being scanned. These specimens were then allowed to thaw and their same deposits were rescanned for comparison.ResultsCompared to control brains, AD specimens exhibited elevated levels of ferrous iron (Fe[2][+]) in the cornu ammonis 1 (CA1)-subiculum subfields-regions known to degenerate early in AD. We also measured a decrease in Fe[2+] levels in AD and control specimens scanned after being thawed.ConclusionsOur findings support the association between elevated Fe[2+] and AD, consistent with existing hypotheses linking redox-active iron to oxidative stress and neuroinflammation. The observed reduction in Fe[2+] levels following thawing suggests that studies using thawed brain samples may underestimate Fe[2+] levels.},
}

@article {pmid41969035,
year = {2026},
author = {Shum, CK and Shea, YF and Au Yeung, TW and Chan, CCY and Chan, WC and Cheng, WK and Cheung, NYF and Cho, DHY and Chow, TK and Fong, GCY and Ip, BYM and Kwok, JSH and Lai, BMH and Lam, LCW and Lee, ATC and Lok, CM and Mok, KY and Ng, DKK and Siu, DYW and Yeung, PY and Tam, SKF},
title = {Consensus statement on the use of Alzheimer's disease biomarkers and anti-amyloid therapies in Hong Kong.},
journal = {Hong Kong medical journal = Xianggang yi xue za zhi},
volume = {},
number = {},
pages = {},
doi = {10.12809/hkmj2514198},
pmid = {41969035},
issn = {1024-2708},
abstract = {Alzheimer's disease (AD) is the most common aetiology of cognitive impairment worldwide and in Hong Kong. There have been rapid advances in the use of biomarkers for the diagnosis of AD and in the availability of anti-amyloid therapies (AAT) to slow cognitive and functional decline. At present, there is no consensus in Hong Kong regarding the application of AD biomarkers or the use of AAT. A multidisciplinary group of 20 medical specialists from five professional societies discussed issues related to the application of biomarkers for the diagnosis of AD pathology and the use of AAT, and reviewed the evidence in the context of local experience to inform recommendations. A modified Delphi approach was adopted to finalise the recommendations. Consensus was defined as ≥75% agreement on a 9-point Likert scale among panellists. The panel finalised 26 consensus statements addressing the use of AD biomarkers, including neuroimaging and fluid biomarkers, as well as the use of AAT, including inclusion criteria, serial neuroimaging monitoring during treatment, and management of infusion reactions. These recommendations are relevant to the Hong Kong healthcare setting and may serve as guidance for doctors across specialties to facilitate appropriate management of AD.},
}

@article {pmid41969120,
year = {2026},
author = {Izuo, N and Kondoh, H and Shimizu, T},
title = {Peripheral Insulin Resistance and Alzheimer's Disease: Possible Mediators Including Extracellular Vesicles.},
journal = {Geriatrics & gerontology international},
volume = {26},
number = {4},
pages = {e70483},
doi = {10.1111/ggi.70483},
pmid = {41969120},
issn = {1447-0594},
mesh = {Humans ; *Alzheimer Disease/metabolism/epidemiology/physiopathology/etiology ; *Insulin Resistance/physiology ; *Extracellular Vesicles/metabolism/physiology ; *Diabetes Mellitus, Type 2/metabolism/complications/epidemiology ; Animals ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; },
abstract = {Epidemiological studies consistently indicate that type 2 diabetes mellitus increases the risk of Alzheimer's disease (AD). Accumulating evidence suggests that insulin resistance, rather than hyperglycemia per se, is the principal metabolic factor associated with AD development. Population-based longitudinal studies show that insulin resistance is strongly linked to earlier amyloid β (Aβ) accumulation, whereas its association with tau pathology remains inconsistent. Importantly, insulin resistance-related cognitive decline and earlier disease onset cannot be fully explained by the extent of Aβ deposition alone, implying the involvement of additional pathogenic pathways. Animal studies further support a role for insulin resistance independent of sustained hyperglycemia. Genetic models of systemic insulin resistance demonstrate impairments in cognition, cerebral blood flow regulation, and emotional behavior, distinct from phenotypes observed in models with brain-specific disruption of insulin signaling. Together with clinical observations showing preserved central insulin responsiveness in individuals with type 2 diabetes, these findings highlight peripheral insulin resistance as a key contributor to brain vulnerability in AD. How peripheral insulin resistance influences the brain remains incompletely understood. Emerging evidence suggests that extracellular vesicles may act as a possible mediator of peripheral-central communication by conveying bioactive molecules across tissues. In this review, we summarize epidemiological and experimental evidence linking peripheral insulin resistance to AD and discuss the potential, yet still speculative, role of extracellular vesicles in this process.},
}

Humans
*Alzheimer Disease/metabolism/epidemiology/physiopathology/etiology
*Insulin Resistance/physiology
*Extracellular Vesicles/metabolism/physiology
*Diabetes Mellitus, Type 2/metabolism/complications/epidemiology
Animals
Amyloid beta-Peptides/metabolism
Brain/metabolism

@article {pmid41969246,
year = {2026},
author = {Jacques, RI and Paech, J and Gleason, A and de Souza, A},
title = {Posterior Cortical Atrophy Presenting with Psychotic Delirium.},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
volume = {},
number = {},
pages = {1-3},
doi = {10.1017/cjn.2026.10589},
pmid = {41969246},
issn = {0317-1671},
}

@article {pmid41969370,
year = {2026},
author = {Jun, S and Wang, XH and Zhou, L and Ozsahin, I and Maloney, T and Spector, E and Hojjati, SH and Tanzi, E and Razlighi, QR and Li, Y and Chiang, GC and de Leon, MJ and Rusinek, H and Glodzik, L and Butler, T},
title = {Cross-sectional investigation of choroid plexus calcification, cardiovascular risk score, and APOEε4 Status in cognitively normal cohort.},
journal = {Cerebral circulation - cognition and behavior},
volume = {10},
number = {},
pages = {100537},
pmid = {41969370},
issn = {2666-2450},
abstract = {The choroid plexus (CP), known for producing cerebrospinal fluid, is increasingly implicated in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies document structural CP alterations in aging and AD. One such alteration, calcium deposition, increases with age and is typically considered benign, though the mechanism and clinical significance of CP calcification remain uncertain. Given established association between peripheral vascular calcification and cardiovascular risk, we hypothesized that the volume of calcium within CP would correlate with systemic cardiovascular health. Based on prior findings of APOEε4-specific associations between CP calcium and neurodegeneration, participants were stratified by APOEε4 status, a strong genetic risk factor for AD also implicated in cardiovascular disease. In this retrospective analysis of 105 adults (mean age 58.9 years; 39 APOEε4+), we examined whether CP calcium correlates with cardiovascular risk in cognitively normal adults. CP calcium was quantified using a previously validated MRI-CT method. Spearman correlations assessed the association of CP calcium and Framingham Cardiovascular Risk Score (FCRS), as well as individual cardiovascular risk factors. Overall, CP calcium was not associated with FCRS. Among APOEε4- subjects, CP calcium correlated positively with FCRS (ρ = 0.26, p = 0.03). Conversely, APOEε4+ subjects showed an unexpected inverse correlation between CP calcium and systolic blood pressure (ρ = -0.38, p = 0.02). Greater CP calcium in association with higher FCRS in APOEε4- individuals mirrors the established link between CAC and cardiovascular risk, suggesting potential for CP calcium as an intracranial marker of vascular health. Divergent findings in APOEε4+ carriers may reflect CP-specific pathways relevant to APOEε4-driven AD pathogenesis.},
}

@article {pmid41969962,
year = {2026},
author = {İlhan, N and Keskin, E and Şahin, E and Alaylıoğlu, M and Samancı, B and Çamoğlu, T and Yurttaş, Z and Sordu, P and Ildız, S and Ayaz, G and Yediel, BŞ and Azzouz, SS and Bilgiç, B and Hanağası, HA and Gürvit, İH and Ak, DG and Dursun, E},
title = {The mRNA Expression Levels of General Transcription Factors Altered in Alzheimer Cases Possibly Due to Amyloid Beta 1-42 Exposure.},
journal = {Noro psikiyatri arsivi},
volume = {63},
number = {},
pages = {341-349},
pmid = {41969962},
issn = {1300-0667},
abstract = {INTRODUCTION: Given the global gene expression alterations associated with amyloid beta (Aβ), a hallmark of Alzheimer's disease (AD) pathology, this study aimed to investigate its potential role in modulating gene expression through the regulation of specific transcription factors (TFs).

METHODS: Using a combination of protein-protein interaction prediction tools and transcriptional regulatory interaction databases, we identified JUN, FOS, ATF2, ATF4, RELA, NF-κB, SMAD3, STAT1, STAT3, and SP1 as potential candidate TFs that might be involved in Aβ1-42 related pathways. We then conducted in vitro studies to demonstrate a direct effect of Aβ on these TFs and a case-control study to investigate any alterations of selected TFs in human samples. In vitro studies included HEK293 T cells treated with 0.09 µM and 10 µM Aβ1-42. The expression levels of the TFs were assessed by qRT-PCR. The mRNA expression levels of selected target transcription factors that have the highest PPI scores, namely JUN, FOS, and RELA, were also investigated in blood samples from core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker-confirmed AD cases and plasma ALZpath pTau217-confirmed healthy subjects.

RESULTS: In vitro studies indicated that the mRNA expression of most of the TFs was altered due to either the dose of Aβ or the period of treatments. JUN, FOS, NFKB, and SP1 mRNA expression were increased, while STAT1 and ATF2 were decreased within 24 hours of at least one dose of Aβ treatment. At 48 hours of treatment, FOS, STAT1, STAT3, ATF2, and SP1 were higher, whereas RELA, SMAD3, and NFKB were lower in Aβ-treated groups. At 72h of treatments, the ATF4 and NFKB expressions were high, whereas JUN FOS, RELA, STAT1, STAT3, ATF2, and SP1 were low in Aβ treated groups. Human samples showed that the mRNA levels of JUN and RELA were significantly higher in blood samples from AD cases compared to those from healthy individuals.

CONCLUSION: Alterations in the expression levels of TFs in response to Aβ exposure may explain the alterations of the expression levels of genes that these TFs regulate. Given that, understanding the transcriptional effects of Aβ and its regulatory role on TFs may provide a perspective for the physiological roles of Aβ and the molecular pathways underlying AD pathogenesis.},
}

@article {pmid41970019,
year = {2026},
author = {S, SV and P, J},
title = {Alzheimer's disease detection using a quantum deep neural network with Haralick feature extraction and simulated annealing optimization.},
journal = {PeerJ. Computer science},
volume = {12},
number = {},
pages = {e3387},
pmid = {41970019},
issn = {2376-5992},
abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder that affects a wide range of individuals worldwide. It is of utmost importance to detect AD at an earlier stage and diagnose it to manage the disease effectively. Detecting AD using traditional methodologies is not cost-effective and time-consuming because of the clinical tests and neuroimaging methods involved. Over the last few years, quantum computing and deep learning (DL) have become practical approaches for detecting and diagnosing AD. Unlike conventional methods, quantum computing allows for faster solving complex and entangled computable problems. DL models have a high potential for automatically learning and extracting pertinent features even from larger datasets. Hence, a new approach combining multiple concepts such as deep neural network (DNN), quantum computing, simulated annealing (SA) optimisation, and Haralick feature extraction has been proposed in this work for detecting AD. A quantum deep neural network (QDNN) is introduced in this article to take over the extraordinary computational capability of quantum systems. Haralick feature extraction is implemented in this study to extract the texture features from the medical images, resulting in a rich feature set for the model. The dataset used in this study, The Best Alzheimer's MRI Dataset contains 11,519 axial MRI images in .jpg format with a resolution of 128 × 128 pixels, categorised into four balanced classes-no impairment, very mild impairment, mild impairment, and moderate impairment-each comprising 2,560 images. To optimise the Haralick features from medical images and to enhance the model's learning process with optimised parameters, a new feature-specific simulated annealing method (FSSA) has been introduced in this article. The experimental results proved that our model achieved an accuracy of 98%, a precision of 99%, a sensitivity of 97%, and a specificity of 98%. The results achieved in this study are better than the traditional model's performance, and thus better in all performance metrics. The results indicated that the proposed QDNN model is a good framework for AD detection.},
}

@article {pmid41970054,
year = {2026},
author = {Eslami-Amirabadi, M and Scheffler, A and Kramer, JH and Gorno-Tempini, ML and Seeley, WW and Rosen, H and Rabinovici, GD and Miller, BL and Chiong, W and Rankin, KP},
title = {Additive effect of patient anosognosia and theory of mind deficit on dementia caregiver distress.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1724172},
pmid = {41970054},
issn = {1664-2295},
abstract = {INTRODUCTION: Caregiver distress in dementia is multifactorial. The contribution of disease specific factors including anosognosia (poor awareness of cognitive/behavioral deficits) and theory of mind (ToM) deficit (difficulty with understanding other's perspective) requires further investigation.

METHOD: Cross sectional secondary analysis was performed on a dataset of 205 research participants (age = 64.2 ± 9.46): 57 Alzheimer's disease, 38 behavioral variant frontotemporal dementia, 12 non-fluent primary progressive aphasia (PPA), 24 semantic variant PPA, 18 progressive supranuclear palsy syndrome, 14 corticobasal syndrome, and 42 cognitively normal controls (NC). Anosognosia was measured using the Patient Competency Rating Scale (PCRS-self minus PCRS-caregiver; clinically meaningful anosognosia >20 points difference), ToM deficit was evaluated using The Awareness of Social Inference Test: Social Inference-Enriched (TASIT-SIE), and caregiver distress was measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q) Total Distress score. Differences across syndromes were evaluated controlling for age and sex, and multivariable linear regression was used to determine predictors of caregiver distress.

RESULTS: Clinically meaningful anosognosia (patient overestimation of function) and ToM deficit were significantly higher in all dementia syndromes compared to NCs. Anosognosia and ToM deficit each independently predicted caregiver distress and had an additive effect (p < 0.05).

DISCUSSION: Our findings are consistent with other research showing that anosognosia in individuals with chronic neurological disorders including dementia can increase caregiver distress; however, our results highlight the additive importance of patients' theory of mind deficits above and beyond their anosognosia. Evaluation of both patient anosognosia and ToM deficit in clinical contexts may provide meaningful information to predict which caregivers are at particular risk for adverse outcomes.},
}

@article {pmid41970152,
year = {2026},
author = {Lourdel, C and Launay, A and Couteau, A and Bomia, D and Pointereau, S and Bulteau, S and Tessier, F and Thevenet, S and Ahoure, C and Belloeil, V and Robert, G and Taudin, N and Manivel, L and Daucé-Fleuret, L and Richomme, C and Camus, V and Brit, S and Léger, J and Desmidt, T},
title = {The I-Learn Cognition and Behavior program for non-pharmacological treatment of agitation in nursing home residents with neurocognitive disorders: A cluster randomized trial.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {2},
pages = {e70232},
pmid = {41970152},
issn = {2352-8737},
abstract = {INTRODUCTION: The "I-Learn Cognition and Behavior" program, integrating e-learning and simulation, aims to equip long-term care facility staff with non-pharmacological approaches for managing agitation in residents with neurocognitive disorders. This study evaluated the program's effectiveness.

METHOD: In this multicenter cluster-randomized trial, long-term care facilities served as the randomization units for a population of residents with neurocognitive disorders and agitation who underwent blinded assessments at baseline, 3, 6, and 10 months. Assessments included the Cohen-Mansfield Agitation Inventory (CMAI) as the primary outcome, the Neuropsychiatric Inventory-Nursing Home (NPI-NH), the Quality of Life in Alzheimer's Disease questionnaire, the Maslach Burnout Inventory (MBI), psychotropic use, and hospitalizations. Mixed-effects models analyzed changes in outcomes.

RESULTS: Twelve long-term care facilities were randomized to receive the I-Learn program (intervention) or usual care (control). One hundred sixty-nine residents were enrolled. There were no significant differences in total CMAI score changes between groups. The intervention group demonstrated significant reduced CMAI non-aggressive verbal agitation, MBI depersonalization, and psychotropic medication use (higher withdrawal rates and lower dosage increases) compared to the control group. NPI-NH scores decreased less in the intervention group.

DISCUSSION: The I-Learn program demonstrated potential for improving specific aspects of agitation in residents and well-being in caregivers while significantly reducing psychotropic medication use. "I-Learn Cognition and Behavior" is an easily accessible program with the potential for widespread distribution, contributing to improved well-being and quality of care in long-term care facilities for managing agitation in residents with neurocognitive disorders.},
}

@article {pmid41970254,
year = {2026},
author = {Yu, Y and Yu, JJ and Ding, SW and Zhang, G and Liu, Y and Guo, RB and Zang, J and Zhao, XX and Li, XT and Kong, L},
title = {An engineered ROS-responsive cascade nanoplatform delays Alzheimer's disease progression via Nrf2/GPX4-mediated microglial functional reprogramming.},
journal = {Materials today. Bio},
volume = {38},
number = {},
pages = {103055},
pmid = {41970254},
issn = {2590-0064},
abstract = {Alzheimer's disease (AD) is driven by a self-amplifying pathological network in which microglia-mediated neuroinflammation, oxidative stress, and cerebral iron dyshomeostasis are tightly interconnected. Here, we report a ROS-responsive, cascade-targeted nanoplatform (KMAI@NPs) engineered to intervene at this microglia-centered regulatory hub. The nanoplatform integrates an acetylsalicylic acid-modified dextran self-assembly core with PEGylated peptide modules for cascade targeting. By systematically optimizing the dextran molecular weight and acetylsalicylic acid grafting ratio, the self-assembly behavior and in vivo stability of the nanoplatform were rationally tuned. KMAI@NPs efficiently penetrate the blood-brain barrier, exhibit prolonged circulation, and selectively target activated microglia. Mechanistically, KMAI@NPs regulate microglial polarization and inhibit ferroptosis. In particular, given that M2-polarized microglia are more susceptible to ferroptosis, KMAI@NPs further protect these beneficial cells from ferroptotic injury through activation of the Nrf2/GPX4 axis, thereby preserving their anti-inflammatory and neuroprotective functions under inflammatory and iron-overload conditions. In APP/PS1 transgenic mice, KMAI@NPs markedly alleviate neuroinflammation, iron overload, amyloid pathology, and neuronal ultrastructural damage, resulting in significant cognitive improvement. This work establishes a microglia-centered, multitarget nanotherapeutic strategy that enables coordinated regulation of neuroinflammation, oxidative stress, and iron dyshomeostasis in AD.},
}

@article {pmid41970470,
year = {2026},
author = {Yang, C},
title = {Designing implicit population learners: a permutation-equivariant state space approach for brain disease diagnosis.},
journal = {Frontiers in computational neuroscience},
volume = {20},
number = {},
pages = {1780552},
pmid = {41970470},
issn = {1662-5188},
abstract = {INTRODUCTION: Group-aware learning has recently emerged as a promising paradigm for neuroimaging-based disease diagnosis, as population-level interactions can provide complementary information beyond individual imaging features. However, most existing approaches rely on explicitly constructed graphs, which introduce non-trivial design choices, scalability limitations, and sensitivity to graph topology. By incorporating the design philosophy of participatory interaction, we propose IP-Mamba, a scalable and memory-efficient framework tailored for neuroimaging cohorts that models implicit population interactions without the computational burden of explicit graph construction.

METHODS: IP-Mamba treats a mini-batch of subjects as an unordered set and employs a bidirectional Mamba-based sequence modeling mechanism to capture latent inter-subject dependencies. To address the inherent order sensitivity of sequence models, we introduce a Shuffle Consistency Strategy, which promotes permutation equivariance under random permutations of subject order, thereby aligning the model behavior with the clinically-relevant, set-based nature of population data. This design enables efficient implicit hypergraph modeling while maintaining linear computational complexity with respect to the population size. We evaluate IP-Mamba on the OASIS-1 dataset, focusing on the binary classification of Alzheimer's disease (Normal Controls vs. Abnormal) as an early clinical screening task. To address severe class imbalance and ensure diagnostic stability, we implement a Contextual Population Support Set inference mechanism coupled with a robust hybrid SVM decision layer.

RESULTS: Experimental results demonstrate that IP-Mamba achieves a balanced accuracy of 87.84% and maintains a high sensitivity (Recall) of 89% for the minority disease class. Compared to conventional 3D CNNs and Transformer-based baselines, IP-Mamba provides highly competitive diagnostic robustness while maintaining a highly efficient linear O(N) memory scaling without the quadratic computational bottlenecks typical of graph-based attention networks.

