INTRODUCTIONAlzheimer'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.METHODSTwo 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.RESULTSWhile 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.DISCUSSIONOur 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.Highlights 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.

中文翻译：

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跨种族和民族的阿尔茨海默病大脑区域的大规模深度蛋白质组学分析


引言阿尔茨海默病 （AD） 是最普遍的神经退行性疾病，但我们的理解主要依赖于对非西班牙裔白人 （NHW） 人群的研究。在这里，我们对不同种族/族裔群体的 AD 蛋白质组学景观进行了广泛的调查。方法来自多个中心的两个皮质区域通过统一的神经病理学诊断进行协调。在 998 名独立捐献者中，273 名捐献者自我认定为非裔美国人，229 名拉丁裔美国人，434 名捐献者为 NHW。结果淀粉样蛋白前体蛋白和微管相关蛋白 tau 在 AD 大脑中表现出较高的丰度，未观察到显着的种族相关差异。进一步的蛋白质组范围和重点分析 （特异性淀粉样蛋白 β [Aβ] 物种和 tau 结构域）支持大脑蛋白质组内这些 AD 病理不存在种族差异。讨论我们的研究结果表明，AD 风险和临床表现的种族差异并没有得到大脑蛋白质组显着差异模式的支持，这表明其他决定因素解释了这些临床差异。亮点 我们在 AD 病例中提出了 DLPFC （998） 和 STG （244） 的大规模蛋白质组 （∼10,000 个蛋白质）。大约 50% 的样本来自不同种族和民族的大脑捐献者。关键 AD 蛋白 （淀粉样蛋白和 tau） 与 CERAD 和 Braak 分期相关。在 AD 大脑中未观察到淀粉样蛋白和 tau 蛋白水平的显着种族相关差异。AD 相关蛋白质变化显示非裔美国人和白人个体的大脑蛋白质组之间具有很强的相关性。该数据集促进了对种族特异性 AD 通路和潜在疗法的理解。