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.
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This post is Copyright: Aleksandra M. Wojtas,
Eric B. Dammer,
Qi Guo,
Lingyan Ping,
Ananth Shantaraman,
Duc M. Duong,
Luming Yin,
Edward J. Fox,
Fatemeh Seifar,
Edward B. Lee,
Erik C. B. Johnson,
James J. Lah,
Allan I. Levey,
Yona Levites,
Srikant Rangaraju,
Todd E. Golde,
Nicholas T. Seyfried | May 8, 2024