DISCUSSION: Comprehensive ablation studies further confirm the necessity of bidirectional modeling and shuffle consistency regularization. Overall, IP-Mamba offers a principled, memory-efficient alternative to explicit graph-based methods, providing a scalable solution for population-aware neuroimaging analysis under imbalanced clinical settings.},
}

@article {pmid41970526,
year = {2026},
author = {Fong, JC and Chavez, FI and Silos, K and Arroyo-Miranda, ML and Castro, GC and Kunik, ME and Shulman, JM and Medina, LD},
title = {The words community dwelling, Spanish-preferring Mexican/Mexican American adults use to talk about Alzheimer's disease and genetic testing: Implications for education and outreach.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {},
pages = {e70241},
pmid = {41970526},
issn = {2352-8737},
abstract = {INTRODUCTION: Hispanic/Latino (H/L) adults are more likely than non-Hispanic White individuals to have Alzheimer's disease (AD), yet fewer than one in five H/L adults has apolipoprotein E (APOE) Ɛ4, underscoring gaps in understanding genetic risk across H/L heritage groups. H/L adults remain underrepresented in AD research that uses genetic data for participant stratification. To inform culturally appropriate educational materials for 16 million U.S. Spanish speakers, we identified culturally salient words Spanish-preferring H/L adults use to describe AD and genetic testing beyond APOE.

METHODS: Community-residing, Spanish-preferring Mexican/Mexican American adults (n = 14) completed freelisting interviews, a method eliciting group-level concepts by identifying culturally salient words. Participant responses were analyzed using inductive thematic analysis and frequency calculations.

RESULTS: Participants recognized AD as a memory disorder influenced by aging and genes but were largely unfamiliar with AD genetic testing. Testing was viewed as useful for diagnosis rather than future risk prediction, with limited perceived value for cognitively normal individuals without a family history. Despite this limited familiarity, participants expressed interest in AD research involving genetic testing.

DISCUSSION: Findings suggested a perceived responsibility to use AD genetic testing despite limited awareness of its purposes, applications, and clinical implications. Participants' responses reflected a present-oriented health disposition: Genetic testing was viewed as appropriate once symptoms emerge rather than as a proactive tool for anticipating future decline, consistent with current clinical practice outside autosomal dominant AD. Educational materials co-created by community members and researchers may address these gaps by explaining both limitations of genetic testing in isolation and its potential future applications, including how genetic and multimodal biomarker data may inform risk estimation and prevention-focused decision-making. This approach may foster a future-oriented health disposition while remaining responsive to social and structural contexts. Future work is needed among other H/L heritage groups with differing social and structural experiences, migration histories, and language primacy.},
}

@article {pmid41970528,
year = {2026},
author = {Zlatar, ZZ and Gigliotti, C and Arias, I and Aceves, RG and Perez, M and Little, EA and Evans, C and Soria, JA and Huisa, BN and Jacobs, DM and Galasko, D and Salmon, DP and Peavy, GM},
title = {Promotores program to increase Hispanic/Latino(a) participation in Alzheimer's disease research.},
journal = {Alzheimer's & dementia (New York, N. Y.)},
volume = {12},
number = {},
pages = {e70249},
pmid = {41970528},
issn = {2352-8737},
abstract = {INTRODUCTION: Hispanic/Latino(a/x) (H/L) representation in Alzheimer's disease and related dementias (ADRD) research remains low, limiting generalizability of findings and interventions to this growing population. H/L community health workers ("Promotores") can enhance awareness of brain health and help guide their communities toward ADRD research opportunities; however, the effectiveness of recruitment through Promotores compared to traditional clinic-based approaches remains unknown. This study evaluates our Promotores training and compares the two approaches on recruitment success and characteristics of those recruited into a longitudinal study of ADRD.

METHODS: Nine Promotores completed Building Research Integrity and Capacity (BRIC) training on research concepts and ethics, and video training modules on ADRD-related research procedures. Training effectiveness was evaluated via pre-/post-tests to evaluate content knowledge and program satisfaction was evaluated by a self-report survey. Recruitment success was compared between Promotores-based and clinic-based approaches, assessing numbers referred and enrolled in ADRD research, and participants' demographic and clinical characteristics and agreement to specific research procedures (i.e., lumbar puncture, brain donation).

RESULTS: Promotores showed significant gains in knowledge of research concepts (Wilcoxon test, p = 0.005; median increase = 52%, 95% confidence interval [CI] = 30%-70%) and ADRD content (p = 0.042; median increase = 10%, 95% CI = 5%-40%). Promotores strongly agreed (on a 5-point Likert scale) that their training improved understanding of researcher responsibilities (x̄ = 4.88 ± 0.35), participant rights (x̄ = 4.25 ± 1.49), and ADRD research procedures (x̄ = 3.88 ± 1.36). Satisfaction with training materials (x̄ = 4.63 ± 0.74) and perceived community benefit (x̄ = 4.75 ± 0.46) were high. Promotores and clinic pathways had similar enrollment proportions (12.6% vs. 16.5%; Χ [2] = 0.92, p = 0.34) and participants were comparable across demographic, clinical, social determinants of health, and willingness to undergo research procedures.

DISCUSSION: The Promotores training program was well received, improved research literacy, and was as successful as clinic-based recruitment in enrolling older H/L adults into ADRD research. Results validate our Promotores training strategy and support a multipronged community-oriented approach to H/L participation in ADRD research.},
}

@article {pmid41970809,
year = {2026},
author = {Kherachi, R and Daoud, I and Melkem, N and Chelihi, A and Al-Shuhaib, MBS and Hamouda, S and Meawad, SB and El-Arabey, AA and Abdalla, M},
title = {In silico investigation of 4-(Trifluoromethyl)benzohydrazide derivatives as potential anti-Alzheimer's agents by targeting acetylcholinesterase and butyrylcholinesterase.},
journal = {In silico pharmacology},
volume = {14},
number = {1},
pages = {111},
pmid = {41970809},
issn = {2193-9616},
abstract = {UNLABELLED: Alzheimer's disease (AD) is a condition that mostly affects individuals in the latter stages of life. Due to the importance of inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in improving cholinergic transmission in the brain, both enzymes were targeted to provide a direct therapeutic approach against AD. In this study, we examined a novel set of derivatives of 4-(Trifluoromethyl)benzohydrazide, which have been identified for their potential to prevent the progression of the aforementioned illness. In this study, various computational techniques, including molecular docking, molecular dynamics (MD) simulations, bioisosteric replacement, and ADMET predictions, were utilized to discover potential inhibitors of AChE and BuChE from a set of twenty-five compound derivatives. The most promising inhibitors for each target, namely 2 s for AChE (- 7.674 kcal/mol) and 2r for BuChE (- 6.144 kcal/mol), along with their isosteres, were identified based on their high docking scores. Furthermore, the stability of these inhibitors was confirmed through MD simulation, and they exhibited favorable drug-likeness properties and safety profiles. Hence, it is essential to do more research to advance their potential as pharmaceutical agents for the treatment of AD.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00605-8.},
}

@article {pmid41970971,
year = {2026},
author = {Li, L and He, H and Wang, Y},
title = {Insulin and IGF signaling in the brain: multilevel regulation of synaptic and network homeostasis.},
journal = {Frontiers in endocrinology},
volume = {17},
number = {},
pages = {1793536},
pmid = {41970971},
issn = {1664-2392},
mesh = {Humans ; *Homeostasis/physiology ; *Signal Transduction/physiology ; *Brain/metabolism ; Animals ; *Insulin/metabolism ; Neuronal Plasticity/physiology ; *Synapses/metabolism ; *Somatomedins/metabolism ; *Nerve Net/metabolism ; },
abstract = {Insulin and insulin-like growth factor (IGF) signaling function as central regulators of synaptic homeostasis, bridging cellular metabolism with plasticity across molecular, synaptic, and network levels. Insulin signaling, is characterized as rapid and transient, and regulates energy metabolism, receptor trafficking, and short-term plasticity, whereas IGF signaling, with more sustained activity, supports neuronal survival, dendritic growth, and long-term remodeling. Together, they contribute to synaptic homeostasis through AMPAR/NMDAR modulation, astrocytic coupling, and activity-dependent scaling. Disruption of these regulatory processes has been associated with aberrant plasticity and altered network stability in Alzheimer's disease, epilepsy, and diabetic encephalopathy, highlighting their pathophysiological significance. This review synthesizes recent evidence to propose an integrative framework in which insulin and IGF signaling acts as a molecular hub linking metabolic state to synaptic homeostasis. Understanding this cross-scale regulation not only clarifies how metabolic disturbances lead to cognitive decline but also establishes a foundation for novel therapeutic strategies aimed at restoring neural network function in metabolic and neurodegenerative disorders.},
}

Humans
*Homeostasis/physiology
*Signal Transduction/physiology
*Brain/metabolism
Animals
*Insulin/metabolism
Neuronal Plasticity/physiology
*Synapses/metabolism
*Somatomedins/metabolism
*Nerve Net/metabolism

@article {pmid41971015,
year = {2026},
author = {Cai, Y and Han, S and Zhao, M and Xiang, X and Zhang, Y and Zhang, L and Lai, Q and Wang, J and Liao, L},
title = {Prevotella intermedia oral infection induces cognitive impairment in C57BL/6 mice via neuroinflammation and barrier damage.},
journal = {Journal of oral microbiology},
volume = {18},
number = {1},
pages = {2652170},
pmid = {41971015},
issn = {2000-2297},
abstract = {BACKGROUND: Oral pathogens play a significant role in the pathogenesis of Alzheimer's disease (AD) via the oral-brain axis and oral-gut-brain axis. However, how Prevotella intermedia (P. intermedia) affect the development of AD remains unclear.

OBJECTIVE: To investigate the effects of P. intermedia infection on neuroinflammation and cognitive function.

DESIGN: Sixty C57BL/6 mice were divided into two cohorts and infected with P. intermedia via gingival injection or oral gavage, mimicking pathogen invasion. The microbiota changes of saliva collected from 5 AD patients and 5 healthy individuals were analyzed by 16S rRNA sequencing.

RESULTS: Gingival injection resulted in cognitive impairment, neuronal loss in the hippocampal CA1/CA3 regions (p < 0.05), overactivation of microglia and increased expression of proinflammatory cytokines (IL-1β and TNF-α, p < 0.05) and NF-κB in hippocampus (p < 0.05). Similar cognitive impairments and cerebral changes were noted after oral gavaging. Additionally, oral gavage induced gut microbiota dysbiosis, intestinal inflammation and decreased expression of tight junction in intestinal barrier and blood-brain barrier (ZO-1, Occludin, Claudin-1 and Claudin-5, p < 0.05). Furthermore, AD patients exhibited oral microbiota dysbiosis, with a higher relative abundance of P. intermedia (p < 0.05).

CONCLUSION: P. intermedia is associated with cognitive impairment and AD-related neuroinflammation via the oral-brain and oral-gut-brain axes.},
}

@article {pmid41971324,
year = {2026},
author = {Wang, B and Deng, F and Liu, Z and Tian, J and Li, Y and Mao, Y and Song, H},
title = {Clinical application of fecal microbiota transplantation and its influencing factors.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1807071},
pmid = {41971324},
issn = {1664-302X},
abstract = {Fecal microbiota transplantation (FMT) is an emerging therapy that has received significant attention in recent years, although its origins can be traced back to 4th-century China. In modern medicine, FMT has been incorporated into clinical guidelines for the treatment of recurrent Clostridioides difficile infection. By re-establishing a healthy gut microbiota and regulating the immune system, FMT has potential therapeutic effects on various diseases, such as gastrointestinal diseases, diabetes, tumors, Alzheimer's disease, and liver disease. However, its efficacy varies based on the type of disease and individual differences. The clinical application of FMT is influenced by multiple factors, including fecal matter processing, administration route, dosage, donor screening, and recipient detection. Currently, FMT faces numerous challenges, including the need to verify the stability and durability of its efficacy, standardize donor screening criteria, and optimize fecal processing and administration. Future research is expected to reveal the mechanisms of action of FMT, optimize treatment protocols, and refine its safety, efficacy, and convenience, thereby bringing hope for patients with complex and challenging diseases.},
}

@article {pmid41971333,
year = {2026},
author = {Shen, H and Wang, SY and Zhao, YY and Zhou, JL and Zhao, J and Zhu, WK},
title = {Brain-gut-microbiota axis: a review on the bidirectional regulatory mechanisms between gut microbiota and brain and their disease interactions.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1768891},
pmid = {41971333},
issn = {1664-302X},
abstract = {OBJECTIVE: To synthesize current evidence on the bidirectional regulatory mechanisms of the Brain-Gut-Microbiota Axis (BGMA), its perturbation by external factors, and its clinical implications for neurodegenerative, psychiatric, metabolic, and gastrointestinal disorders.

DESIGN: Narrative review integrating preclinical and clinical evidence.

DATA SOURCES: PubMed/Medline, EMBASE, Cochrane Library searches (2000-2023) using keywords: "brain-gut-axis," "microbiota," "dysbiosis," "neuroinflammation," "SCFAs," "neurodegeneration," "psychobiotics."

RESULTS: Diet, stress, antibiotics, and environment significantly alter gut microbiota composition (e.g., reducing diversity, shifting Firmicutes/Bacteroidetes (F/B) ratio). Dysbiosis disrupts BGMA communication via: (1) Neural pathways (vagus nerve modulation); (2) Immune activation (cytokine release, neuroinflammation); (3) Microbial metabolites (SCFAs, tryptophan derivatives, TMAO). These disruptions are associated with Alzheimer's disease (reduced Faecalibacterium, amyloid deposition), Parkinson's (elevated TMAO, α-synuclein aggregation), and depression (altered serotonin synthesis), though causality remains to be established in human studies.

CONCLUSION: The BGMA is a critical mediator of systemic health. Dysbiosis contributes to disease pathogenesis through defined neural, immune, and metabolic pathways. Targeting the microbiota offers novel therapeutic strategies. Future research must prioritize translational studies validating microbial biomarkers and interventions in human cohorts.},
}

@article {pmid41971579,
year = {2026},
author = {Gu, S and Yin, W and Xie, M and He, C and Bian, Y and Li, L and Lu, W and Wang, Q},
title = {Isoquinoline alkaloids in Coptis chinensis to treat Alzheimer's disease through promoting growth of Bifidobacterium breve inhibiting abnormal autophagy using a novel AI high-content intelligent imaging system.},
journal = {Chinese herbal medicines},
volume = {18},
number = {2},
pages = {405-419},
pmid = {41971579},
issn = {2589-3610},
abstract = {OBJECTIVE: Coptis chinensis has been shown to increase beneficial intestinal bacteria and treat Alzheimer's disease (AD). Bifidobacterium breve can effectively treat AD through the gut-brain axis. Therefore, this study aimed to study the joint effects of C. chinensis and B. breve in the treatment of AD.

METHODS: 16S rRNA was used to test the abundance of bacterial flora in APPswe/PS1ΔE9 mice after C. chinensis administration. To determine the efficacy of C. chinensis combined with B. breve on AD, pathological section staining, Barnes maze, Western blotting and ELISA were utilized to confirm the improvement of cognitive dysfunction in AD mice after administration. In order to elucidate the pharmacodynamic components of monomers in C. chinensis, network pharmacology was used to screen the components related to autophagy and confirm the pharmacodynamic effects by artificial intelligence (AI) high-content intelligent imaging.

RESULTS: The results of 16S rRNA sequencing indicated that C. chinensis could modulate the abundance of B. breve in AD mice. Pathological assessments, Barnes maze testing, and additional experiments have shown that C. chinensis combined with B. breve can improve the memory and learning ability of AD mice by reducing neuronal apoptosis and amyloid-β (Aβ) peptide deposition. Network pharmacology combined with AI high-content intelligent imaging technology and Western blotting experiments demonstrated that magnoflorine, 13-methylberberine and palmatrubine in C. chinensis could exert neuroprotective effects in AD mice by up-regulating p62 protein expression while down-regulating Beclin-1 and microtubule-associated protein 1 light chain 3 II (LC3II) protein levels, thereby modulating autophagy-related pathways.

CONCLUSION: C. chinensis can enhance the abundance of beneficial bacteria in the gut and ameliorate cognitive dysfunction in AD mice by interacting with B. breve. Moreover, magnoflorine, 13-methylberberine, and palmatrubine within C. chinensis can also mitigate excessive autophagy and oxidative stress in nerve cells.},
}

@article {pmid41971641,
year = {2026},
author = {Thomas, KR and Terao, CM and Weigand, AJ and Petersen, M and O'Bryant, S and Clark, AL and , },
title = {Subjective memory concerns and AD/ADRD plasma biomarker associations in HABS-HD.},
journal = {Alzheimer's & dementia (Amsterdam, Netherlands)},
volume = {18},
number = {},
pages = {e70324},
pmid = {41971641},
issn = {2352-8729},
abstract = {INTRODUCTION: We examined relationships among subjective memory concerns (SMC), plasma biomarkers, and objective memory within racially/ethnically diverse older adults.

METHODS: Participants included 1618 cognitively unimpaired older adults (681 Hispanic/Latino [H/L], 164 non-Hispanic Black [NHB], 773 non-Hispanic White [NHW]) from the Health and Aging Brain Study-Health Disparities. Associations among SMC, plasma biomarkers (phosphorylated tau 181 [p-tau181], amyloid beta 42/40 [Aβ42/40], neurofilament light chain [NfL], total tau [t-tau]), and objective memory were examined.

RESULTS: Higher SMC was associated with higher plasma p-tau181 and NfL levels in NHW participants only. Higher depressive symptoms were associated with higher plasma p-tau181 in NHB participants only. Higher SMC related to lower objective memory for H/L and NHW participants. Plasma biomarkers had unique patterns of association with memory tests by racial/ethnic group.

DISCUSSION: Different patterns of subjective memory, objective memory, and plasma biomarker associations within racial/ethnic groups suggests variability in the utility of SMC for early detection of Alzheimer's disease-related changes.},
}

@article {pmid41971952,
year = {2026},
author = {Lee, EH and Jo, T},
title = {DuAL-Net: A Dual-Network Approach for Alzheimer's Disease Risk Prediction Using APOE-Centered Regional Whole-Genome Sequencing Data.},
journal = {Computational and structural biotechnology journal},
volume = {35},
number = {1},
pages = {0010},
pmid = {41971952},
issn = {2001-0370},
abstract = {Alzheimer's disease prediction using genomic data remains challenging due to the high dimensionality of whole-genome sequencing data and the complex relationships between genetic variants. We developed DuAL-Net (Dual Approach Local-global Network), a hybrid framework that integrates local genomic window analysis with global annotation-based modeling to prioritize disease-associated single-nucleotide polymorphisms (SNPs). As a proof of concept, we applied DuAL-Net to 14,094 SNPs within the APOE ±50-kb region from 1,050 individuals in the Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Sequencing Project (ADSP) cohorts. Using nested 5-fold cross-validation, DuAL-Net achieved an area under the receiver operating characteristic curve (AUC) of 0.698 (95% confidence interval: 0.659 to 0.737) for the top 100 ranked SNPs, substantially outperforming bottom-ranked SNPs (AUC = 0.479). Validation on an independent ADSP Alzheimer's Disease Centers cohort (n = 5,570) confirmed generalizability, with top-ranked SNPs achieving AUC = 0.686 versus 0.516 for bottom-ranked SNPs. The framework successfully identified established risk variants, including rs429358 and rs7412, validating its ability to prioritize biologically relevant SNPs. DuAL-Net provides a generalizable approach for integrating local and global genomic information in Alzheimer's disease risk prediction.},
}

@article {pmid41972106,
year = {2026},
author = {Du, Y and Li, S and Diao, J and Du, B and Jiang, G},
title = {Structural and functional brain alterations in depression with Alzheimer's disease and mild cognitive impairment: a multimodal coordinate-based meta-analysis.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1784966},
pmid = {41972106},
issn = {1663-4365},
abstract = {BACKGROUND: Depression is a common neuropsychiatric symptom in Alzheimer's Disease (AD) and mild cognitive impairment (MCI). Inconsistent results for comparison between AD with depression (ADD), MCI with depression (MCID), and those without depression were obtained from previous neuroimaging studies. Therefore, a multimodal coordinate-based meta-analysis was conducted in this study.

METHODS: We searched PubMed, Embase, PsycINFO and the Cochrane Library for neuroimaging studies on ADD and MCID patients from December 1995 to December 2025. Activation likelihood estimate (ALE) coordinate-based meta-analyses were performed to explore brain regions showing abnormalities in ADD and MCID compared to AD without depression (ADND) and MCI without depression (MCIND). Moreover, we performed modality and subgroup analysis of the difference in structural and neural activity.

RESULTS: A total of 30 studies, comprising 1973 participants (520 ADD patients, 297 MCID patients, 748 ADND patients, and 408 MCIND patients), were included in this meta-analysis. ADD and MCID showed significantly decreased gray matter volume (GMV) in the right hippocampus and neural activity in the right superior frontal gyrus (SFG) and left inferior temporal gyrus (ITG) compared to ADND and MCID. Subgroup analysis revealed decreased neural activity in the left SFG in the ADD group compared to the ADND group, and decreased neural activity in the right SFG and left ITG in the MCID group compared to the MCIND group.

