Affiliation:
1. Department of Biochemistry Emory University School of Medicine Atlanta Georgia USA
2. Center for Neurodegenerative Disease Emory University School of Medicine Atlanta Georgia USA
3. Department of Pathology and Laboratory Medicine University of Pennsylvania Pennsylvania USA
4. Department of Neurology Emory University School of Medicine Atlanta Georgia USA
5. Department of Pharmacology and Chemical Biology Emory University School of Medicine Atlanta Georgia USA
Abstract
AbstractINTRODUCTIONCerebrovascular 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.METHODSWe 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.RESULTSProtein 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.DISCUSSIONThese findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases.
Funder
National Institutes of Health
Alzheimer's Association