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

• Published in: Alzheimer's & dementia 2024-11
• Main Authors: Seifar, Fatemeh, Fox, Edward J, Shantaraman, Anantharaman, Liu, Yue, Dammer, Eric B, Modeste, Erica, Duong, Duc M, Yin, Luming, Trautwig, Adam N, Guo, Qi, Xu, Kaiming, Ping, Lingyan, Reddy, Joseph S, Allen, Mariet, Quicksall, Zachary, Heath, Laura, Scanlan, Jo, Wang, Erming, Wang, Minghui, Linden, Abby Vander, Poehlman, William, Chen, Xianfeng, Baheti, Saurabh, Ho, Charlotte, Nguyen, Thuy, Yepez, Geovanna, Mitchell, Adriana O, Oatman, Stephanie R, Wang, Xue, Carrasquillo, Minerva M, Runnels, Alexi, Beach, Thomas, Serrano, Geidy E, Dickson, Dennis W, Lee, Edward B, Golde, Todd E, Prokop, Stefan, Barnes, Lisa L, Zhang, Bin, Haroutunian, Varham, Gearing, Marla, Lah, James J, De Jager, Philip, Bennett, David A, Greenwood, Anna, Ertekin-Taner, Nilüfer, Levey, Allan I, Wingo, Aliza, Wingo, Thomas, Seyfried, Nicholas T
• Format: Article
• Language: English
• ISSN: 1552-5260; 1552-5279; 1552-5279
• DOI: 10.1002/alz.14360

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