CONCLUSION: Our findings that decreased GMV of the hippocampus and abnormal neural activities of SFG and ITG in ADD and MCID expand novel insights into the neural mechanisms of depression in AD and MCI, representing potential neural correlates for depression in ADD and MCID.},
}

@article {pmid41972107,
year = {2026},
author = {Nobukawa, S and Ikeda, T and Kikuchi, M and Takahashi, T},
title = {Age-group differences between young and middle-aged adults in spatiotemporal EEG dynamics revealed by instantaneous frequency microstate analysis.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1707228},
pmid = {41972107},
issn = {1663-4365},
abstract = {INTRODUCTION: The human brain exhibits complex functions that emerge from interactions among spatially distributed neural regions. Electroencephalography (EEG) microstate analysis has been widely adopted to capture transient topographies reflecting large-scale network dynamics; moreover, it has been linked to cognitive functions, intrinsic brain networks, and neuropsychiatric disorders. Building on this framework, we recently proposed a novel approach based on instantaneous frequency (IF), defined as the temporal derivative of the instantaneous phase, which characterizes microstates in a dimension distinct from that of conventional amplitude-based microstates by explicitly capturing the phase leading and lagging. Although IF microstates have shown promise in characterizing the pathology and cognitive decline in Alzheimer's, their relevance to normal aging has not been investigated. This study aimed to identify age-group differences in large-scale EEG-dynamic properties using IF microstates.

METHODS: We recorded resting-state EEG with eyes closed from 29 younger and 18 middle-aged healthy adults. IF time series were extracted from sensor-level EEG signals in the theta and alpha bands. The IF microstates were identified using a hidden Markov model to ensure temporal continuity in state segmentation. Subsequently, we evaluated the sensor-level spatial distributions, mean dwell times, occupancy, and transition probabilities of the IF microstates and assessed age-group differences using appropriate statistical tests with false discovery rate correction.

RESULTS: We identified several IF microstates characterized by frontal IF delay and occipital IF lead, as well as microstates deviating from these patterns. Group comparisons revealed age-group differences in dynamic properties; in the middle-aged group, mean dwell times increased in some states and decreased in others, while occupancy and transition probabilities also exhibited significant changes.

DISCUSSION: IF microstate analysis provides a novel and informative perspective on age-group differences in spatiotemporal EEG dynamics. This approach, which is distinct from conventional amplitude-based microstates, may be useful for understanding healthy aging neural mechanisms.},
}

@article {pmid41972397,
year = {2026},
author = {Schurman, CA and Kaur, G and Kaya, S and Bons, J and Aguirre, CG and Liu, Q and King, CD and Wilson, KA and Baker, HL and Hady, M and Luna, NM and Bieri, G and Villeda, SA and Ellerby, LM and Schilling, B and Alliston, T},
title = {Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e23511},
doi = {10.1002/advs.202523511},
pmid = {41972397},
issn = {2198-3844},
support = {/NH/NIH HHS/United States ; P30AR075055/AR/NIAMS NIH HHS/United States ; R01DE019284-14S1-Alzheimer's/DE/NIDCR NIH HHS/United States ; Disease Supplement: R01DE01928-11A1/DE/NIDCR NIH HHS/United States ; R01AG067740/AG/NIA NIH HHS/United States ; R01AG077770/AG/NIA NIH HHS/United States ; P01AG066591/AG/NIA NIH HHS/United States ; S10OD028654/AG/NIA NIH HHS/United States ; T32AG000266/AG/NIA NIH HHS/United States ; },
abstract = {Individuals with Alzheimer's disease (AD) are at an increased risk of bone fracture, while osteoporosis in women is one of the earliest predictors of AD. Yet the mechanisms linking cognitive decline and skeletal deterioration remain poorly defined. Proteomic analysis of cortical bone from aged 21-month-old mice revealed strong enrichment of neurodegeneration-associated proteins, including apolipoprotein E (Apoe) and amyloid precursor protein. Apoe localized specifically to osteocytes, with expression in aged female bone nearly twice that of young 4-month-old male bone. Because human APOE alleles confer different age-related AD risks, we examined their roles in bone using humanized APOE2, APOE3, and APOE4 knock-in mice and analyzed bone and hippocampus from the same animals. APOE4 produced marked sex-specific effects on the bone transcriptome and proteome compared with APOE2 or APOE3. Strikingly, APOE4-associated proteomic disruptions were stronger in female bone than in the hippocampus. Functionally, APOE4 caused bone fragility in females without altering cortical structure. These deficits stemmed from impaired osteocyte perilacunocanalicular remodeling. Our findings identify APOE4 as a molecular driver of early osteocyte dysfunction and reduced bone quality, disproportionately affecting females. These findings highlight osteocytes as potential targets for early diagnosis of age-related cognitive impairment and treatment for bone fragility, in females.},
}

@article {pmid41972598,
year = {2026},
author = {Travers-Lesage, V and Since, M and Wang, A and Davis, A and Fayolle, D and Bernay, B and Modeste, F and Nachon, F and Brazzalotto, X and Crouzier, L and Sopkova-De Oliveira Santos, J and Maurice, T and Dallemagne, P and Rochais, C},
title = {Rational Design and Evaluation of Rivastigmine-Based Pleiotropic Prodrugs for the Treatment of Alzheimer's Disease.},
journal = {ACS chemical neuroscience},
volume = {},
number = {},
pages = {},
doi = {10.1021/acschemneuro.6c00170},
pmid = {41972598},
issn = {1948-7193},
abstract = {The multifactorial origin of Alzheimer's disease (AD) is currently being addressed with the development of combination therapy or multitarget directed ligands. If the conventional approach of targeting acetylcholinesterase (AChE) for AD treatment has limitations, it could offer opportunities for a polypharmacological approach by designing covalent pseudoirreversible prodrugs inspired by rivastigmine's mechanism of action. This study focuses on introducing aminated drugs to the rivastigmine carbamate moiety, namely, fluoxetine and memantine, which have shown synergy with cholinesterase inhibition. These innovative carbamates target sustained drug release through covalent pseudoirreversible cholinesterase inhibition, strategically balancing inhibitory potency, selectivity, mechanism, and reactivation kinetics. This comprehensive approach demonstrates the potential of targeting ChE via a covalent mechanism and provides valuable insights into the structure-activity relationships of these derivatives. Interestingly, this study provides a useful biochemical toolbox for characterizing pseudoirreversible cholinesterase carbamate-type inhibitors. The most promising compound was evaluated in in cellulo and in vivo AD models, highlighting the potential of polypharmacological interventions as innovative and multifaceted anti-AD drugs.},
}

@article {pmid41972613,
year = {2026},
author = {Zhao, Y and Li, L and Tao, J and Yang, M and Li, C and Zhang, X and Zhang, Y and Sun, S and Zhao, N},
title = {Detection of Synaptic Vesicle Glycoprotein 2A in Serum Using a Polypyrrole-Functionalized Graphene Oxide Electrochemical Immunosensor.},
journal = {Nanomaterials (Basel, Switzerland)},
volume = {16},
number = {7},
pages = {},
doi = {10.3390/nano16070397},
pmid = {41972613},
issn = {2079-4991},
abstract = {Early intervention is pivotal for mitigating the progression of Alzheimer's disease (AD). This study presents an electrochemical immunosensor targeting synaptic vesicle glycoprotein 2A (SV2A) to facilitate early AD diagnosis. A sensing interface was engineered using a nanocomposite of graphene oxide (GO) and 3-carboxyl polypyrrole (3-COOH-PPy). Leveraging the synergistic effects between the large specific surface area of GO and the superior conductivity of 3-COOH-PPy, the composite established an efficient electron transport network. This architecture provided abundant active sites for capture antibody immobilization while significantly enhancing interfacial electron transfer kinetics. Coupling this interface with an enzyme-mediated signal amplification strategy based on the horseradish peroxidase (HRP)-catalyzed TMB/H2O2 system, the immunosensor achieved high sensitivity. It exhibited a wide linear range of 2 ng/mL to 16 μg/mL with a low limit of detection (LOD) of 0.15 ng/mL. Furthermore, successful detection in C57 mouse serum samples validated the method's reliability and potential for clinical application. In conclusion, this immunosensor offers a sensitive and robust platform for the early diagnosis of AD.},
}

@article {pmid41972681,
year = {2026},
author = {Thanos, JM and Campbell, OC and Natale, NR and Royo Marco, A and Puchalski, MA and Lukens, JR},
title = {The Genotoxic Stress Sensor ZBP1 Drives Tau Pathology.},
journal = {Cells},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/cells15070591},
pmid = {41972681},
issn = {2073-4409},
support = {R01AG071996/GF/NIH HHS/United States ; R01AG087406/GF/NIH HHS/United States ; RF1AG078684/GF/NIH HHS/United States ; R01AG086344/GF/NIH HHS/United States ; T32AI055432/GF/NIH HHS/United States ; F31NS135897/GF/NIH HHS/United States ; N/A//Owen's Family Foundation/ ; N/A//Cure Alzheimer's Fund/ ; N/A//The Harrison Family Foundation/ ; N/A//The Steven A Newman AD Award/ ; },
mesh = {Animals ; *DNA-Binding Proteins/metabolism/genetics ; *DNA Damage ; Mice ; *Tauopathies/pathology/metabolism/genetics ; *tau Proteins/metabolism ; Humans ; Astrocytes/metabolism/pathology ; Disease Models, Animal ; Microglia/metabolism/pathology ; Neurons/metabolism/pathology ; *RNA-Binding Proteins/metabolism ; Mice, Inbred C57BL ; },
abstract = {Genotoxic stress, which includes DNA damage and the mis-localization of DNA and RNA, is a defining feature of tauopathies, Alzheimer's disease, and several other neurodegenerative disorders. Recent findings indicate that activation of the innate immune system in response to genotoxic stress can drive harmful neuroinflammation, compromise neuronal integrity, and promote neurodegeneration. Multiple innate immune sensors of genotoxic stress have recently been discovered, but the contributions of many of these emerging nucleic acid-sensing pathways in neurodegenerative disease pathogenesis remain largely unexplored. Z-DNA binding protein 1 (ZBP1) is one such recently discovered genotoxic stress sensor that has been shown to incite various forms of cell death as well as proinflammatory cytokine production in response to left-handed Z conformations of DNA (Z-DNA) and RNA (Z-RNA). Here, we show that ZBP1 deletion provides protection against tau pathology and neuronal loss in the PS19 mouse model of tauopathy. Moreover, we find that this rescue of tauopathy seen with ZBP1 ablation is associated with dampened activation of microglia and astrocytes. These findings identify ZBP1 as a pivotal genotoxic stress sensor that drives tau pathology, gliosis, and neuronal loss in tauopathy. This work further suggests that targeting ZBP1 may offer a therapeutic strategy to treat tau-mediated neurodegenerative disease.},
}

Animals
*DNA-Binding Proteins/metabolism/genetics
*DNA Damage
Mice
*Tauopathies/pathology/metabolism/genetics
*tau Proteins/metabolism
Humans
Astrocytes/metabolism/pathology
Disease Models, Animal
Microglia/metabolism/pathology
Neurons/metabolism/pathology
*RNA-Binding Proteins/metabolism
Mice, Inbred C57BL

@article {pmid41972689,
year = {2026},
author = {Gaifullina, A and Belhi, C and Restivo, L and Chatton, JY},
title = {Astrocyte Mitochondrial UCP4 Reprograms Neuronal Network Oscillations via GDNF-Dependent K[+]-Ca[2+] Signaling in Alzheimer's Disease Mice.},
journal = {Cells},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/cells15070597},
pmid = {41972689},
issn = {2073-4409},
support = {2020-PI06//Synapsis Foundation Alzheimer Research Switzerland/ ; 310030-212432/SNSF_/Swiss National Science Foundation/Switzerland ; NA//University of Lausanne, Faculty of Biology and Medicine/ ; },
mesh = {Animals ; *Alzheimer Disease/metabolism/pathology ; *Astrocytes/metabolism ; *Glial Cell Line-Derived Neurotrophic Factor/metabolism ; Mice ; *Mitochondria/metabolism ; *Calcium Signaling ; *Neurons/metabolism ; Disease Models, Animal ; Mice, Transgenic ; Calcium/metabolism ; *Potassium/metabolism ; *Nerve Net/metabolism ; },
abstract = {Neuron-targeted therapies for Alzheimer's disease (AD) have shown limited efficacy, highlighting the need to explore glial-based mechanisms of neuroprotection. Here, we show that astrocyte mitochondrial uncoupling via viral overexpression of uncoupling protein 4 (UCP4) restores neuronal circuits and ion channel function in aged 3xTG AD mice with overt symptoms. Spontaneous local field potential recordings revealed a partial recovery of hippocampal and subicular sharp wave ripple oscillations, electrophysiological signatures of neuronal circuits known to be altered in AD. Combined whole-cell patch-clamp electrophysiology with two-photon Ca[2+] imaging further demonstrated that UCP4 modulates activity-dependent Ca[2+] influx, A-type potassium channel function, and enhances glial cell line-derived neurotrophic factor (GDNF) signaling. These findings identify astrocytic mitochondrial uncoupling as a potent mechanism enhancing neuronal resilience and restoring circuit function in symptomatic AD brains.},
}

Animals
*Alzheimer Disease/metabolism/pathology
*Astrocytes/metabolism
*Glial Cell Line-Derived Neurotrophic Factor/metabolism
Mice
*Mitochondria/metabolism
*Calcium Signaling
*Neurons/metabolism
Disease Models, Animal
Mice, Transgenic
Calcium/metabolism
*Potassium/metabolism
*Nerve Net/metabolism

@article {pmid41972916,
year = {2026},
author = {Li, Y and Wang, G and Xiong, C and Shan, G and Cao, Y and Llibre-Guerra, J and Hassenstab, J and McDade, E and Bateman, RJ},
title = {Statistical models for Alzheimer's disease clinical trials: Lessons learned from the DIAN-TU Platform Trial.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261441645},
doi = {10.1177/13872877261441645},
pmid = {41972916},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) clinical trials often involve uneven follow-up durations and long-term open-label extensions (OLE), yet conventional statistical models are typically designed for fixed schedules, limiting their efficiency in such settings.ObjectiveTo describe and illustrate alternative statistical modeling approaches developed and implemented in the Dominantly Inherited Alzheimer Network Trials Unit platform trial to optimally leverage data with irregular and extended follow-up.MethodsWe present three complementary models: (1) a Cox proportional hazards model for recurrent disease progression events that uses all observed worsening events rather than only the first event; (2) a parametric disease progression model based on estimated years from expected symptom onset that estimates proportional slowing or time delay in disease progression; and (3) piecewise linear mixed-effects models tailored to the "gap" period between the double-blind phase and OLE, accommodating variable off-treatment intervals and missing interim data. All methods are illustrated with hypothetical examples, and ready-to-use SAS code is provided in the Supplemental Material.ResultsThe proposed models successfully handle complex longitudinal data structures typical trials with OLE phases, offering greater statistical efficiency and more comprehensive capture of treatment effects over extended periods compared with traditional approaches.ConclusionsThese flexible, efficient statistical models are well-suited for rare disease and long-duration AD trials. Wider adoption and further validation of these approaches may enhance the power and interpretability of future neurodegenerative disease trials.},
}

@article {pmid41972921,
year = {2026},
author = {Harrington, EE and Bock, JE},
title = {Honor culture and cognitive aging: Honor endorsement and deficits in memory aging and Alzheimer's disease knowledge.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261441602},
doi = {10.1177/13872877261441602},
pmid = {41972921},
issn = {1875-8908},
abstract = {BackgroundIdentifying deficits in the public's memory aging knowledge is a promising avenue for improving our understanding of Alzheimer's disease (AD) risk and developing effective education and intervention strategies. Yet, it is important to contextualize knowledge within culturally relevant frameworks that may not only contribute to the extent of individuals' knowledge, but also to the reception of developed educational and intervention programs.ObjectiveOne prominent culture within the United States (U.S.) that has largely been neglected within AD research is the culture of honor, or those that prioritize the defense and maintenance of reputation.MethodsUsing an online sample, the present study examined 998 U.S. adults' endorsement of honor culture norms and knowledge of normal and pathological memory aging knowledge, as well as AD specific knowledge. Hierarchical linear regression analyses (controlling for age, sex, race/ethnicity, educational attainment, and dementia experience) examined associations between honor endorsement and each type of memory aging knowledge.ResultsGreater honor endorsement was associated with worse knowledge of normal memory aging, pathological memory aging, and AD. Exploratory analyses that examined links to domains of AD knowledge revealed that greater honor endorsement was specifically linked with worse knowledge related to AD risk factors, symptoms, treatment and management, life impact, and caregiving.ConclusionsThe present research advances our understanding of deficits in the public's memory aging knowledge within the context of U.S. honor cultures and highlights a need for the developmental of culturally relevant education and intervention efforts.},
}

@article {pmid41973103,
year = {2026},
author = {Kato, S and Hagiwara, A and Fujita, S and Uchida, W and Kamagata, K and Furuta, T and Akai, H and Abe, O and Motoi, Y and Hattori, N and Aoki, S},
title = {3D quantitative synthetic MRI for assessing Alzheimer's clinical syndrome, subjective cognitive impairment, and mild cognitive impairment.},
journal = {Neuroradiology},
volume = {},
number = {},
pages = {},
pmid = {41973103},
issn = {1432-1920},
support = {20K20185//Japan Society for the Promotion of Science/ ; 23K07189//Japan Society for the Promotion of Science/ ; 23K27556//Japan Society for the Promotion of Science/ ; JP24wm0625310//Japan Agency for Medical Research and Development/ ; JPMJFR231P//Fusion Oriented REsearch for disruptive Science and Technology/ ; JP19dm0307101//Japan Agency for Medical Research and Development, Japan/ ; },
abstract = {PURPOSE: For Alzheimer's Clinical Syndrome (ACS) and early cognitive decline (mild and subjective cognitive impairment, MCI/SCI), we used three-dimensional (3D) quantitative synthetic magnetic resonance imaging (MRI) with an interleaved Look-Locker acquisition sequence and a T2 preparation pulse (QALAS), which can acquire quantitative parameters in a single scan, to investigate the potential of quantitative parameters to add supplemental information to the structural imaging.

METHODS: Twenty-four ACS patients, 19 patients with MCI/SCI, and 24 age- and sex-matched healthy controls (HCs) underwent MRI. The differences in longitudinal relaxation time (qT1), transverse relaxation time (qT2), proton density (PD), myelin volume fraction (MVF), and gray matter volume among the groups were evaluated using voxel-based quantification (VBQ) and voxel-based morphometry (VBM). Logistic regression analyses were developed to distinguish between the ACS, MCI/SCI, and HC groups.

RESULTS: In the VBM and VBQ analyses, patients with ACS had significantly lower gray matter volume and MVF and higher qT1, qT2, and PD compared to the HC group. Compared to VBM, VBQ analysis identified broader areas of significance specifically in the insula and cerebellum vermis, known to atrophy as the disease progresses. Subtle differences in PD and MVF were observed between MCI/SCI and HC groups, and the AUC was significantly higher when the quantitative measures obtained with 3D-QALAS were combined than when logistic regression was performed with the brain volume alone (quantitative measures and volume: 0.79; volume: 0.58; p = 0.034).

CONCLUSIONS: 3D-QALAS integrates quantitative relaxometry and myelin-sensitive metrics reflecting water content and myelin integrity with structural information.},
}

@article {pmid41973126,
year = {2026},
author = {Shinde, P and Sathiyanarayanan, A and Lohidasan, S},
title = {Exploration of potential neuroprotective agents from medicinal plants for the treatment of Alzheimer's disease-approach through in silico ADMET, network pharmacology, docking, and dynamics studies.},
journal = {Journal of molecular modeling},
volume = {32},
number = {5},
pages = {},
pmid = {41973126},
issn = {0948-5023},
mesh = {*Alzheimer Disease/drug therapy ; *Molecular Docking Simulation ; *Neuroprotective Agents/chemistry/pharmacology/pharmacokinetics/therapeutic use ; Molecular Dynamics Simulation ; Network Pharmacology ; Humans ; *Plants, Medicinal/chemistry ; *Phytochemicals/chemistry/pharmacology/pharmacokinetics ; },
abstract = {CONTEXT: A degenerative brain disorder that causes memory loss is Alzheimer's disease (AD). Phytoconstituents represent a promising therapeutic strategy due to their diverse bioactivities and favourable safety profiles. This study aimed to identify potential neuroprotective phytoconstituents for AD by pharmacokinetic screening, network pharmacology, molecular docking and molecular dynamics simulation. Among 22 phytoconstituents analysed, the network revealed GSK3β, STAT3, MAOB, ESR1, and PTGS2 as key AD-associated targets. Docking results were supported by dynamic stability analysis. The combined computational results support rosmariquinone as a potential neuroprotective lead compound for AD treatment.

