1. Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid.
- Author
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Wojtas AM, Dammer EB, Guo Q, Ping L, Shantaraman A, Duong DM, Yin L, Fox EJ, Seifar F, Lee EB, Johnson ECB, Lah JJ, Levey AI, Levites Y, Rangaraju S, Golde TE, and Seyfried NT
- Subjects
- Humans, Male, Aged, Female, Brain metabolism, Tauopathies cerebrospinal fluid, Tauopathies blood, Supranuclear Palsy, Progressive cerebrospinal fluid, Supranuclear Palsy, Progressive blood, Cerebral Amyloid Angiopathy cerebrospinal fluid, Cerebral Amyloid Angiopathy genetics, Middle Aged, Aged, 80 and over, tau Proteins cerebrospinal fluid, Biomarkers cerebrospinal fluid, Biomarkers blood, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease blood, Alzheimer Disease genetics, Proteomics
- Abstract
Introduction: Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types., Methods: We conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control (N = 28), progressive supranuclear palsy (PSP) (N = 18), and AD (N = 21) cases., Results: Protein co-expression network analysis identified unique cerebrovascular modules significantly correlated with amyloid plaques, cerebrovascular amyloid angiopathy (CAA), and/or tau pathology. The protein products within AD genetic risk loci were concentrated within cerebrovascular modules. The overlap between differentially abundant proteins in AD cerebrospinal fluid (CSF) and plasma with cerebrovascular network highlighted a significant increase of matrisome proteins, SMOC1 and SMOC2, in CSF, plasma, and brain., Discussion: These findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
- Published
- 2024
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