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Alzheimer's disease (AD) is driven by complex interactions between vascular dysfunction, glymphatic system impairment, and neuroinflammation. Vascular aging, characterized by arterial stiffness and reduced cerebral blood flow (CBF), disrupts the pulsatile forces necessary for glymphatic clearance, exacerbating amyloid-beta (Aβ) accumulation and cognitive decline. This review synthesizes insights into the mechanistic crosstalk between these systems and explores their contributions to AD pathogenesis. Emerging machine learning (ML) tools, such as DeepLabCut and Motion sequencing (MoSeq), offer innovative solutions for analyzing multimodal data and enhancing diagnostic precision. Integrating ML with imaging and behavioral analyses bridges gaps in understanding vascular-glymphatic dysfunction. Future research must prioritize these interactions to develop early diagnostics and targeted interventions, advancing our understanding of neurovascular health in AD.
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http://dx.doi.org/10.1016/j.nbd.2025.106877 | DOI Listing |
Mov Disord Clin Pract
September 2025
Department of Neurology, Danish Dementia Research Centre, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Background: Early identification of pathological α-synuclein deposition (αSynD) may improve understanding of Lewy body disorder (LBD) progression and enable timely disease-modifying treatments.
Objectives: We investigated αSynD using a seed amplification assay and assessed prodromal LBD symptoms in individuals with idiopathic olfactory dysfunction (iOD).
Methods: In this cross-sectional, case-control study, we included iOD participants and normosmic healthy controls (HC) aged 55 to 75 years without diagnoses of dementia with Lewy bodies, Parkinson's disease (PD), or other major neurological disorders.
Crit Rev Anal Chem
September 2025
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, India.
Neurodegenerative disorders (NDD) i.e., dementia of the Alzheimer's type, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are a rising worldwide epidemic driven by aging populations and characterized by progressive neuronal impairment.
View Article and Find Full Text PDFJ Neurochem
September 2025
Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Elucidating the earliest biological mechanisms underlying Alzheimer's disease (AD) is critical for advancing early detection strategies. While amyloid-β (Aβ) and tau pathologies have been central to preclinical AD research, the roles of peripheral biological processes in disease initiation remain underexplored. We investigated patterns of F-MK6240 tau positron emission tomography (PET) and peripheral inflammation across stages defined by Aβ burden and neuronal injury in n = 132 (64.
View Article and Find Full Text PDFACS Chem Neurosci
September 2025
Institute of Cell Engineering, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21215, United States.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuronal loss, with pathological hallmarks including Aβ plaque deposition and tau tangles. At present, the early diagnosis and treatment of AD still face great challenges, such as limited diagnostic methods, difficulty in blood-brain barrier (BBB) penetration, complex disease mechanisms, and lack of highly effective targeted therapies. Antibody drugs have shown broad prospects in the field of AD due to their high specificity, engineering and multifunctional therapeutic potential, include targeted Aβ clearance, tau pathological regulation, imaging probes, and blood biomarkers.
View Article and Find Full Text PDFCurr Alzheimer Res
September 2025
School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University, 47500 Subang Jaya, Selangor, Malaysia.
Introduction: Alzheimer's disease is expressed as chronic neuroinflammation in the brain, which results in neuronal dysfunction, aberrant protein folding, and declining cognitive abilities. miR-146a-5p is a potent anti-inflammatory agent that can be used to treat several inflammatory diseases, as well as promote wound healing. Our research aimed to utilize network pharmacology to elucidate the therapeutic potential of miR-146a-5p in treating Alzheimer's disease using a biocomputational approach.
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