METHODS: Pharmacokinetic and toxicity profiling of 22 phytoconstituents was performed using Swiss ADME and ProTox III software. Target prediction and construction of the phytoconstituent-disease target-gene interaction network were conducted using Swiss Target Prediction, Gene Card and Cytoscape. Pathway enrichment was evaluated via KEGG and GO analysis. Molecular docking of all shortlisted phytoconstituents against AD-related targets was carried out using AutoDock Vina, while 500 ns molecular dynamics simulations were performed using the Desmond module of the Schrödinger Suite to assess complex stability, RMSD, RMSF and hydrogen-bond fluctuation.},
}

*Alzheimer Disease/drug therapy
*Molecular Docking Simulation
*Neuroprotective Agents/chemistry/pharmacology/pharmacokinetics/therapeutic use
Molecular Dynamics Simulation
Network Pharmacology
Humans
*Plants, Medicinal/chemistry
*Phytochemicals/chemistry/pharmacology/pharmacokinetics

@article {pmid41973471,
year = {2026},
author = {Agnello, L and Ciaccio, AM and Del Ben, F and Gambino, CM and Piccoli, T and Midiri, M and Scazzone, C and Masucci, A and Tamburello, M and Ciaccio, M},
title = {Evaluation of Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) in Cerebrospinal Fluid, Serum, and Plasma Using the Fully Automated Lumipulse Platform.},
journal = {Journal of clinical laboratory analysis},
volume = {},
number = {},
pages = {e70217},
doi = {10.1002/jcla.70217},
pmid = {41973471},
issn = {1098-2825},
abstract = {BACKGROUND: In this study, we first evaluated the relationship between sTREM2 concentrations in CSF, serum, and plasma of Alzheimer's disease (AD) patients using the newly developed Lumipulse G sTREM2 assay.

METHODS: sTREM2 was measured by the fully automated Lumipulse G1200 platform (Fujirebio). Associations and agreement between matrices were assessed using Passing-Bablok regression, Spearman correlation, and Bland-Altman analyses. Sub-analyses explored the influence of disease stage and tau pathology.

RESULTS: Median sTREM2 concentrations were highest in CSF, followed by serum and plasma. Serum and CSF sTREM2 levels showed a moderate but significant correlation (ρ = 0.32; p = 0.0012), although regression analysis indicated poor linearity. In contrast, serum and plasma sTREM2 levels were strongly correlated (ρ = 0.74; p < 0.001). The association between CSF and serum sTREM2 levels was independent of total and phosphorylated tau. Notably, a strong CSF-serum correlation was observed in the MCI due to AD group (ρ = 0.74) but was completely lost in overt AD dementia, demonstrating a clear disease stage-dependent relationship.

CONCLUSION: CSF and blood sTREM2 capture partly distinct biological processes and show limited overall agreement. While serum and plasma sTREM2 are closely related, they are not interchangeable.},
}

@article {pmid41973509,
year = {2026},
author = {Lin, Y and Garcia-Ptacek, S and Eriksdotter, M and Xu, H},
title = {Authors' Reply: Do Amyloid and Tau Ratios Mitigate the Impact of Reduced eGFR on Blood Alzheimer's Biomarkers?.},
journal = {Journal of the American Society of Nephrology : JASN},
volume = {},
number = {},
pages = {},
pmid = {41973509},
issn = {1533-3450},
}

@article {pmid41973513,
year = {2026},
author = {Yin, Y and Zhang, L},
title = {Do Amyloid and Tau Ratios Mitigate the Impact of Reduced eGFR on Blood Alzheimer's Biomarkers?.},
journal = {Journal of the American Society of Nephrology : JASN},
volume = {},
number = {},
pages = {},
pmid = {41973513},
issn = {1533-3450},
}

@article {pmid41973520,
year = {2026},
author = {Franco Rocha, OY and Janelsins, MC and Magnuson, A},
title = {Decision-making and treatment planning for older adults with pre-existing cognitive impairment and cancer.},
journal = {Current opinion in supportive and palliative care},
volume = {},
number = {},
pages = {},
doi = {10.1097/SPC.0000000000000804},
pmid = {41973520},
issn = {1751-4266},
abstract = {PURPOSE OF REVIEW: The review aims to synthesize the current evidence on decision-making and cancer treatment planning for older adults with pre-existing cognitive impairment, Alzheimer's disease, and other related dementias.

RECENT FINDINGS: Current decision-making practices are not standardized, and evidence suggests that oncology physicians conduct burden-benefit analyses to guide treatment planning. There was a consensus on the importance of involving caregivers into the decision-making process. However, caregivers experience feelings of anxiety, uncertainty, and extra burden when deciding between treatment options and providing care. Nursing home staffs were frequently excluded from the decision-making process and were perceived as unprepared to identify and manage cancer symptoms. The planning and provision of care for this population can be guided by a comprehensive geriatric assessment (CGA). CGA can inform the decision-making process based on the patient's functionality and caregiver's resources, facilitate management of cancer care, guide the identification and management of cancer symptoms, and assist communication with patients and their caregivers.

SUMMARY: Decision-making and treatment planning for older adults with cancer and pre-existing cognitive impairment lacks standardization. CGA offers a standardized approach to guide treatment decisions, manage symptoms, and coordinate care by highlighting the needs and resources of patients and caregivers.},
}

@article {pmid41973724,
year = {2026},
author = {Li, H and Wu, X and Wu, G and Guo, J and Nie, Z and Sheng, Q},
title = {Gastrodin Alleviates Tau Hyperphosphorylation Associated with AKT/GSK-3β Signaling Changes in an Alzheimer's Disease Cell Model.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {229},
pages = {},
doi = {10.3791/70432},
pmid = {41973724},
issn = {1940-087X},
mesh = {Humans ; *Benzyl Alcohols/pharmacology ; Glycogen Synthase Kinase 3 beta/metabolism ; *tau Proteins/metabolism ; *Glucosides/pharmacology ; *Alzheimer Disease/metabolism/drug therapy/pathology ; Signal Transduction/drug effects ; Cell Line, Tumor ; *Proto-Oncogene Proteins c-akt/metabolism ; Phosphorylation/drug effects ; Apoptosis/drug effects ; *Glycogen Synthase Kinase 3/metabolism ; },
abstract = {Alzheimer's disease (AD) is a common neurodegenerative disease for which there are currently limited effective drugs. As the principal bioactive component derived from Gastrodia elata, Gastrodin (GAS) has shown clear therapeutic potential for treating AD; however, the molecular mechanism of its action remains to be elucidated. In this study, we aim to investigate the mechanism of the effect of GAS on AD model cells. Network pharmacology is employed to analyze the targets and signaling pathways affected by GAS in AD. An AD cell model is constructed by inducing human neuroblastoma SH-SY5Y cells with Okadaic acid (OA). Cell viability was assessed using the CCK-8 assay, while the levels of SOD, MDA, and T-AOC were measured. Apoptosis rate was determined through Annexin V-FITC/PI double staining, and expression of apoptosis-related factors, as well as AKT, GSK-3β, p-Tau (Ser396), and p-Tau (Thr181), was analyzed using RT-qPCR and Western blotting techniques. Network pharmacology analysis suggests that GAS has the potential to regulate cellular apoptosis and associated signaling pathways, including PI3K/AKT. Our experiments demonstrate that GAS can inhibit MDA levels, increase T-AOC and SOD in the AD model cells, and reduce cell apoptosis. Western blotting results indicate that GAS mitigates OA's inhibitory effects on p-AKT (Ser473) and p-GSK-3β (Ser9) expression. Additionally, it attenuates the overexpression of p-Tau (Ser396) and p-Tau (Thr181), suppresses Bax expression, and enhances Bcl-2 expression. GAS demonstrates the ability to ameliorate oxidative stress injury induced by OA and mitigate apoptosis. GAS may suppress Tau hyperphosphorylation, which is associated with changes in the AKT/GSK-3β signaling pathway, thereby exerting potential neuroprotective effects.},
}

Humans
*Benzyl Alcohols/pharmacology
Glycogen Synthase Kinase 3 beta/metabolism
*tau Proteins/metabolism
*Glucosides/pharmacology
*Alzheimer Disease/metabolism/drug therapy/pathology
Signal Transduction/drug effects
Cell Line, Tumor
*Proto-Oncogene Proteins c-akt/metabolism
Phosphorylation/drug effects
Apoptosis/drug effects
*Glycogen Synthase Kinase 3/metabolism

@article {pmid41973869,
year = {2026},
author = {Prakash, RS and Phansikar, M and Fisher, ME and Dove, S and Andridge, R and Scharre, D and Wright, KD and Head, E and O'Callaghan, C and Meyerson, QK and Duraney, EJ and Schroeder, M and Chakrapani, N and Grant, EK and Jones, T and Teng, J and Esterman, M and Smyth, JM and Gregoire, T and Malhas, R},
title = {Feasibility of Internet-Based Mind-Body Training for Adults With Subjective Cognitive Decline: Protocol for a Randomized Controlled Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e86276},
doi = {10.2196/86276},
pmid = {41973869},
issn = {1929-0748},
mesh = {Humans ; *Cognitive Dysfunction/therapy/psychology ; Middle Aged ; Feasibility Studies ; Internet ; Aged ; Male ; Mindfulness/methods ; *Internet-Based Intervention ; Female ; *Mind-Body Therapies/methods ; Randomized Controlled Trials as Topic ; Alzheimer Disease ; },
abstract = {BACKGROUND: In the United States, the prevalence of Alzheimer disease (AD) is projected to double over the next 30 years, with associated familial and societal costs estimated at US $1 trillion annually if current trends continue. Although pharmacological treatments of AD are showing promise, the adoption of healthy lifestyle behaviors, particularly during the preclinical phase of AD, may reduce dementia rates by up to 45%. Subjective cognitive decline (SCD), defined as persistent self-perceived declines in cognitive functioning compared with previously normal cognitive abilities, has been identified as a potential preclinical stage of AD.

OBJECTIVE: This randomized controlled trial aims to evaluate the feasibility and acceptability of an internet-based, asynchronous mindfulness-based stress reduction program compared with an active control group (an internet-based lifestyle education program). Secondary objectives include examining preliminary effects of each intervention on SCD, plasma-based biomarkers of amyloid and tau pathology, and everyday mind-wandering.

METHODS: Sixty adults aged 50 years and older will be screened for SCD in the absence of objective cognitive impairment, based on the Uniform Data Set Neuropsychological Battery (version 3.0) from the National Alzheimer's Coordinating Center. Eligible and consenting participants will complete behavioral and imaging-based tasks of sustained attention and mind-wandering, as well as blood draws at baseline and after the 8-week intervention. After baseline assessments, participants will be randomized to either an internet-based, asynchronous mindfulness-based stress reduction program or the internet-based lifestyle education program. Both programs have been adapted from our manualized in-person programs and refined through focus group interviews with the target population.

RESULTS: The study was funded in April 2024. Phase 1 focused on iterative development of the 2 programs based on focus group feedback. Recruitment for the randomized controlled trial (internet-based mind-body training trial) began in June 2025 and is ongoing. Recruitment is expected to conclude in September 2026, with data collection ending in December 2026.

CONCLUSIONS: Behavioral, lifestyle-based interventions that emphasize experiential practices show promise as preventative strategies to prevent decline in cognitive and brain health. Yet, there remain significant barriers to engaging with in-person programs, including limited accessibility, time and schedule constraints, and travel logistics. The internet-based mind-body training trial will evaluate the feasibility and acceptability of 2 fully online, mind-body training programs for adults at risk for AD. Future Stage II and Stage III studies will be necessary to establish the efficacy of these programs for improving AD biomarkers and cognitive outcomes and their broader dissemination to adults noticing subtle changes in cognitive functioning.},
}

Humans
*Cognitive Dysfunction/therapy/psychology
Middle Aged
Feasibility Studies
Internet
Aged
Male
Mindfulness/methods
*Internet-Based Intervention
Female
*Mind-Body Therapies/methods
Randomized Controlled Trials as Topic
Alzheimer Disease

@article {pmid41974093,
year = {2026},
author = {Sternberg, Z and Podolsky, RE and Yu, J and Hua, S and Halvorsen, S and Schaller, BJ},
title = {Hypolipidemics reduce the rate of Alzheimer's disease development and dementia progression: A cohort study linked with genetic and neuropathological analyses.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {6},
pages = {100555},
doi = {10.1016/j.tjpad.2026.100555},
pmid = {41974093},
issn = {2426-0266},
abstract = {BACKGROUND: High cholesterol contributes to the development and progression of dementia due to both Alzheimer's disease (A.D.) and vascular pathology. However, the effects of lipid-lowering regimen (LLR) on cognitive dysfunction and brain neuropathology are unknown.

OBJECTIVE: To investigate the effect of LLR on the conversion from normal to mild cognitive impairment (MCI), indicated by CDR-SOB of >0-2.5 (MCI), and the progression to dementia, indicated by CDR-SOB =>3 (10-year follow-up) and LLR effect on the rate of survival (15-year follow-up). Participants were stratified by age (≤70 years and >70 years), gender, and the presence of at least one copy of the APOE4 allele. We also analyzed the effect of LLR on brain neuropathology in participants, indicated by Braak staging, hippocampal atrophy, and CSF levels of total Tau. The differential effect of LLR, with or without cerebrovascular disease, lacunar infarct, or cystic infarction in the cognitive network, was analyzed.

METHODS: We have analyzed the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS).

RESULTS: In participants with CDR-SOB of >0-2.5, the use of hypolipidemic agents was associated with a reduced yearly increase in the CDR-SOB scores by 0.0088 (0.0038, 0.0138) unit (P < 0.001). This effect was more pronounced in participants with CDR-SOB =>3 showing a reduced yearly increase in the CDR-SOB scores by 0.1733 (0.1441, 0.2025) unit (P < 0.001) in LLR-users compared to non-users, and an increased rate of survival [HR: 0.822 (0.746, 0.906). P = 0.001]. The pattern persisted when participants were stratified based on age, gender, and the presence of APOE4. LLR had no significant effect on Braak staging scores, hippocampal atrophy, and total CSF Tau level, and was independent of the presence or absence of cerebrovascular disease, lacunar infarct, and cystic infarction in cognitive network.

CONCLUSION: Our results have implications for delaying cognitive dysfunction and halting the progression of dementia, regardless of the etiology being related to AD or vascular pathology.},
}

@article {pmid41974215,
year = {2026},
author = {Rossner, P and Libalova, H and Sima, M and Cervena, T and Simova, Z and Vrbova, K and Ambroz, A and Rossnerova, A and Novakova, Z and Elzeinova, F and Vimrova, A and Klema, J and Koivisto, AM and Penttilä, E and Dittrich, L and Vojtisek, M and Pechout, M and Kanninen, KM and Vojtisek-Lom, M},
title = {Molecular alterations in human olfactory mucosal cells from healthy individuals and individuals with Alzheimer's disease induced by real-world ambient air.},
journal = {Environmental toxicology and pharmacology},
volume = {},
number = {},
pages = {105019},
doi = {10.1016/j.etap.2026.105019},
pmid = {41974215},
issn = {1872-7077},
abstract = {Ambient air pollution is a global problem linked to various diseases, including neurodegenerative disorders. Using a mobile exposure system, we investigated the molecular changes in human olfactory cleft mucosal (hOM) cells from healthy individuals and Alzheimer's disease (AD) patients exposed to real-world ambient air. Samples were exposed at the air-liquid interface in a low-pollution Background site and a moderately polluted (within recommended limits) Industrial site. We assessed immune response-related molecules, lipid peroxidation and global RNA expression. Leukemia-inhibitory factor (LIF) increased in healthy, but not AD samples at the Industrial locality, while lipid peroxidation levels remained unchanged. Compared with a blank control, significant enrichment of biological processes and KEGG pathways occurred only in Industrial site samples. In healthy cells, neurodegeneration-related pathways were significantly affected, whereas AD samples showed enhanced inflammation-related responses. These findings suggest that even pollution within recommended limits can induce molecular changes potentially contributing to neurodegenerative disease development.},
}

@article {pmid41974257,
year = {2026},
author = {Kushwaha, S and Karunakaran, S},
title = {Early Dorsal Hippocampal Catecholaminergic Vulnerability Is Associated with Sex-Specific Susceptibility to Proactive Interference in APP/PS1 Mice.},
journal = {Behavioural brain research},
volume = {},
number = {},
pages = {116208},
doi = {10.1016/j.bbr.2026.116208},
pmid = {41974257},
issn = {1872-7549},
abstract = {Interference is a major contributor to early memory decline in Alzheimer's disease (AD), yet standard assays often fail to detect vulnerability at pre-plaque stages; to address this, male and female 2-month-old APP/PS1 and wild-type mice were assessed using a proactive-interference-modified novel object recognition (PI-NOR) paradigm, alongside quantitative analysis of tyrosine hydroxylase-positive (TH[+]) catecholaminergic axon terminals across dorsal and ventral hippocampal subregions. Despite typically intact recognition at this age, PI selectively impaired recognition memory in male APP/PS1 mice, while females retained stable performance, revealing a sex-specific susceptibility to interference. This behavioral deficit in males was paralleled by a reduction in TH[+] catecholaminergic terminals confined to the dorsal hippocampus, with no comparable loss observed in females. Augmenting β-adrenergic signaling with chronic isoproterenol administration restored recognition performance in male APP/PS1 mice under PI conditions without altering baseline NOR. These findings establish PI as a sensitive probe of latent recognition instability and indicate that reduced dorsal hippocampal catecholaminergic input is associated with interference-related vulnerability in male APP/PS1 mice.},
}

@article {pmid41974265,
year = {2026},
author = {Oğuztüzün, Ç and Gao, Z and Li, J and Qi, X and Koyutürk, M and Xu, R},
title = {Learning to take it personally: Precision drug repurposing through patient-specific loss on knowledge graphs using Biobank data.},
journal = {Journal of biomedical informatics},
volume = {},
number = {},
pages = {105039},
doi = {10.1016/j.jbi.2026.105039},
pmid = {41974265},
issn = {1532-0480},
abstract = {OBJECTIVE: Precision medicine requires drug repurposing methods that adapt to individual patient profiles while working within regulatory frameworks. Existing approaches apply uniform models to all patients, only using individual factors as inputs or filters.

METHODS: Our framework instead integrates patient-specific profiles into the learning algorithm through a customized loss function. We combine standard link prediction with UK Biobank data-integrating polygenic risk scores, biomarker expressions, and medical history.

RESULTS: Evaluated on a biomedical knowledge graph connecting 61,000+ entities through 1.2+ million relations, our approach improves drug repurposing quality with AUPRC improvements ranging from 1.3× to 5.4× across patients. Case studies on Alzheimer's Disease patients reveal drug candidates with stronger AD evidence and patient-specific mechanisms. Our loss function identifies influential diseases and biomarkers for each patient, enhancing interpretability while providing biologically relevant recommendations tailored to individual profiles.

