Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain

• Type of Material: Article
• Authors: Aliza Wingo, Emory University; Wen Fan, Emory University; Duc M. Duong, Emory University; Ekaterina S. Gerasimov, Emory University; Eric Dammer, Emory University; Yue Lu, Emory University; Nadia V. Harerimana, Emory University; Bartholomew White, Johns Hopkins University; Madhav Thambisetty, National Institutes of Health; Juan C. Troncoso, Johns Hopkins University; Namhee Kim, Rush University; Julie A. Schneider, Rush University; Ihab Hajjar, Emory University; James Lah, Emory University; David A. Bennett, Rush University; Nicholas Seyfried, Emory University; Allan Levey, Emory University; Thomas Wingo, Emory University
• Language: English
• Date: 2020-06-01
• Publisher: Nature Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41593-020-0635-5
• Title of Journal or Parent Work: NATURE NEUROSCIENCE
• Volume: 23
• Issue: 6
• Start Page: 696
• End Page: 700
• Grant/Funding Information: Support was provided by R01 AG056533, R01 AG053960, the Accelerating Medicine Partnership for AD (U01 AG046152; U01 AG046161; U01 AG061356; U01 AG061357), the Emory Alzheimer’s Disease Research Center (P50 AG025688), and the NINDS Emory Neuroscience Core (P30 NS055077), R01 AG017917 (DAB), R01 AG015819 (DAB), RC2 AG036547 (DAB), P30 AG10161 (DAB), R01 AG042210 (JAS), and in part by the intramural program of the National Institute on Aging. APW is also supported by U01 MH115484 and I01 BX003853. TSW is also supported by RF1 AG057470, R56 AG062256, R56 AG060757, and R56 AG062633. NTS is also supported by an Alzheimer’s Association, Alzheimer’s Research UK, The Michael J. Fox Foundation for Parkinson’s Research, the Weston Brain Institute Biomarkers Across Neurodegenerative Diseases Grant (11060), R01 AG061800, and R01 AG057911.
• Research Categories: Biology, Neuroscience; Psychology, Cognitive

Abstract

Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and RNA splicing and increased oligodendrocyte development and myelination. Consistently, single-cell RNA sequencing showed cerebral atherosclerosis associated with higher oligodendrocyte abundance. A subset of proteins and modules associated with cerebral atherosclerosis was also associated with Alzheimer’s disease, suggesting shared mechanisms.