Large‐scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity

• DOI: 10.1002/alz.14360
• Publication Date: 2024-11-13T12:37:45Z
• Authors: Fatemeh Seifar; Edward J. Fox; Anantharaman Shan...; Yue Liu; Eric B. Dammer; Erica Modeste; Duc M. Duong; Luming Yin; Adam N. Trautwig; Qi Guo; Kaiming Xu; Lingyan Ping; Joseph S. Reddy; Mariet Allen; Zachary Quicksall; Laura Heath; Jo Scanlan; Erming Wang; Minghui Wang; Abby Vander Linden; William Poehlman; Xianfeng Chen; Saurabh Baheti; Charlotte Ho; Thuy Nguyen; Geovanna Yepez; Adriana O. Mitchell; Stephanie R. Oatman; Xue Wang; Minerva M. Carras...; Alexi Runnels; Thomas Beach; Geidy E. Serrano; Dennis W. Dickson; Edward B. Lee; Todd E. Golde; Stefan Prokop; Lisa L. Barnes; Bin Zhang; Varham Haroutunian; Marla Gearing; James. J Lah; Philip De Jager; David A Bennett; Anna Greenwood; Nilüfer Ertekin‐T...; Allan I. Levey; Aliza Wingo; Thomas Wingo; Nicholas T. Seyfried
• Keywords: Proteome

Abstract INTRODUCTION Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non‐Hispanic White (NHW) populations. Here we provide an extensive survey of proteomic landscape AD across diverse racial/ethnic groups. METHODS Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among 998 unique donors, 273 donors self‐identified as African American, 229 Latino and 434 NHW. RESULTS While amyloid precursor protein microtubule‐associated tau demonstrated higher abundance in brains, no significant race‐related differences observed. Further proteome‐wide focused analyses (specific beta [Aβ] species domains) supported absence racial these pathologies brain proteome. DISCUSSION Our findings indicate that risk clinical presentation are not underpinned dramatically divergent patterns proteome, suggesting other determinants account for disparities. Highlights We present a large‐scale proteome (∼10,000 proteins) DLPFC (998) STG (244) cases. About 50% samples racially ethnically donors. Key proteins (amyloid tau) correlated with CERAD Braak stages. No levels observed brains. AD‐associated changes showed strong correlation between proteomes American individuals. This dataset advances understanding ethnoracial‐specific pathways potential therapies.