CONCLUSION: This approach represents a fundamental shift from treating personalization as data preprocessing to embedding it within the learning objective itself.},
}

@article {pmid41974315,
year = {2026},
author = {Lee, SY and Kim, JC and Song, J and Lee, Y and Kim, M and Chang, SH and Kim, JS and Park, JS and Choi, MR and Lee, SR},
title = {KBN2201 attenuates Aβ pathology, and neuroinflammation while promoting neuroprotective and neurogenesis-related changes in a late-stage 5xFAD mouse model of Alzheimer's disease.},
journal = {Neuropharmacology},
volume = {},
number = {},
pages = {110970},
doi = {10.1016/j.neuropharm.2026.110970},
pmid = {41974315},
issn = {1873-7064},
abstract = {Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) accumulation, neuroinflammation, neuronal loss, and cognitive decline. Here, we report that KBN2201, a derivative of 2-hydroxy-4-(trifluoromethyl)benzoic acid, exerts multi-target effects in 5xFAD mice. To evaluate its efficacy at a late disease stage, daily oral administration of KBN2201 (5 or 20 mg/kg) was initiated in 9-month-old 5xFAD mice and continued for three months. KBN2201 significantly reduced hippocampal amyloid precursor protein C-terminal fragments (APP-CTFs), indicating decreased accumulation of APP-derived fragments. In addition, KBN2201 lowered insoluble Aβ42 levels, supporting on overall reduction in amyloid burden. The compound also reduced both fibrillar and total Aβ plaque burden in the cortex and hippocampus, as demonstrated by thioflavin S and 4G8 staining. Astrocytic and microglial activation was significantly suppressed. Preservation of the hippocampal CA1 region and cortical dendritic structure was observed. In addition, markers associated with neurogenesis were increased in the subventricular zone (SVZ) and hippocampus, as indicated by elevated Ki67 and doublecortin (DCX) levels. These effects were accompanied by improved spatial working memory in the Y-maze test and enhanced recognition memory in the novel object recognition (NOR) test, with greater effects observed at the 5 mg/kg dose. Together, these findings suggest that KBN2201 mitigates AD-related pathology and improves cognitive function, supporting its potential as a multi-target therapeutic candidate for AD.},
}

@article {pmid41974642,
year = {2026},
author = {Xing, L and Liu, A and Gao, W and Li, J and Yao, M and Song, J and Duan, P and Li, H},
title = {Beyond the neuron: Exosomes as intercellular modulators of mitochondrial networks in the pathogenesis and treatment of Alzheimer's disease.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71330},
doi = {10.1002/alz.71330},
pmid = {41974642},
issn = {1552-5279},
support = {82105035//National Natural Science Foundation of China/ ; LH2023H064//Nature Science Foundation of Heilongjiang Province/ ; ZHY2024-304//Research Project of the Traditional Chinese Medicine Administration of Heilongjiang Province/ ; },
mesh = {Humans ; *Exosomes/metabolism ; *Alzheimer Disease/metabolism/therapy/pathology ; *Mitochondria/metabolism ; *Neurons/metabolism ; Animals ; Autophagy/physiology ; },
abstract = {Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by β-amyloid deposition, hyperphosphorylated tau protein, and progressive neuronal loss. Mitochondria form a dynamic interconnected network within the central nervous system, and their dysfunction plays a central role in AD, involving oxidative stress, kinetic dysregulation, and impaired mitochondrial autophagy. As key mediators of intercellular communication, exosomes carry bioactive components that regulate mitochondrial function in recipient cells. This review summarizes advances in research on exosomes as coordinators of the mitochondrial network in the central nervous system, regulating mitochondrial quality control across different neuronal cell types. It systematically outlines the molecular mechanisms by which exosomes modulate mitochondrial function in AD through regulating mitochondrial biogenesis, fusion-fission dynamics, mitochondrial autophagy, and related signaling pathways. Furthermore, it explores the potential of engineered exosome-based targeted therapies for AD intervention, aiming to provide a theoretical foundation and research direction for developing novel therapeutic strategies targeting mitochondrial dysfunction.},
}

Humans
*Exosomes/metabolism
*Alzheimer Disease/metabolism/therapy/pathology
*Mitochondria/metabolism
*Neurons/metabolism
Animals
Autophagy/physiology

@article {pmid41974948,
year = {2026},
author = {Ünlütürk, ZG and Madanoğlu, N and Atıcı, E},
title = {Effectiveness of individualized music listening on functional and cognitive status in advanced Alzheimer's disease.},
journal = {Zeitschrift fur Gerontologie und Geriatrie},
volume = {},
number = {},
pages = {},
pmid = {41974948},
issn = {1435-1269},
abstract = {BACKGROUND AND OBJECTIVE: Individualized music listening, linked to personal memories has been suggested as a supportive nonpharmacological approach but its effects in advanced-stage patients are not well-established. This study aimed to investigate the effects of individualized music listening on cognitive and functional status in individuals with advanced-stage Alzheimer's disease.

INTERVENTION AND METHODS: In this study 54 patients were randomly assigned to an individualized music listening intervention group (IMLIG) or a control group (CG). The IMLIG listened to personally meaningful music, while the CG listened to Shostakovich's Jazz Suite No. 2, 3 times per week for 12 weeks. Cognitive and functional outcomes were assessed using the mini-mental state examination (MMSE), functional independence measure (FIM), clock drawing test (CDT) and frontal assessment battery (FAB) at baseline, week 6 and week 12.

RESULTS: The results showed significant improvements in mental status and cognitive functions in the IMLIG (p < 0.05), while functional independence declined despite the intervention (p < 0.05). The CG demonstrated only limited cognitive changes and no improvement in functional independence.

DISCUSSION: These findings suggest that individualized music listening provides short-term benefits for cognitive awareness and visuomotor skills but could be insufficient to counter the progressive functional decline of Alzheimer's disease.},
}

@article {pmid41974983,
year = {2026},
author = {Liu, X and Wang, X and Xie, R and Liu, Z and Wang, B and Zhai, H},
title = {Explainable machine learning for predicting mechanical ventilation in Alzheimer's patients with pneumonia: a SHAP-guided XGBoost nomogram based on MIMIC-IV.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-48214-x},
pmid = {41974983},
issn = {2045-2322},
support = {Project No. 2025-GMKY-14//Qinghai University/ ; },
abstract = {Alzheimer's disease (AD) patients are particularly vulnerable to pneumonia and subsequent respiratory failure due to neurodegeneration-induced dysphagia and immunosenescence. Accurate prediction of mechanical ventilation (MV) need in this population remains a critical but unmet clinical challenge. This retrospective cohort study utilized the MIMIC-IV database to identify 793 critically ill AD patients diagnosed with pneumonia. Clinical variables were extracted and filtered using LASSO regression and multivariate logistic regression to identify key predictors. Five machine learning algorithms, including XGBoost, were constructed and compared to evaluate MV prediction performance. Model interpretability was enhanced using SHAP analysis, and a nomogram was developed based on the best-performing model. Among the included patients, 213 (26.9%) required mechanical ventilation during ICU admission. The XGBoost model outperformed all other algorithms, achieving the highest AUC in both the training (0.849) and validation (0.744) sets, as well as superior F1-score (0.507) and balanced accuracy (0.776). SHAP analysis identified COPD, temperature, and gender as the most influential predictors. The final nomogram incorporating seven key variables (Gender, AKI, COPD, OASIS, Temperature, PLT, and antibiotic use) achieved robust discrimination (validation Set AUC = 0.780), excellent calibration, and consistent clinical benefit in decision curve analysis. The derived NomoScore stratified patients into quartiles with escalating MV risk (p < 0.001), and retained predictive accuracy with Cohen's kappa values of 0.40 (training) and 0.363 (validation). The model demonstrated superior net benefit over conventional scoring systems and has the potential to support bedside decision-making in cognitively impaired ICU populations. This study presents a validated, interpretable XGBoost-based model and clinical nomogram for predicting mechanical ventilation risk in AD patients with pneumonia. The framework offers a precision tool to aid ICU triage and guide ventilatory strategies.},
}

@article {pmid41831526,
year = {2026},
author = {Kelliher, JC and Engeland, CG and Graham-Engeland, JE and Katz, M and Kessler, C and Shearer, GC},
title = {Oxylipin composition of high-density lipoprotein is altered in men and Hispanic adults with mild cognitive impairment.},
journal = {Journal of lipid research},
volume = {67},
number = {4},
pages = {101021},
doi = {10.1016/j.jlr.2026.101021},
pmid = {41831526},
issn = {1539-7262},
abstract = {High-density lipoprotein (HDL) oxylipins are potent inflammatory mediators. HDL dyshomeostasis and inflammation increase mild cognitive impairment (MCI) and dementia risk, which vary by gender and race/ethnicity. It is unknown whether and how HDL oxylipin profiles differ between non-MCI and MCI individuals, or if potential differences are gender- and/or race/ethnicity dependent. In this targeted lipidomics study, we profiled plasma HDL oxylipins in older (70+) adults (N = 222) with or without MCI to determine how HDL oxylipin composition relates to cognitive impairment status. HDL oxylipin concentrations were analyzed by cognitive status, gender, and race/ethnicity (non-Hispanic Black, Hispanic, and non-Hispanic white). We found a gender- and race/ethnicity-specific association between MCI and lower HDL oxylipin content, which was independent of overall HDL-c concentrations. The HDL of MCI men contained lower amounts of anti-inflammatory and vasodilatory omega (ω)3 EPA C20:5ω3-derived hydroxyeicosapentaenoic acids (HEPEs) and DHA C22:6ω3-derived hydroxydocosahexaenoic acids than that of non-MCI men. Similarly, Hispanic participants with MCI had lower HDL concentrations of EPA C20:5ω3-derived HEPEs and DHA C22:6ω3-derived hydroxydocosahexaenoic acids than non-MCI Hispanic participants. Higher HDL concentrations of EPA C20:5ω3-derived HEPEs appeared protective against MCI in both men and Hispanic individuals. Further, higher oxylipin concentrations within HDL correlated with better cognition in non-Hispanic white women. This work identifying altered HDL oxylipin composition in MCI highlights a novel dysregulated lipid signaling pathway in cognitive decline. Reduced anti-inflammatory and vasodilatory ω3 oxylipins within HDL in MCI men and Hispanic individuals provide molecular evidence linking together HDL functionality, inflammation, and dementia risk.},
}

@article {pmid41964066,
year = {2026},
author = {Zehra, S and Rai, S and Rani, K and Choudhury, SD and Rai, H and Bhowmik, S and Mohan, N and Gupta, A and Chatterjee, P and Reddy, TJ and Rani, N and Modi, GP and Nikolajeff, F and Kumar, S},
title = {Stress-induced alteration of small extracellular vesicles drives amyloid-beta sequestration and exacerbates Alzheimer's disease pathogenesis.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02028-1},
pmid = {41964066},
issn = {1758-9193},
}

@article {pmid41964075,
year = {2026},
author = {Andreozzi, E and Yagi, T and Wildsmith, K and Rawal, S and Horie, K and Boyd, P and Takahashi, E and Barthélemy, NR and Aluri, J and Charil, A and Reilhac, A and Gordon, BA and Flores, S and Verbel, D and Sauter, N and Benzinger, TLS and McDade, E and Mummery, C and , and , and Zhou, J and Bateman, RJ and Reyderman, L},
title = {Etalanetug (E2814) in dominantly inherited Alzheimer's disease: an open-label phase 1b/2 study to assess safety and target engagement in participants with mild to moderate cognitive impairment.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02047-y},
pmid = {41964075},
issn = {1758-9193},
abstract = {INTRODUCTION: Etalanetug (E2814) is designed to delay the clinical progression of Alzheimer's disease (AD) by binding to the microtubule binding region (MTBR) of tau implicated in seeding and spreading of tau pathology. Dominantly inherited Alzheimer's disease (DIAD) is a rare form of the disease (< 1%), having similar changes in the tau distribution and pathology to sporadic AD. Herein, we report the safety, pharmacology and biomarker results of the etalanetug Study 103 in DIAD patients.

METHODS: Study 103 enrolled participants with mild-to-moderate cognitive impairment due to DIAD who received etalanetug intravenously every 4 weeks escalating from 750 mg, 1500 mg, 3000 mg, to 4500 mg. After ascending to 4500 mg, patients received 4500 mg for up to 108 weeks. Tau pathology biomarkers, ptau217 and MTBR-tau243 were measured in CSF. Additional assessments included tau PET ([[18]F]MK-6240) and MRI. Pharmacodynamic effects of etalanetug on biomarkers were evaluated. Untreated participants from the DIAN Observational and DIAN-TU studies trial served as natural history controls.

RESULTS: Overall, 8 participants enrolled in Study 103. Etalanetug reduced concentrations of ptau217 30.4% after 12 weeks (n = 7), 48.6% at 36 weeks (n = 5), and 57.9% at 108 weeks (n = 2). Etalanetug treatment reduced concentrations of MTBR-tau243 by 50.6% in DIAD participants (n = 7) after 12 weeks of treatment. Maximal reduction in MTBR-tau243 levels (71.6%) was observed at week 36 (n = 4) and was sustained to 108 weeks (n = 2). In healthy volunteers who lack tau pathology, etalanetug had no effect on MTBR-tau243 or ptau217 after 12 weeks of treatment. Three DIAD patients had tau PET acquired at week 60 and week 108. The data indicate that the tau PET SUVr signal remains stable overall, with a trend towards decrease over time. At 108 weeks, no tau accumulation was observed via tau PET in any of the 3 patients. Three participants experienced treatment-related adverse events (AEs) with the 3000 mg dose; additionally, 5 serious AEs total were reported in 3 participants.

DISCUSSION: Etalanetug treatment in these symptomatic participants with DIAD was tolerated across dose levels, and immunogenicity was found to be minimal. Etalanetug demonstrated effects on both hyperphosphorylated tau and tau tangle pathology. Taken together, the data support continued evaluation of etalanetug as an AD disease-modifying therapy.

TRIAL REGISTRATION: NCT04971733 (registration date: 2021-07-20).},
}

@article {pmid41964371,
year = {2026},
author = {Lin, JY and Huang, ZB and Fang, EF and Lu, G},
title = {STUB1-VCP/p97 limits PINK1 overaccumulation to safeguard mitophagy and memory.},
journal = {Autophagy},
volume = {},
number = {},
pages = {},
doi = {10.1080/15548627.2026.2658848},
pmid = {41964371},
issn = {1554-8635},
abstract = {PINK1 serves as the central regulator of PINK1-PRKN-mediated mitophagy, and its precise regulation is critical for efficient mitochondrial clearance. Although the cleavage of PINK1 and its subsequent degradation via the N-end rule pathway under basal conditions are well understood, how full-length PINK1 stability is regulated following mitochondrial damage has remained elusive. In our recent study, we identified the STUB1-VCP/p97 axis as a mechanism that fine-tunes full-length PINK1 levels during mitophagy. We demonstrate that STUB1 functions as an E3 ubiquitin ligase that catalyzes K48-linked polyubiquitination of full-length PINK1, which is subsequently recognized and extracted by VCP/p97 for proteasomal degradation. Disruption of this axis results in excessive accumulation of full-length PINK1, accelerated turnover of PRKN, and impaired mitophagy. Moreover, we find that this regulatory mechanism is compromised in the brains of patients with Alzheimer disease (AD), and its disruption leads to neuronal mitophagy defects and impaired associated learning capability in C. elegans. These findings demonstrate that the STUB1-VCP/p97 complex fine-tunes PINK1 levels to ensure efficient mitophagy and preserve mitochondrial homeostasis.Abbreviations: AD, Alzheimer disease; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; MPP, mitochondrial processing peptidase; MQC, mitochondrial quality control; OMM, outer mitochondrial membrane; OPTN, optineurin; PARL, presenilin associated rhomboid like; PINK1, PTEN induced kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; SILAC, stable isotope labeling by amino acids in cell culture; STUB1, STIP1 homology and U-box containing protein 1; TPR, tetratricopeptide repeat; VCP/p97, valosin containing protein; WIPI2, WD repeat domain, phosphoinositide interacting 2.},
}

@article {pmid41964394,
year = {2026},
author = {Abdullah, LB and Zhang, F and Petersen, M and Hall, J and Handen, BL and Mapstone, M and Christian, B and Head, E and Harley, S and Andrews, H and Lee, JH and Tudorascu, D and Hom, C and Zaman, S and Brickman, AM and Rosas, D and Cohen, A and Harp, JP and Schmitt, F and Ptomey, L and Burns, JM and Lott, IT and Lai, F and Laymon, C and Cruchaga, C and O'Bryant, S and Ances, BM},
title = {The association between APOE 𝜀4 carrierships and the detection of amyloid positivity using an Alzheimer's disease proteomic blood test in asymptomatic Down syndrome.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {22},
number = {4},
pages = {e71338},
pmid = {41964394},
issn = {1552-5279},
support = {U01 AG051406/AG/NIA NIH HHS/United States ; U01 AG051412/AG/NIA NIH HHS/United States ; U19 AG068054/AG/NIA NIH HHS/United States ; //Investigation of Co-occurring conditions across the Lifespan to Understand Down syndrome (NIH INCLUDE Project)/ ; //Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; },
mesh = {Humans ; Male ; *Down Syndrome/genetics/blood/diagnostic imaging ; Female ; *Apolipoprotein E4/genetics ; Proteomics ; Middle Aged ; Adult ; Cross-Sectional Studies ; Biomarkers/blood ; *Amyloid beta-Peptides/blood ; *Alzheimer Disease/blood/genetics ; tau Proteins/blood ; Positron-Emission Tomography ; Neurofilament Proteins/blood ; Glial Fibrillary Acidic Protein/blood ; Peptide Fragments/blood ; Heterozygote ; Aniline Compounds ; },
abstract = {INTRODUCTION: This study evaluates plasma-based proteomic profiles for predicting amyloid positivity in adults with Down syndrome (DS) and examines the impact of apolipoprotein E ε4 (APOE ε4) on test performance.

METHODS: Cross-sectional data from 290 adults with DS were analyzed using single molecule array (SIMOA) technology to measure plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181, and total tau. Amyloid burden was quantified using Pittsburgh Compound B and (18)F-florbetapir Aβ positron emission tomography. Support vector machine analyses were conducted with biomarkers as predictors and age, sex, and APOE ε4 carrier status as covariates.

RESULTS: Age, GFAP, and NfL contributed the most to the model performance. The proteomic profile achieved an area under the curve (AUC) of 96% in models with and without APOE ε4.

DISCUSSION: These findings suggest that plasma proteomic biomarkers can effectively identify amyloid positivity in adults with DS and may support clinical triage, monitoring, and selection for clinical trials, independent of APOE ε4 status.},
}

Humans
Male
*Down Syndrome/genetics/blood/diagnostic imaging
Female
*Apolipoprotein E4/genetics
Proteomics
Middle Aged
Adult
Cross-Sectional Studies
Biomarkers/blood
*Amyloid beta-Peptides/blood
*Alzheimer Disease/blood/genetics
tau Proteins/blood
Positron-Emission Tomography
Neurofilament Proteins/blood
Glial Fibrillary Acidic Protein/blood
Peptide Fragments/blood
Heterozygote
Aniline Compounds

@article {pmid41964654,
year = {2026},
author = {Stögmann, E and König, T},
title = {Response to Amalia.},
journal = {Genetics in medicine : official journal of the American College of Medical Genetics},
volume = {28},
number = {4},
pages = {101689},
doi = {10.1016/j.gim.2026.101689},
pmid = {41964654},
issn = {1530-0366},
}

@article {pmid41964656,
year = {2026},
author = {Amalia, R},
title = {Correspondence on "Assessing family history and approaches for identifying patients with dementia with diagnostically significant genetic findings" by König et al.},
journal = {Genetics in medicine : official journal of the American College of Medical Genetics},
volume = {28},
number = {4},
pages = {101688},
doi = {10.1016/j.gim.2026.101688},
pmid = {41964656},
issn = {1530-0366},
}

@article {pmid41964788,
year = {2026},
author = {Zhang, R and Dong, X and Pei, G and Huang, S},
title = {Engineered Alzheimer Organoids Validate the Link Between Intracellular and Soluble p-Tau Biomarkers and Highlight the Contribution of Astrocytic Tau.},
journal = {Neuroscience bulletin},
volume = {},
number = {},
pages = {},
pmid = {41964788},
issn = {1995-8218},
abstract = {Soluble phosphorylated tau has become a key biomarker for Alzheimer's disease pathology, yet further mechanistic studies are needed beyond observational investigations to clarify the relationship between soluble p-tau species and intracellular tau pathology. Here, we utilized chimeric human cerebral organoids (chCOs) to generate a series of organoids in which the endogenous MAPT gene was CRISPR/Cas9 edited in different cell types to create phosphorylation-deficient mutants at the AD-associated sites. We found that the APPswe mutation increased tau phosphorylation in both neurons and astrocytes. Notably, astrocyte-specific phosphorylation-deficient mutations of tau in organoids reduced soluble p-tau181 and p-tau217 levels, as detected by single-molecule array. These findings indicate that astrocytic tau plays a substantial role in contributing to the pool of extracellular phosphorylated tau and suggest it may be an overlooked source of AD biomarkers. Moreover, our engineered chCOs offer a versatile platform for exploring how cell-type-specific pathologies correlate with changes in biomarker profiles.},
}

@article {pmid41964801,
year = {2026},
author = {Shteinfer-Kuzmine, A and Nivedita, AK and Santhanam, M and Trishna, S and Swerdlow, RW and Pan, J and Shoshan-Barmatz, V},
title = {Targeting VDAC1 to protect against mitochondria-linked cell death pathways: apoptosis, pyroptosis, ferroptosis, and associated diseases.},
journal = {Apoptosis : an international journal on programmed cell death},
volume = {31},
number = {4},
pages = {},
pmid = {41964801},
issn = {1573-675X},
mesh = {*Voltage-Dependent Anion Channel 1/metabolism/genetics/antagonists & inhibitors ; *Ferroptosis/drug effects ; *Pyroptosis/drug effects ; Animals ; *Mitochondria/metabolism/drug effects ; *Apoptosis/drug effects ; Humans ; Mice ; Reactive Oxygen Species/metabolism ; *Alzheimer Disease/metabolism/genetics/drug therapy/pathology ; Inflammatory Bowel Diseases/metabolism/drug therapy/genetics/pathology ; Mice, Inbred C57BL ; Inflammasomes/metabolism ; },
abstract = {The pathways of programmed cell death (PCD), including apoptosis, pyroptosis, and ferroptosis, are interconnected. They can be activated simultaneously within tissues or cell lines and are often associated with various diseases. Thus, identifying a common player and inhibitor targeting several PCD types is essential. Here, we show that overexpression and oligomerization of the mitochondrial gatekeeper voltage-dependent anion channel 1 (VDAC1) is involved in apoptosis, pyroptosis, and ferroptosis, and specific VDAC1 oligomerization inhibitors, VBIT-4 and VBIT-12, prevented multiple forms of PCD triggered by various stimuli. In addition, they mitigated mitochondrial dysfunction, reduced reactive oxygen species production and intracellular Ca[2][+] levels, preserved mitochondrial-associated hexokinase, and inhibited assembly/activation of the NLRP3 inflammasome. In Alzheimer's disease and inflammatory bowel disease mouse models, VBIT-4 and VBIT-12, respectively, protected against apoptosis, pyroptosis, ferroptosis, and disease-associated pathologies. Thus, we show that VDAC1 oligomerization represents a prime target for VBIT-4 and VBIT-12 that can simultaneously inhibit various PCD forms and diseases associated with enhanced PCD and/or inflammation.},
}

