Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid.

Publisher: John Wiley & Sons, Ltd Country of Publication: United States NLM ID: 101231978 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-5279 (Electronic) Linking ISSN: 15525260 NLM ISO Abbreviation: Alzheimers Dement Subsets: MEDLINE

Publication: 2020- : Hoboken, NJ : John Wiley & Sons, Ltd.
Original Publication: Orlando, FL : Elsevier, Inc.

Biomarkers*/cerebrospinal fluid ; Biomarkers*/blood ; Alzheimer Disease*/cerebrospinal fluid ; Alzheimer Disease*/blood ; Alzheimer Disease*/genetics ; Proteomics*; 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

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.)

Update of: medRxiv. 2024 Jan 11:2024.01.10.24301099. doi: 10.1101/2024.01.10.24301099. (PMID: 38260316)

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F32 AG081135 United States AG NIA NIH HHS; RF1 AG062181 United States AG NIA NIH HHS; P30 AG066511 United States AG NIA NIH HHS; F32AG081135 United States NH NIH HHS; P30AG066511 United States NH NIH HHS; U01 AG061357 United States AG NIA NIH HHS; ABA-22-974673 United States ALZ Alzheimer's Association; R01 AG071587 United States AG NIA NIH HHS; U01AG061357 United States NH NIH HHS; RF1AG062181 United States NH NIH HHS

Keywords: Alzheimer's disease; amyloid; biomarkers; cerebral amyloid angiopathy; cerebrovasculature; mass spectrometry; progressive supranuclear palsy; tandem mass tag labeling; tau

0 (Biomarkers)
0 (tau Proteins)

Date Created: 20240507 Date Completed: 20240617 Latest Revision: 20240716

20240717

PMC11180878

10.1002/alz.13821

38713744