*Voltage-Dependent Anion Channel 1/metabolism/genetics/antagonists & inhibitors
*Ferroptosis/drug effects
*Pyroptosis/drug effects
Animals
*Mitochondria/metabolism/drug effects
*Apoptosis/drug effects
Humans
Mice
Reactive Oxygen Species/metabolism
*Alzheimer Disease/metabolism/genetics/drug therapy/pathology
Inflammatory Bowel Diseases/metabolism/drug therapy/genetics/pathology
Mice, Inbred C57BL
Inflammasomes/metabolism

@article {pmid41964823,
year = {2026},
author = {Ibrahim, KN and Wasim, R and Rahman, E},
title = {HMGB1-mediated neuroinflammation: molecular mechanisms and emerging therapeutic approaches.},
journal = {Inflammopharmacology},
volume = {},
number = {},
pages = {},
pmid = {41964823},
issn = {1568-5608},
abstract = {High mobility group box 1 (HMGB1) has emerged as a central inflammatory mediator linking cellular stress and tissue injury to sustained neuroinflammation in the central nervous system. Although originally characterized as a nuclear chromatin-binding protein, HMGB1 acquires potent pro-inflammatory activity following cytoplasmic translocation and extracellular release, where it functions as a damage-associated molecular pattern. The inflammatory actions of HMGB1 are regulated by its redox state and post-translational modifications, which determine receptor engagement and downstream signaling. Extracellular HMGB1 interacts with pattern-recognition receptors including TLR4/MD-2, the receptor for advanced glycation end products (RAGE), CXCR4, and nucleic acid-sensing Toll-like receptors, leading to activation of NF-κB, MAPK, JAK/STAT, and inflammasome pathways. These cascades amplify cytokine production, glial activation, oxidative stress, blood-brain barrier disruption, and neuronal dysfunction. Dysregulated HMGB1 signaling has been implicated in acute and chronic neurological disorders, including ischemic stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and epilepsy. From a pharmacological perspective, HMGB1 has emerged as a potential therapeutic target, although most supporting evidence currently comes from preclinical studies and further clinical validation is required. Several strategies aimed at attenuating HMGB1-driven inflammation-such as neutralizing antibodies, direct HMGB1 inhibitors including glycyrrhizin, TLR4 and RAGE antagonists, natural anti-inflammatory compounds, and nanotechnology-based delivery systems-have demonstrated beneficial effects in experimental and preclinical models, but clinical validation remains limited. However, clinical translation remains limited by poor blood-brain barrier penetration, insufficient redox specificity, receptor redundancy, and a lack of well-designed human trials. This review summarizes current knowledge on HMGB1 biology, disease relevance, and therapeutic targeting, and highlights key challenges and future directions for HMGB1-based anti-inflammatory therapies in neuroinflammatory disorders.},
}

@article {pmid41964835,
year = {2026},
author = {Bekena, S and Singh, RK and Zhu, Y and Trani, JF and Ances, BM and Babulal, GM},
title = {Grip strength modifies the association between blood-based alzheimer's biomarkers and cognitive function.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41964835},
issn = {2509-2723},
support = {R01 AG074302/AG/NIA NIH HHS/United States ; R01 AG068183/AG/NIA NIH HHS/United States ; R01 AG067428/AG/NIA NIH HHS/United States ; U19AG073585-01/AG/NIA NIH HHS/United States ; },
abstract = {Blood-based biomarkers are increasingly used to characterize Alzheimer's disease (AD)-related pathology, yet substantial heterogeneity exists in how biomarker burden relates to cognitive performance. Grip strength, a marker of frailty and functional reserve, may modify this relationship. We conducted a cross-sectional analysis of 348 participants from the Aging Adult Brain Connectome (AABC) study. Global cognition was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma biomarkers included phosphorylated tau-217 (pTau217), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and total tau (tTau). Multiple linear regression models tested biomarker × grip strength interactions, adjusting for demographic factors, APOE ε4 status, cardiometabolic risk factors, body mass index, and creatinine. Sensitivity analyses included age-based propensity score matching and age-stratified models. Participants with low PACC were older, had lower grip strength, and higher plasma biomarker levels than those with normal cognition (all p < 0.001). In adjusted models, significant interactions between low grip strength and biomarkers were observed for pTau217 (β = - 0.046, p < 0.01), NfL (β = - 0.002, p < 0.001), and GFAP (β = - 0.005, p < 0.05). Age-matched showed attenuation of some interaction effects except for low grip strength and NfL. Age-stratified analyses showed a significant interaction for NfL among adults ≥ 65 years and for GFAP among those < 65 years. Grip strength moderated the association between plasma AD-related biomarkers and cognitive performance, supporting physical strength as an indicator of vulnerability. Integrating simple strength measures with blood biomarkers may improve cognitive risk stratification in community-dwelling adults.},
}

@article {pmid41964857,
year = {2026},
author = {Ramírez-Olvera, A and Almazán, JL and Pérez-Martínez, L and Pedraza-Alva, G},
title = {BDNF Protects Against Neuronal Damage Induced by TNF and β-Amyloid Peptides by Targeting JNK Activation.},
journal = {Neurochemical research},
volume = {51},
number = {2},
pages = {},
pmid = {41964857},
issn = {1573-6903},
support = {477677//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; 773657//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; IFC2016-2282//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; CF/2019-40792//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; IN217822//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; IN213119//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; },
}

@article {pmid41964873,
year = {2026},
author = {Hong, M and Lee, SER},
title = {Internal Structure and Reliability of the Public Stigma of Alzheimer's Disease Scale (PSAD-K) Among Korean Americans.},
journal = {Journal of cross-cultural gerontology},
volume = {41},
number = {2},
pages = {},
pmid = {41964873},
issn = {1573-0719},
}

@article {pmid41964934,
year = {2026},
author = {Ghosh, N and Pathak, S and Bera, R and Sharma, A and Kakkar, D and Kurmi, BD and Srivasatava, P and Ghosh, M and Karwasra, R and Ansori, ANM and Das, S and Sharma, N},
title = {Biomimetic nanocarriers as advanced drug delivery strategies in neurological disorders.},
journal = {Expert opinion on drug delivery},
volume = {},
number = {},
pages = {},
doi = {10.1080/17425247.2026.2659924},
pmid = {41964934},
issn = {1744-7593},
abstract = {INTRODUCTION: Neurological disorders represent a major and growing global health challenge due to complex central nervous system pathology and limited drug penetration across the blood - brain barrier. Conventional therapies are largely symptomatic and often fail to achieve sufficient brain bioavailability or disease modification. Biomimetic nanocarriers have emerged as a promising strategy to improve brain targeting and therapeutic efficacy.

AREAS COVERED: This review discusses recent advances in biomimetic nanocarriers for the treatment and diagnosis of neurological disorders. We summarize the pathological mechanisms underlying central nervous system diseases and discuss how cell membrane-coated nanocarriers derived from red blood cells, platelets, immune cells, stem cells, and cancer cells can enhance BBB penetration, immune evasion, and targeted delivery. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to evaluate therapeutic and diagnostic applications in Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, ischemic stroke, and glioblastoma.

EXPERT OPINION: Biomimetic nanocarriers offer a promising strategy to overcome biological barriers and improve central nervous system drug delivery. However, clinical translation remains challenged by membrane source standardization, scalability, and safety concerns. Future research should focus on reproducible manufacturing, regulatory frameworks, and long-term toxicity evaluation to accelerate clinical adoption.},
}

@article {pmid41964958,
year = {2026},
author = {Fukui, M and Kaise, T and Masaki, T and Sakamoto, T and Kageyama, R},
title = {Activation of neurogenesis improves amyloid-β pathology and cognitive function through AMP kinase signaling in Alzheimer's disease model mice.},
journal = {Cell reports},
volume = {45},
number = {4},
pages = {117250},
doi = {10.1016/j.celrep.2026.117250},
pmid = {41964958},
issn = {2211-1247},
abstract = {Adult hippocampal neurogenesis declines with aging and in neurological disorders, leading to cognitive impairment. We previously showed that inducing Plagl2 and antagonizing Dyrk1a (iPaD) rejuvenates aged neural stem cells (NSCs), enhancing neurogenesis and cognition in aged mice. Here, we found that NSC-specific iPaD treatment activates neurogenesis, reduces amyloid-β deposition, and improves cognition in Alzheimer's disease model mice. Transcriptomic analysis revealed widespread changes in gene expression in the hippocampus after iPaD treatment. The upregulated genes include those associated with astrocyte and microglial activation involved in amyloid-β clearance, while several genes upregulated in Alzheimer's disease are downregulated. Among the latter genes, knockdown of Prkag2 in the hippocampus most effectively enhances neurogenesis and reduces amyloid-β accumulation. Notably, both iPaD treatment and Prkag2 knockdown activate AMP-activated protein kinase signaling, upregulating genes involved in autophagy and cellular homeostasis. These results suggest that Prkag2 may represent a promising therapeutic target for neurodegenerative diseases, including Alzheimer's disease.},
}

@article {pmid41965189,
year = {2026},
author = {Gouvea, RG and Bezerra, ES and Amaral, LG and da Conceição, RA and Pauli, FP and Coutinho, MS and Amaral, AP and de Oliveira, PCO and da Silva, FC and Teles de Souza, AM and de Moraes, MC and Forezi, LDSM},
title = {Dual inhibition of AChE and BuChE by coumarin-benzothiazole hybrids: potent candidates unveiled through innovative screening and docking studies.},
journal = {Bioorganic chemistry},
volume = {176},
number = {},
pages = {109838},
doi = {10.1016/j.bioorg.2026.109838},
pmid = {41965189},
issn = {1090-2120},
abstract = {Alzheimer's disease (AD) is closely associated with cholinergic dysfunction, and dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a promising therapeutic strategy. However, current screening methods for cholinesterase inhibitors, particularly Ellman-based assays, are prone to spectral interferences and limited analytical specificity, which may compromise accurate identification and kinetic characterization of potent inhibitors. In addition, highly potent dual AChE/BuChE inhibitors with well-defined structure-activity relationships remain limited. To address these limitations, this study combines rational molecular design with the development of a selective chromatographic screening platform based on magnetic particle-immobilized enzymes and post-column derivatization, enabling improved analytical specificity and reliable quantification of enzymatic activity. In this work, a series of novel coumarin-benzothiazole hybrids were designed, synthesized, and evaluated as potential dual ChE inhibitors. The target compounds were obtained through a multistep synthetic strategy involving formation of coumarin-benzothiazole 10 (90% yield), O-alkylation (81-89% yield), and nucleophilic substitution with nitrogen heterocycles to afford hybrids 13a-p in yields ranging from 19 to 92%. The compounds were first screened using a newly developed semi-automated chromatographic platform, which combines magnetic particle-immobilized enzymes with post-column derivatization, overcoming limitations of conventional Ellman-based assays. Donepezil was used as a proof-of-concept reference inhibitor, confirming the accuracy of the method. The analytical method demonstrated excellent linearity (R[2] = 0.9983-0.9992), precision (CV ≤ 7.8%), and accuracy within accepted validation limits. Biological evaluation revealed highly potent inhibitors, particularly 13a and 13m, which exhibited IC50 values of 1.0 ± 0.1 nM and 0.6 ± 0.1 nM against AChE, respectively, compared with 64.9 ± 16.0 nM for donepezil. For BuChE, 13m showed an IC50 of 109.2 ± 14.7 nM, while 13a displayed 1212.5 ± 144.0 nM, both lower than donepezil (2202 ± 326 nM). Kinetic studies confirmed a competitive mechanism of inhibition, with Kᵢ values as low as 0.12 ± 0.02 nM for AChE and 47.76 ± 15.14 nM for BuChE (13m). Molecular docking studies supported these findings, demonstrating key interactions within the catalytic sites of both enzymes. Additionally, in silico evaluations indicated that these derivatives have favorable druglikeness. Together, the results highlight coumarin-benzothiazole derivatives as promising dual-target ChEIs and establish the developed analytical method as a versatile tool for the discovery and characterization of new anti-AD candidates.},
}

@article {pmid41965454,
year = {2026},
author = {Wagle, MM and Liu, C and Liu, Z and Wang, Y and Kellis, M and Patrick, E and Yang, P},
title = {Interpretable deep generative ensemble learning for single-cell omics with Hydra.},
journal = {Molecular systems biology},
volume = {},
number = {},
pages = {},
pmid = {41965454},
issn = {1744-4292},
support = {1173469//DHAC | National Health and Medical Research Council (NHMRC)/ ; },
abstract = {Single-cell omics enable the dissection of cellular heterogeneity, yet the high dimensionality, inherent noise, and sparsity present significant challenges. These challenges are amplified for rare cell populations, which are often difficult to annotate reliably but can be central to development and disease. As single-cell assays increasingly capture multiple molecular layers, the integrative analysis of such multimodal data further increases complexity. Here, we propose Hydra, a deep generative framework based on an ensemble of variational autoencoders for effective learning of unimodal and multimodal single-cell omics data. Hydra implements interpretable modules for capturing cell-type-specific molecular signatures. The ensemble of such interpretable modules enables reproducible feature selection and robust cell-type annotation, with particular effectiveness for rare populations. We benchmarked Hydra on a repertoire of 21 datasets, including unimodal and multimodal single-cell omics data. Our results demonstrate that Hydra offers comparable to superior performance to several state-of-the-art methods. Finally, we highlight the utility of Hydra in robustly annotating brain cellular subtypes and preserving disease-relevant signatures using our previously published dataset that profiles Alzheimer's disease.},
}

@article {pmid41965547,
year = {2026},
author = {Shi, Y and Fang, Z and Chen, Y and Lin, R and Huang, C and Li, H and Yan, Y},
title = {Prevalence and risk factors of loneliness in older adults with preclinical and prodromal Alzheimer's disease: the impact of depression, frailty-weight loss and quality of life.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07432-8},
pmid = {41965547},
issn = {1471-2318},
support = {2020Y9021//Innovation of Science and Technology of Fujian Province/ ; 2023J05224//Natural Science Foundation of Fujian Province/ ; },
}

@article {pmid41965602,
year = {2026},
author = {Meléndez, JC and Escudero, J and Satorres, E and Pitarque, A and Marti-Hoyos, I and Gonzalez-Moreno, J},
title = {Combined home-delivered transcranial direct current stimulation and cognitive training in older adults with mild cognitive impairment due to Alzheimer's disease: a randomized, single-blind, sham-controlled trial.},
journal = {BMC geriatrics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12877-026-07481-z},
pmid = {41965602},
issn = {1471-2318},
support = {PID2022-136798OB-I00//Ministerio de Ciencia e Innovación/ ; },
}

@article {pmid41965633,
year = {2026},
author = {Mansel, CO and Ghisays, V and Mahnken, JD and Swerdlow, RH and Reiman, EM and Karnes, JH and Denny, JC and Veatch, OJ},
title = {Downward bias in the association between APOE and Alzheimer's disease using prevalent and by-proxy disease sampling in the All of Us research program.},
journal = {BMC medical genomics},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12920-026-02362-1},
pmid = {41965633},
issn = {1755-8794},
support = {P30 AG072973/NH/NIH HHS/United States ; P30 AG072973/NH/NIH HHS/United States ; P30 AG035982/NH/NIH HHS/United States ; 1OT2OD026549/NH/NIH HHS/United States ; ZIA HG200417/NH/NIH HHS/United States ; P30 AG035982/NH/NIH HHS/United States ; },
}

@article {pmid41965638,
year = {2026},
author = {Khan, AJ and Rahman, I and Beg, HA and Akter, S and Haque, R and Monsur, DT and Rani, H and Dom, TNM},
title = {Association of periodontitis and tooth loss with cognitive decline in the older adults - a systematic review.},
journal = {BMC oral health},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12903-026-08310-w},
pmid = {41965638},
issn = {1472-6831},
abstract = {BACKGROUND: The increasing global burden of dementia highlights the importance of identifying factors that may contribute to cognitive decline in later life. Growing evidence suggests that chronic oral conditions, particularly periodontitis (PD) and tooth loss, may be associated with Alzheimer's disease (AD) and related dementias. This study synthesizes current observational evidence on the association between PD, tooth loss, and cognitive impairment (CI) among older adults.

METHODS: A comprehensive literature search was conducted in PubMed, the Cochrane Library, Embase, Scopus, and Google Scholar for English-language studies published between 2010 and 2025. Cross-sectional and longitudinal cohort studies examining associations between PD, tooth loss, and CI were included. Study selection, data extraction, and quality assessment were performed in accordance with PRISMA 2020 guidelines.

RESULTS: Thirteen studies met the inclusion criteria, with sample sizes ranging from 40 participants to over 500,000 individuals in large population-based cohorts. Most studies focused on adults aged ≥ 50 years, particularly those aged 60 years and above. Periodontal status, tooth loss, and cognitive outcomes were assessed using heterogeneous diagnostic methods. Most studies reported significant associations between PD or tooth loss and CI, dementia, or AD. Periodontal treatment appeared protective in several studies, although some associations weakened after adjustment for confounders.

CONCLUSIONS: The findings support PD and tooth loss are consistently associated with adverse cognitive outcomes, although causal relationships cannot be established due to methodological heterogeneity and residual confounding. Integrating oral health care into geriatric and dementia-prevention strategies may help preserve cognitive function and improve quality of life among older adults.},
}

@article {pmid41965687,
year = {2026},
author = {Hamed, FM and Mady, MS and Elgayed, SH and Mansour, YE and Mahgoub, S and Lai, KH and Lin, CY and Elsayed, HE and Moharram, FA},
title = {Carpoxylon macrospermum leaf extract and its phenolic compounds: a multi-targeted therapeutic remedy for Alzheimer's disease.},
journal = {BMC complementary medicine and therapies},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12906-026-05365-8},
pmid = {41965687},
issn = {2662-7671},
support = {MOST 111-2320-B-038-040-MY3, 113-2628-B-038-009-MY3, and 113-2321-B-255-001//National Science and Technology Council of Taiwan/ ; },
}

@article {pmid41965693,
year = {2026},
author = {Liu, J and Liu, J and Fan, Y and Liu, C and Cao, J and Ma, H and Hou, Y and Gao, S and Wang, P},
title = {Targeting the astrocyte-microglia EFEMP1-GALNT10 axis: a spatially programmable therapeutic strategy for hippocampal vulnerability in Alzheimer's disease.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08098-x},
pmid = {41965693},
issn = {1479-5876},
support = {82030064//The State Key Program of the National Natural Science Foundation of China grants/ ; L246009//Natural Science Foundation of Beijing Municipality/ ; },
}

@article {pmid41965838,
year = {2026},
author = {Yoo, JK and Kim, JH},
title = {Genome-wide investigation of synthetic rescue interactions in Alzheimer's disease implicates glial lipid and sterol metabolism.},
journal = {Alzheimer's research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13195-026-02009-4},
pmid = {41965838},
issn = {1758-9193},
support = {RS-2023-NR077290//National Research Foundation of Korea/ ; RS-2023-NR077290//National Research Foundation of Korea/ ; Education and Research Encouragement Fund//Seoul National University Hospital/ ; Education and Research Encouragement Fund//Seoul National University Hospital/ ; },
}

@article {pmid41965896,
year = {2026},
author = {Wang, J and Chen, L and Wang, Z and Chen, XY and Zhang, S and Ding, D and Zhou, Y and Rager-Aguiar, R and Lin, G and Zhang, H and Boda, VK and Ortyl, TC and Nelson, PT and Bezprozvanny, I and Zhou, FM and Du, J and Wu, Z and Li, W and Liao, FF},
title = {Pyrazole-derived TRPC3 antagonist ameliorates synaptic dysfunctions and memory deficits in Alzheimer's disease models.},
journal = {Molecular psychiatry},
volume = {},
number = {},
pages = {},
pmid = {41965896},
issn = {1476-5578},
abstract = {Transient receptor potential canonical (TRPC) channels are widely expressed in the brain; however, their precise roles in neurodegenerative diseases, such as Alzheimer's disease (AD), remain elusive. We found that TRPC3 expression is upregulated in excitatory neurons of brains with AD. We tested a selective inhibitor (JW-65) for TRPC3 over TRPC6 to investigate the potentially distinct role of TRPC3 in AD. JW-65 treatment significantly restored impaired synaptic plasticity and learning memory in acute and chronic experimental AD models. JW-65 treatment of late symptomatic 5XFAD transgenic mice reversed the impaired LTP, correlating with their significantly corrected synaptic gene expression based on hippocampal RNA-seq data analysis. JW-65 also provided synaptic protection in primary rat hippocampal neurons against soluble β-amyloid oligomers (AβOs), primarily via restoring the AβOs-impaired Ca[2+]/calmodulin-mediated signaling pathways. JW-65 treatment also significantly prevented Ca[2+] overload induced by AβOs. These findings suggest that aberrantly upregulated TRPC3, as a novel non-selective ion channel, significantly contributes to Ca[2+] dyshomeostasis in AD. Our work identifies TRPC3 as a potential therapeutic target for treating or preventing synaptic dysfunction of AD.},
}

@article {pmid41966037,
year = {2026},
author = {Qudoos, MA and Elliott, DP},
title = {Review of Donanemab and Lecanemab in Mild Dementia Stage of Alzheimer's Disease: Progress and Challenges.},
journal = {The Senior care pharmacist},
volume = {41},
number = {3},
pages = {98-108},
doi = {10.4140/TCP.n.2026.98},
pmid = {41966037},
issn = {2639-9636},
mesh = {Humans ; *Alzheimer Disease/drug therapy ; *Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects ; *Antibodies, Monoclonal/therapeutic use/adverse effects ; Amyloid beta-Peptides/metabolism ; },
abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and functional impairment, primarily driven by the accumulation of amyloid-beta (Aβ) plaques and tau tangles. Historically, treatments have focused on symptomatic relief; however, recent therapeutic advances have focused on disease-modifying monoclonal antibodies (mAbs), notably lecanemab and donanemab, which target Aβ pathology in early-stage AD. This review explores the clinical efficacy, safety profile, and limitations of lecanemab and donanemab, emphasizing key findings from the CLARITY-AD and TRAILBLAZER-ALZ 2 trials. In these studies, lecanemab was shown to slow cognitive decline by 27% over 18 months, while donanemab achieved a 28.9% reduction over 76 weeks, with the greatest benefits observed in patients presenting with lower baseline tau pathology.Despite these promising outcomes, challenges remain, including possible reduced efficacy in women based on subgroup analyses of trial data, racial disparities in trial representation, adverse effects such as amyloid-related imaging abnormalities (ARIA), and substantial cost and accessibility barriers. This review underscores the need for more inclusive research, personalized treatment strategies, and continued exploration of AD's complex pathology beyond amyloid clearance.},
}

Humans
*Alzheimer Disease/drug therapy
*Antibodies, Monoclonal, Humanized/therapeutic use/adverse effects
*Antibodies, Monoclonal/therapeutic use/adverse effects
Amyloid beta-Peptides/metabolism

@article {pmid41966233,
year = {2026},
author = {Rusinek, H and Bokacheva, L and Chen, H and Masurkar, A and Osorio, R and Betensky, R and Vedvyas, A and Chodosh, J and Shao, Y and Shepherd, T and Marsh, K and Wisniewski, T},
title = {Test-retest Reliability of FreeSurfer Measures of Neurodegeneration.},
journal = {NeuroImage},
volume = {},
number = {},
pages = {121920},
doi = {10.1016/j.neuroimage.2026.121920},
pmid = {41966233},
issn = {1095-9572},
abstract = {Reliable structural brain measurements are essential for studying neurodegeneration and for designing adequately powered aging and Alzheimer's disease (AD) research. We evaluated the test-retest reliability of FreeSurfer 7.1 morphometric measures in 100 older adults (mean age 73.5 years) ranging from cognitively unimpaired to dementia. Each participant underwent two T1-weighted 3T MRI scans on the same scanner within a short interval (mean 5.5 weeks), minimizing biological change. Segmentation was performed in both standard cross-sectional and longitudinal FreeSurfer modes, focusing on AD-relevant entorhinal cortex, hippocampus, lateral ventricles, choroid plexus, and the AD cortical thickness signature. Reliability was quantified using absolute and root-mean-square test-retest differences, standard deviation of differences, and intraclass correlation coefficients. Longitudinal processing improved precision by 15-50% across most measures compared with cross-sectional processing, with the largest gain observed for entorhinal thickness. Larger, anatomically well-defined regions (e.g., hippocampus, AD signature) demonstrated higher reliability than small structures or those with complex geometry (e.g., entorhinal cortex, choroid plexus). Image quality, indexed by the Euler characteristic, was the only factor significantly associated with measurement variability; reliability was unrelated to age, sex, cognitive status, inter-scan interval, or amyloid/tau PET burden. Power analyses indicated that detecting a 1% within-individual change requires sample sizes ranging from 36 (AD signature) to >300 (entorhinal cortex). We observed low reliability of choroid plexus volumetry by FreeSurfer 7. These results provide practical benchmarks for expected FreeSurfer measurement variability in older adults. They highlight the advantages of longitudinal processing and rigorous quality control for research on brain aging and AD.},
}

@article {pmid41966346,
year = {2026},
author = {Matuszewska, M and Cieślik, M and Sulejczak, D and Wilkaniec, A and Czapski, GA},
title = {BET protein inhibitor JQ1 reduces inflammationand hippocampal amyloid-β level without altering Tau phosphorylation in LPS-challenged adult wild-type mice.},
journal = {Brain research},
volume = {},
number = {},
pages = {150318},
doi = {10.1016/j.brainres.2026.150318},
pmid = {41966346},
issn = {1872-6240},
abstract = {A growing body of evidence highlights the role of infection and inflammation in the progression of Alzheimer's disease (AD). In this study, we aimed to analyze the impact of JQ1, an inhibitor of bromodomain and extraterminal domain (BET) proteins, which are key readers of the epigenetic acetylation code, on AD-related gene expression changes and biochemical alterations in the hippocampus during a lipopolysaccharide (LPS)-induced systemic inflammatory response in mice. JQ1 and LPS were administered intraperitoneally to adult male wild-type C57BL/6J mice. Changes in selected general and brain-specific parameters were measured for up to 12 h. Our results demonstrated that inhibition of BET proteins reduced LPS-induced sickness behavior and time-dependent elevation of proinflammatory signaling. LPS did not significantly alter amyloid-β (Aβ) levels; however, a significant reduction in Aβ load was observed in JQ1-treated animals overall, suggesting that BET proteins play a crucial role in regulating Aβ levels in the brain. At the same time, JQ1 treatment did not affect LPS-induced increases in phospho-Tau levels. Our results suggest that inhibiting BET proteins, in addition to their anti-inflammatory action, may be an effective strategy for reducing Aβ levels in the brain. However, a mechanistic explanation of this phenomenon requires further investigation.},
}

@article {pmid41966430,
year = {2026},
author = {Bertolli, A and Halhouli, O and Weber, MA and Liu-Martínez, Y and Wendt, LH and Blaine, B and Thangavel, R and Smadi, S and Pellatz, PJ and Liu, D and Bornhoft, KN and Gupta, K and Dean, R and Tish, MM and Kerr, G and Heiney, SA and Emmons, EB and Zhang, Q and Gumusoglu, SB and Narayanan, NS and Geerling, JC and Aldridge, GM},
title = {Renovating the Barnes maze for mouse models of dementia with STARR FIELD: A 4-day protocol for learning rate, retention, and cognitive flexibility.},
journal = {Methods (San Diego, Calif.)},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymeth.2026.04.004},
pmid = {41966430},
issn = {1095-9130},
abstract = {Land-based spatial mazes are a low-stress method to evaluate learning in rodent models of dementia. By using innate exploratory and hiding behavior, the Barnes maze requires fewer trials, allowing examination of early learning rate and retention, as well as executive and motivational features that can be characteristic of non-amnestic dementias. However, unwanted odor cues may disrupt interpretation of acquisition rate during typical learning trials. We designed and tested our Barnes FIELD protocol (Find the Invisible Exit to Locate the Domicile) to improve reproducibility, allow evaluation of learning trials, and limit experimenter influence. The protocol uses 3D-printed escape shuttles and docking tunnels, allowing mice to exit the maze to the home cage. We show evidence that our shuttles mitigate the possibility of undesired cues. We demonstrate the feasibility of our protocol across several models of cognitive impairment and aging, and develop an additional stage, the STARR (Spatial Training And Rapid Reversal) maze, to better challenge behavioral flexibility. By examining commonly used outcome measures we identify important considerations for interpretation. These insights are used to evaluate several models of cognitive change, including deficits in an Alzheimer's disease mouse model and behavioral flexibility in a model of brainstem dysfunction. This work provides comprehensive instructions to build, perform, and analyze a robust spatial maze that expands the range of behavioral and motivational outcomes that can be identified and screened. Our findings will aid interpretation of traditional protocols, enhance rigor and reproducibility, and provide an updated method to screen for cognitive changes in mice.},
}

@article {pmid41966598,
year = {2026},
author = {Gerards, M and Sannemann, L and Jessen, F},
title = {Structural social factors modify the association between Alzheimer's pathology and cognitive function.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {6},
pages = {100563},
doi = {10.1016/j.tjpad.2026.100563},
pmid = {41966598},
issn = {2426-0266},
abstract = {BACKGROUND: Social factors have been linked to cognitive decline and risk of dementia. However, our understanding of their impact on cognition in the context of Alzheimer's disease (AD) pathology is still limited.

OBJECTIVES: This study examined whether two structural social factors, relationship status (RS) and living situation (LS), modify the association between AD pathology and cognition.

DESIGN: Observational, analysis of existing cohort data.

SETTING: Data were obtained from the National Alzheimer's Coordinating Center (NACC) and the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study.

PARTICIPANTS: Participants with available data on cognitive performance, AD pathology, and structural social factors.

MEASUREMENTS: We used the Mini-Mental State Examination (MMSE), a widely used brief screening measure of global cognitive status. For the description of AD, postmortem neuropathology (NACC) reports, or amyloid PET (IDEAS) were used. RS and LS were coded according to the respective datasets. Group comparisons and regression models were used to evaluate interactions between RS or LS with AD pathology on cognition.

RESULTS: Across cohorts, up to 31% of individuals were not in a relationship, and up to 22% lived alone. Individuals in a relationship (RS+) or those who lived with someone (LS+) showed poorer cognitive performance than those not in a relationship (RS-) or living alone (LS-) at comparable levels of AD pathology. Interaction analyses indicated that the association between AD pathology and MMSE differed by LS, with LS+ being associated with slightly lower MMSE scores across pathology levels, an effect primarily driven by participants living with someone who is not a partner. In contrast, within the NACC cohort, RS+ individuals showed overall lower MMSE scores, while the association between AD pathology and MMSE was weaker compared to RS- individuals.

DISCUSSION: LS and RS showed differences in how AD pathology related to global cognitive status. Being in a relationship was linked to a weaker association between AD pathology and global cognitive status, whereas living with someone was associated with a lower global cognitive status at comparable levels of pathology. While the direction of these associations remains unclear, our findings suggest that the relationship between AD pathology and cognitive status may vary across different structural social contexts.},
}

@article {pmid41966601,
year = {2026},
author = {Zhao, Y and Luo, G and Huang, C and Chen, Z and Wei, Y and Chen, Q and Wang, F and Gan, Y and Yin, X},
title = {Comparative effects of some pharmacological and non-pharmacological interventions on cognitive function in Alzheimer's disease: A Bayesian network meta-analysis.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {6},
pages = {100564},
doi = {10.1016/j.tjpad.2026.100564},
pmid = {41966601},
issn = {2426-0266},
abstract = {BACKGROUND: Given the growing global public health burden of Alzheimer's disease, this study used the Bayesian network meta-analysis to assess the effects of pharmacological and non-pharmacological interventions on cognitive function in the population with Alzheimer's disease.

METHODS: Two investigators screened the literature from English databases (PubMed, MEDLINE, Embase, Cochrane CENTRAL, and Web of Science) and three major Chinese bibliographical databases (China National Knowledge Infrastructure Database, Wanfang Database, and VIP Database). We assessed the risk of bias and publication bias of the selected literature. Subsequently, a Bayesian network meta-analysis and meta-regression were conducted to further investigate the comparative efficacy of different interventions on cognitive outcomes.

RESULTS: A total of 4788 cases were initially identified. Photobiomodulation [SMD=0.66, 95%CrI (0.29, 1.02)], enriching environment [SMD=0.69, 95%CrI (0.08, 1.31)], pharmacological therapy [SMD=0.36, 95%CrI (0.17, 0.55)], cognitive stimulation therapy [SMD=0.32, 95%CrI (0.11, 0.55)] and exercise therapy [SMD=0.28, 95%CrI (0.06, 0.51)] showed considerable enhancements in cognitive function among individuals with Alzheimer's disease. Photobiomodulation and enriching environment stood out, with their effects more potent than those of other therapies, as indicated by the surface under the cumulative ranking curve - photobiomodulation clocked in at 87.3%, while enriching environment scored 83.8%, versus pharmacological therapy's 54.7%.

CONCLUSIONS: Among the interventions evaluated, photobiomodulation and enriching environment were associated with better improvements in cognitive function than pharmacological therapy. Exercise therapy and cognitive stimulation therapy also demonstrated beneficial effects. Music therapy showed no statistical difference from the control group. In addition, the research developed an innovative approach to contrast pharmacological and non-pharmacological treatments for Alzheimer's disease.

REGISTRATION: PROSPERO 2025 CRD420251075628. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251075628.},
}

@article {pmid41966622,
year = {2026},
author = {Cooper, G},
title = {It's time to address the recruitment bottleneck.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {5},
pages = {100571},
doi = {10.1016/j.tjpad.2026.100571},
pmid = {41966622},
issn = {2426-0266},
}

@article {pmid41966670,
year = {2026},
author = {Kaur, N and Gupta, S and Bansal, G and Bansal, Y},
title = {BACE-1 inhibitors as potential drug candidates for treatment of Alzheimer's disease: a systematic review.},
journal = {Molecular diversity},
volume = {},
number = {},
pages = {},
pmid = {41966670},
issn = {1573-501X},
}

@article {pmid41966687,
year = {2026},
author = {Hua, J and Sheng, Q and Xiao, S and Zhou, Y and Qi, J and Jin, S},
title = {PACells identifies phenotype-associated cell states from single-cell chromatin accessibility profiles.},
journal = {American journal of human genetics},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajhg.2026.03.012},
pmid = {41966687},
issn = {1537-6605},
abstract = {Identifying cell states that drive clinical phenotypes is crucial for dissecting regulatory landscapes, pathogenesis, and targeted therapies of disease in single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq). Here, we present PACells, a framework that links clinical phenotypes from bulk ATAC-seq data with individual cells from scATAC-seq data to identify critical cell states at single-cell resolution. PACells outperforms other methods in predicting cells and molecular signatures associated with disease and gene mutation. PACells discerns clinical cell states and regulatory elements relevant to Alzheimer disease (AD) and poor survival in glioblastoma. Further, PACells is extended to transcriptomics for melanoma datasets with immunotherapy outcomes.},
}

@article {pmid41966729,
year = {2026},
author = {Stinson, SE and Shadrin, AA and Rahman, Z and Rødevand, L and Broce, IJ and Selbæk, G and Stefansson, H and Haavik, J and Parker, N and Koch, E and Frei, O and O'Connell, KS and Smeland, OB and Djurovic, S and Dale, AM and van der Meer, D and Andreassen, OA},
title = {Distinct metabolic signatures of Alzheimer's and Parkinson's disease revealed through genetic overlap.},
journal = {EBioMedicine},
volume = {127},
number = {},
pages = {106254},
doi = {10.1016/j.ebiom.2026.106254},
pmid = {41966729},
issn = {2352-3964},
abstract = {BACKGROUND: Metabolic dysfunction is a major risk factor for neurodegeneration, yet the genetic architecture linking systemic metabolism to Alzheimer's disease (AD) and Parkinson's disease (PD) remains unclear.

METHODS: We integrated genome-wide association data for 249 circulating metabolites and proglucagon with summary statistics for AD, PD, and cardiometabolic traits. Genetic correlations, polygenic overlap, causal relationships, and shared genetic loci were quantified using linkage disequilibrium score regression, high-definition likelihood, bivariate mixture modelling, Mendelian randomisation, and conjunctional false discovery rate analyses, followed by functional and tissue-specific enrichment analyses.

FINDINGS: AD displayed a metabolic-genetic profile aligned with body mass index, type 2 diabetes, coronary artery disease, and stroke, whereas PD exhibited largely opposing patterns (Spearman's rs = -0.26). Mendelian randomization analyses supported causal effects of lipoprotein subclasses, glutamine, and proglucagon on AD risk, with opposite or null effects in PD. Shared loci between metabolites and AD were enriched for lipid metabolism and cholesterol transport, whereas PD-associated loci were enriched for mitochondrial function, vesicle trafficking, and stress-response signalling.

INTERPRETATION: AD and PD are shaped by fundamentally distinct metabolic-genetic architectures. Metabolically targeted interventions, particularly those modulating lipid, amino acid, and proglucagon pathways, may require disease-specific and genetically informed strategies for prevention and treatment of neurodegenerative diseases.

FUNDING: Novo Nordisk Foundation (NNF23OC0099658), Marie Skłodowska-Curie Actions (801133), the Research Council of Norway (334920, 351751, 296030, 324252, 324499, 326813), the National Institutes of Health (U24DA041123, R01AG076838, U24DA055330, OT2HL161847, 5R01MH124839-02), NordForsk (164218), South-Eastern Norway Regional Health Authority (2020060), and the European Union's Horizon 2020 (847776, 964874, 101057454).},
}

@article {pmid41966730,
year = {2026},
author = {Henjum, K and Neerland, BE and Blennow, K and Zetterberg, H and Pollmann, CT and Olsen, RB and Solberg, L and Myrstad, M and Ødegaard, OT and Karabeg, A and Gulestøl, A and Idland, AV and Watne, LO},
title = {Biomarkers of Alzheimer's disease pathophysiology and delirium.},
journal = {EBioMedicine},
volume = {127},
number = {},
pages = {106252},
doi = {10.1016/j.ebiom.2026.106252},
pmid = {41966730},
issn = {2352-3964},
abstract = {BACKGROUND: Alzheimer's disease (AD) is characterised by amyloid-beta (A) and tau (T) pathology, and neurodegeneration (N). AT(N) neuropathology precedes the symptomatic presentation of the disease. This asymptomatic phase may present vulnerability towards delirium, but studies are inconclusive. In this cross-sectional study of hip fracture patients, we aimed to explore the association between AD biomarkers for AT(N) neuropathology and delirium, with focus on patients without clinical dementia.

METHODS: The AT(N) biomarkers were analysed in cerebrospinal fluid (CSF) in hip fracture patients (n = 401). Pre-fracture dementia was defined by IQCODE ≥3.44 (n = 164). Delirium was diagnosed according to the DSM-5 criteria. The CSF concentrations of amyloid-beta1-42 (Aβ42), amyloid-beta1-40 (Aβ40), phosphorylated tau181 (p-tau) and total-tau (t-tau) were quantified by Lumipulse G assays (Fujirebo, Ghent, Belgium). The Aβ42/Aβ40 ratio (cutoff A+ <0.72), p-tau181 (T+ >50 pg/ml) and t-tau (N+ >409 pg/ml) were used to determine A, T and N status, respectively.

FINDINGS: Hip fracture patients with delirium had lower CSF Aβ42 concentrations and higher concentrations of CSF p-tau and CSF t-tau than those without delirium (student's t-test, all p-values <0.001). Brain Aβ-deposition, A+ was more common in patients with delirium (χ[2] p < 0.001). In patients without pre-fracture dementia, delirium was associated with lower CSF Aβ42 concentrations (student's t-test, p = 0.005), and higher CSF concentrations of p-tau (student's t-test p = 0.004) and t-tau (student's t-test p = 0.002). A higher proportion developed delirium among those A+T+ (33%) compared to A-T- (17%, χ[2] p = 0.02).

INTERPRETATION: These findings support that the AD AT neuropathology is a risk factor for delirium in patients without clinical dementia.

FUNDING: South-Eastern Norway Regional Health Authorities (# 2017095), the Norwegian Health Association (#16149, #19536, #1513) and by Wellcome Leap's Dynamic Resilience Program (jointly funded by Temasek Trust) (#104617).},
}

@article {pmid41966804,
year = {2026},
author = {Tejero, A and Benito-Patón, V and Griñán-Ferré, C and Pallás, M and León-Navarro, D and Martín, M},
title = {Resveratrol induces molecular changes in cholesterol homeostasis in SAMP8 mice cerebellum.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {198},
number = {},
pages = {119319},
doi = {10.1016/j.biopha.2026.119319},
pmid = {41966804},
issn = {1950-6007},
abstract = {Resveratrol (Rsv) is a natural polyphenol with neuroprotective properties that modulates several pathways implicated in Alzheimer's disease (AD). Cholesterol homeostasis is disrupted in AD patients, and this imbalance plays a key role in amyloid precursor protein (APP) processing, β-amyloid aggregation and membrane stability. The effect of Rsv on the cerebellum, an emerging structure in cognitive networks and AD pathology due to its high connectivity with other brain regions, remains largely unexplored. This study aims to characterize the effects of Rsv on the cerebellum of SAMP8 mice, an animal model of AD, at different ages (5- and 7-month-old mice) and to investigate how it act as a neuroprotective polyphenol in this structure via modulation of cholesterol metabolism. Aging caused a significant increase in cerebellar membrane free cholesterol levels, which were reversed by Rsv treatment. HMG-CoA reductase levels were significantly reduced by Rsv treatment in 5-month-old mice, suggesting that this polyphenol modulates cholesterol synthesis. Parameters related to cholesterol trafficking were also modulated, with increased LDL receptor levels, but without affecting ApoE. Mitochondrial electron transport chain complexes were also upregulated by Rsv treatment in 5-month-old animals, without affecting mitochondrial dynamics. Collectively, these data demonstrate-for the first time-that Rsv modulates key aspects of cholesterol metabolism and mitochondrial function in the cerebella of SAMP8 mice.},
}

@article {pmid41966869,
year = {2026},
author = {Iordan, AD and Pruitt, PJ and Ploutz-Snyder, R and Ghosh, B and Devignes, Q and Hampstead, BM},
title = {2 mA is NOT 2 mA: Electric field variability in high-definition tDCS and its implications for precision neuromodulation in aging.},
journal = {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology},
volume = {},
number = {},
pages = {2111877},
doi = {10.1016/j.clinph.2026.2111877},
pmid = {41966869},
issn = {1872-8952},
abstract = {OBJECTIVE: To evaluate intra- and inter-subject variability in electric field (EF) delivered by high-definition transcranial direct current stimulation (HD-tDCS) in neurologically mixed older adults, and test whether using multiple MRI sequences reduces variability.

METHODS: We used ROAST to simulate EF distributions for two HD-tDCS 4 × 1 montages in 442 adults (age 50-94) across the "normal" to dementia continuum. Individualized head models were built from structural MRI, using T1-weighted alone or T1T2 dual-contrast segmentation. Montages targeted left inferior frontal gyrus (IFG) or right superior parietal lobule (SPL). EF magnitude was extracted from anatomically defined grey matter regions (left IFG, right SPL).

RESULTS: EF magnitude varied by up to 400% across, and up to 35% within, individuals even after excluding segmentation and EF outliers. Left IFG consistently showed higher and more variable EF than the right SPL. Dual-contrast (T1T2) segmentation improved non-brain tissue delineation but EF variability persisted (up to 300%).

CONCLUSIONS: Consonant with prior findings, 2 mA is NOT 2 mA within or across individuals, as delivered EF depends strongly on targeted region(s) and individual brain morphology.

SIGNIFICANCE: These findings reinforce the need for individualized modeling, especially for older and clinical populations, and for moving beyond scalp-based to delivered dose at brain level.},
}

@article {pmid41967035,
year = {2026},
author = {Bracone, F and Di Castelnuovo, A and Costanzo, S and Gialluisi, A and Bonaccio, M and Persichillo, M and De Curtis, A and Magnacca, S and Panzera, T and Orlandi, S and Cherubini, A and Cerletti, C and Donati, MB and de Gaetano, G and Iacoviello, L},
title = {Frailty index predicts the risk of 17 health outcomes in distinct ways: prospective findings from the Moli-sani Study.},
journal = {Age and ageing},
volume = {55},
number = {4},
pages = {},
doi = {10.1093/ageing/afag091},
pmid = {41967035},
issn = {1468-2834},
support = {DM 1557 11.10.2022//Investment PE8 - Project Age-It: 'Ageing Well in an Ageing Society'/ ; //National Recovery and Resilience Plan/ ; //Next Generation EU/ ; //Italian Ministry of University and Research (MIUR, Rome, Italy)/ ; },
mesh = {Humans ; Male ; Female ; Aged ; *Frailty/diagnosis/mortality/epidemiology ; Middle Aged ; Italy/epidemiology ; Prospective Studies ; Risk Factors ; Risk Assessment ; Hospitalization ; *Frail Elderly ; *Geriatric Assessment/methods ; Aged, 80 and over ; Chronic Disease/epidemiology/mortality ; Adult ; Age Factors ; Time Factors ; Proportional Hazards Models ; },
abstract = {BACKGROUND: Frailty reflects systemic vulnerability and is a major public health concern in ageing. This study examined how frailty relates to risk of death, hospitalisation and major chronic diseases.

METHODS: We analysed data from 20 975 adults (≥35 years, 52% women) recruited in 2005-10 from the population-based Moli-sani Study (Italy) and followed for a median of 15 years. Frailty was assessed using a multidimensional 29-item frailty index (FI). Cox models accounting for competing risks estimated hazard ratios (HR) for 17 incident outcomes, adjusted for age, sex and common covariates, including social status indicators.

RESULTS: Frailty was associated with increased risk of several adverse outcomes. Per 1-SD increase in FI, the risk of type-2 diabetes and coronary heart disease rose by 82% (HR = 1.82; 95% confidence interval 1.73-1.92; 1541 events) and 33% (HR = 1.33; 1.23-1.44; 756). FI was also associated with an increased risk of Parkinson's disease (HR = 1.25; 1.05-1.47; 158) and non-Alzheimer dementia (HR = 1.31; 1.11-1.54; 150). Cancer associations varied by site. FI also predicted hospitalisations for any cause (HR = 1.31; 1.28-1.34; 11 193), and all-cause mortality (HR = 1.35; 1.30-1.40; 2631). Analyses comparing frail and prefrail with fit categories, excluding early events, and stratified by sex showed consistent results, with indications of somewhat stronger associations among individuals younger than 65 years in certain outcomes.

CONCLUSION: FI predicts a wide range of chronic diseases, especially cardiometabolic and neurodegenerative outcomes, and their negative consequences, including hospitalisation and mortality. These findings reinforce the importance of frailty assessment in preventive strategies, risk stratification and integrated surveillance in the general population.},
}

Humans
Male
Female
Aged
*Frailty/diagnosis/mortality/epidemiology
Middle Aged
Italy/epidemiology
Prospective Studies
Risk Factors
Risk Assessment
Hospitalization
*Frail Elderly
*Geriatric Assessment/methods
Aged, 80 and over
Chronic Disease/epidemiology/mortality
Adult
Age Factors
Time Factors
Proportional Hazards Models

@article {pmid41967036,
year = {2026},
author = {Sanchez-Martinez, J and Solis-Urra, P and Fernandez-Gamez, B and Fernández-Ortega, J and Sánchez-Aranda, L and Erickson, KI and Ortega, FB and Esteban-Cornejo, I},
title = {Effects of a 24-week resistance exercise program on Alzheimer's disease brain signatures in cognitively unimpaired older adults: a secondary analysis of the AGUEDA randomized controlled trial.},
journal = {Age and ageing},
volume = {55},
number = {4},
pages = {},
doi = {10.1093/ageing/afag086},
pmid = {41967036},
issn = {1468-2834},
support = {PID2022-137399OB-I00//MCIN/AEI/10.13039/501100011033 and FSE+/ ; FPU22/03052 and FPU21/06192//Spanish Ministry of Science, Innovation and Universities/ ; N°72,220,164//National Agency for Research and Development (ANID)/Scholarship Program/DOCTORADO BECAS CHILE/2022/ ; RYC2019-027287-I//MCIN/AEI/10.13039/501100011033/and 'ESF Investing in your future'/ ; RTI2018-095284-J-I00//MCIN/AEI/10.13039/501100011033/and 'ERDF A way of making Europe'/ ; PID2022-137399OB-I00//MCIN/AEI/10.13039/501100011033/and 'ERDF A way of making Europe'/ ; CNS2024-154835//MCIN/AEI/10.13039/501100011033/and 'ERDF A way of making Europe'/ ; },
mesh = {Humans ; Aged ; Female ; Male ; *Alzheimer Disease/diagnostic imaging/psychology/therapy/physiopathology ; *Resistance Training/methods ; *Cognition ; Single-Blind Method ; *Brain/diagnostic imaging/physiopathology ; Aged, 80 and over ; Treatment Outcome ; Time Factors ; Diffusion Magnetic Resonance Imaging ; Age Factors ; },
abstract = {BACKGROUND: Brain imaging markers may help detect early cognitive decline and Alzheimer's disease (AD). Although exercise-related effects on AD-specific brain signatures remain unclear.

OBJECTIVE: To examine the effects of a 24-week resistance exercise (RE) program on AD brain signatures in cognitively unimpaired older adults, to explore potential moderators and to assess associations with cognition, including mediation effects.

METHODS: This secondary analysis of a single-site, two-arm, single-blinded randomized controlled trial included 90 participants (72 ± 4 years; 58% female) randomly assigned by a blind external researcher to an RE group (3 sessions/week, 60 min/session, n = 46) or a wait-list control group (CG, n = 44). T1- and diffusion-weighted MRI were acquired at baseline and post-intervention. Primary outcomes were thickness/volume and grey matter mean diffusivity (GMMD) signatures, derived from cortical and hippocampal regions. Moderators included age, sex, education, multimorbidity, apolipoprotein E ϵ4 status, amyloid beta (Aβ) status and baseline AD brain signatures. Secondary outcomes included cognitive function. Outcome measures and analyses were conducted by staff blinded to intervention assignment.

RESULTS: Compared with the CG, the RE group showed a reduction in the thickness/volume signature (-0.23 standardized mean difference [SMD]; 95% CI, -0.43 to -0.02), but no effect on the GMMD signature (0.08 SMD; 95% CI, -0.13 to 0.29). Aβ-status moderated the effect, as Aβ-positive participants in the RE group showed a larger reduction in the thickness/volume signature than those in the CG (-0.64 SMD; 95% CI, -1.09 to -0.18), whereas no effect was observed in Aβ-negative participants. Thickness/volume and GMMD reductions were associated with improvements in executive function and attentional/inhibitory control, respectively. Changes in AD signatures did not mediate cognitive outcomes.

CONCLUSION: Our findings suggest that reductions in the macrostructural AD signature following a 24-week RE program may reflect adaptive, rather than detrimental, brain changes, particularly in Aβ-positive older adults, as these changes were associated with improved executive function.

TRIAL REGISTRATION: Registered on Clinicaltrials.gov (Identifier: NCT05186090).},
}

Humans
Aged
Female
Male
*Alzheimer Disease/diagnostic imaging/psychology/therapy/physiopathology
*Resistance Training/methods
*Cognition
Single-Blind Method
*Brain/diagnostic imaging/physiopathology
Aged, 80 and over
Treatment Outcome
Time Factors
Diffusion Magnetic Resonance Imaging
Age Factors

@article {pmid41967112,
year = {2026},
author = {Alam, MS and Kaddurah-Daouk, R and Luo, S},
title = {Joint modeling of high-dimensional longitudinal data and survival using supervised low-rank tensor decomposition.},
journal = {Biostatistics (Oxford, England)},
volume = {27},
number = {1},
pages = {},
doi = {10.1093/biostatistics/kxag007},
pmid = {41967112},
issn = {1468-4357},
support = {R01AG064803/AG/NIA NIH HHS/United States ; P30AG072958/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; Longitudinal Studies ; Alzheimer Disease/diagnostic imaging ; *Models, Statistical ; Monte Carlo Method ; Survival Analysis ; Computer Simulation ; Proportional Hazards Models ; Neuroimaging ; Biostatistics/methods ; Algorithms ; },
abstract = {High-dimensional longitudinal data are increasingly available in biomedical research, especially from omics platforms, but pose substantial challenges for joint modeling with survival outcomes. These challenges include modeling complex temporal dynamics, accommodating cross-feature dependencies, and maintaining computational feasibility. We propose a novel joint modeling framework that addresses these issues using supervised low-rank functional tensor decomposition to capture latent structure in multivariate longitudinal data and proportional hazards modeling for time-to-event outcomes. The longitudinal process is represented as a multivariate functional tensor, with a low-rank approximation that incorporates supervision from baseline covariates. Estimation is performed using a likelihood-based Monte Carlo Expectation-Maximization algorithm, enabling coherent inference and individualized prediction. Our method produces dynamic predictions of both longitudinal feature trajectories and survival probabilities. Simulation studies demonstrate substantial improvements in estimation accuracy and predictive performance over a standard two-stage approach, particularly under high censoring and limited sample sizes. In application to the Alzheimer's Disease Neuroimaging Initiative lipidomics data, the proposed model explains over 99% of variation with four components, and identifies significant subject-level latent predictors of dementia onset. This framework provides a scalable and interpretable strategy for integrating high-dimensional longitudinal biomarkers into joint models for disease progression and risk stratification.},
}

Humans
Longitudinal Studies
Alzheimer Disease/diagnostic imaging
*Models, Statistical
Monte Carlo Method
Survival Analysis
Computer Simulation
Proportional Hazards Models
Neuroimaging
Biostatistics/methods
Algorithms

@article {pmid41967208,
year = {2026},
author = {Guo, Y and Wang, N and Tao, Z and Huang, X and Yu, W and Zeng, J and Liu, X and Chen, S and Hua, F and Wang, X},
title = {The Ubiquitin-proteasome system in neuroinflammation and neurodegeneration: Molecular insights and therapeutic avenues.},
journal = {International immunopharmacology},
volume = {179},
number = {},
pages = {116599},
doi = {10.1016/j.intimp.2026.116599},
pmid = {41967208},
issn = {1878-1705},
abstract = {BACKGROUND: Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), represent a major and growing public health burden. Neuroinflammation is a critical driver of pathology in these disorders, and the ubiquitin-proteasome system (UPS) has emerged as a central regulator of inflammatory signaling within the nervous system. This review systematically examines the molecular interplay between the UPS and neuroinflammation in the progression of AD and PD.

MAIN BODY: We synthesize the core advances of the past decade in targeting the UPS to modulate neuroinflammation for therapeutic intervention. The UPS, primarily through the specific actions of E3 ubiquitin ligases and deubiquitinating enzymes, exerts precise control over key neuroinflammatory pathways, including NF-κB and the NLRP3 inflammasome, thereby critically shaping the functional states of microglia and astrocytes. In AD, UPS-targeted strategies have evolved beyond the clearance of Aβ and tau to include the reprogramming of microglial phenotype via nodes such as A20 and C/EBPβ. In PD, therapeutic focus has centered on augmenting PINK1/Parkin-dependent mitophagy and on suppressing specific pro-inflammatory factors like Peli1 and USP9X to disrupt pathogenic neuroinflammatory circuits.

CONCLUSIONS: This review provides a focused update on the mechanisms linking UPS dysfunction to neuroinflammation in AD and PD. It highlights the translational potential of targeting specific UPS components to modulate glial cell activation, with particular emphasis on the NF-κB and NLRP3 inflammasome axes as key regulatory hubs for future therapeutic development.},
}

@article {pmid41967284,
year = {2026},
author = {Kurihara, M and Ihara, R and Yoshii, G and Shimasaki, R and Hatano, K and Bannai, T and Suzuki, F and Ishibashi, K and Furuta, K and Satoh, K and Tokumaru, AM and Ishii, K and Iwata, A},
title = {ATNIVS biomarker heterogeneity in real-world patients receiving lecanemab.},
journal = {The journal of prevention of Alzheimer's disease},
volume = {13},
number = {6},
pages = {100567},
doi = {10.1016/j.tjpad.2026.100567},
pmid = {41967284},
issn = {2426-0266},
abstract = {BACKGROUND: While amyloid-β (Aβ) biomarker positivity is sufficient before initiating anti-Aβ antibody therapy, recent revised criteria also highlight the importance of other biomarkers (ATNIVS) to understand heterogeneity in AD.

We reviewed patients who attended our specialty clinic between December 2023 and October 2024. Some participated in tau PET study ([18]F-MK6240). MRI was assessed using Fazekas score. Remaining samples were analyzed for plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and CSF α-synuclein seed amplification assay (SAA).

RESULTS: During the period, 200 attended and 147 proceeded to screening. Lecanemab was started in 93 of 108 A+ patients; mean age 74.2 years, 73.1% female. While all tested started on lecanemab were positive on amyloid PET, 21% had only regional positivity with lower Aβ burden (centiloid 31.3 ± 17.5 vs 67.6 ± 20.2) and higher age (79.2 ± 5.1 vs 73.3 ± 8.9). While all tested had CSF Aβ42/40 values below the single cut-off 0.067 in Japan, three (8.6%) had values close to the cutoff (0.059-0.067), all of whom were male. Other biomarkers also widely varied from normal to fully abnormal; CSF pTau181 (40.5-168 pg/mL, cut-off 56.5), tau PET-based Braak stage (0-VI), NfL (10.0-103.3 pg/mL), GFAP (121.9-652.5 pg/mL), Fazekas score (0-3), and positive α-synuclein SAA (25-33%). Some associations were indicated including higher Fazekas scores in amyloid PET regional-positive group and higher plasma NfL in CSF Aβ42/40 0.059-0.067 group.

CONCLUSIONS: We identified substantial heterogeneity in ATNIVS biomarker profiles among patients receiving lecanemab in a real-world setting.},
}

@article {pmid41967651,
year = {2026},
author = {Balasubramanian, N and Gaudencio, G and Khan, KM and Biggerstaff, N and Marcinkiewcz, CA},
title = {Adolescent social isolation facilitates tau spread in raphe nuclei, linking depression and hyperalgesia in Alzheimer's disease.},
journal = {Neurobiology of disease},
volume = {},
number = {},
pages = {107393},
doi = {10.1016/j.nbd.2026.107393},
pmid = {41967651},
issn = {1095-953X},
abstract = {Tau pathology in brainstem serotonergic circuits drives early neuropsychiatric dysfunction in Alzheimer's disease (AD), yet mechanisms linking social stress exposures to depression and altered pain perception remain unclear. Here, we show that adolescent social isolation, a critical psychosocial exposome factor, facilitates tau propagation in the dorsal raphe nucleus (DRN) and downstream raphe nuclei, producing both neuropsychiatric and pain-related sequelae. Tau[P301L] was transduced into the DRN of 30-day-old socially isolated or group-housed C57BL/6 J mice using AAV, with controls receiving AAV-GFP. Four weeks post-transduction, anxiety, social behavior, and pain sensitivity were assessed. Behavior data revealed that adolescent isolation alone increased anxiety-like behavior, while social deficits were observed only in tau[P301L] mice and were further exacerbated by isolation. Moreover, hyperalgesia was observed only in isolated tau[P301L] mice. Histological analysis at 8 weeks revealed focal phosphorylated tau (p-tau) in the DRN and trans-synaptic spread to median raphe (MRN) and raphe magnus (RMg) serotonergic neurons, accompanied by reduced TPH2 and increased p-tau in downstream nuclei. Fluorescence in situ hybridization confirmed altered expression of Slc6a4 and Tgm2, a stress-responsive gene implicated in AD. These results indicate that DRN p-tau under adolescent isolation stress drives neuropsychiatric phenotypes, while p-tau spread to MRN and RMg disrupts serotonergic modulation of pain. This study provides the first evidence that adolescent stress promotes p-tau propagation within the raphe nuclei, linking early neuropsychiatric and pain-processing deficits to prodromal Alzheimer's disease and identifying a critical pathway through which psychosocial exposome risk converges with p-tau pathology to enable early intervention.},
}

@article {pmid41967873,
year = {2026},
author = {Emery, CEG and Love, S and Miners, JS},
title = {New perspectives on VEGF signalling in Alzheimer's disease.},
journal = {Brain pathology (Zurich, Switzerland)},
volume = {},
number = {},
pages = {e70100},
doi = {10.1111/bpa.70100},
pmid = {41967873},
issn = {1750-3639},
abstract = {Vascular endothelial growth factor (VEGF) signalling mediates pleiotropic effects within the brain, encompassing angiogenesis, neuronal survival, and immune signalling. There is growing interest in the role of VEGF signalling in the pathophysiology of Alzheimer's disease (AD). The generation of single-cell brain atlases and recent large multi-omic studies, including analysis of CSF and bloods alongside post-mortem brain tissue, have provided novel insights into the role of VEGF signalling in AD. Disruption of the VEGF-A/VEGFR2 signalling pathway, due in part to elevated soluble VEGFR1 expression may contribute to pathogenic angiogenesis, BBB leakiness, and neuronal loss in AD. Induction of VEGF-B/VEGFR1 signalling in microglia suggests that dysregulated VEGF-mediated immune cell signalling is a further influence on AD pathogenesis. A reduction in expression of the 'protective' VEGFR3 and co-receptors neuropilin 1 and 2 has also been recently linked to cognitive decline in AD. In large clinical studies, lower VEGF-A levels in CSF and serum, raised soluble VEGFR1in CSF and elevated PlGF in CSF and serum, are predictive of more rapid cognitive decline and accelerated Alzheimer's disease neuropathological change (ADNC). This review discusses findings from recent multi-omic studies of large clinical and neuropathological studies that prompt reconsideration of the nature of VEGF signalling in AD and shed light on some of the complexities and previous conflicts within the field.},
}