INTRODUCTIONCerebrovascular 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.METHODSWe 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.RESULTSProtein 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.DISCUSSIONThese findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases.

中文翻译：

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阿尔茨海默病和相关 tau蛋白病中人类脑血管的蛋白质组变化与血浆和脑脊液中的外周生物标志物相关

简介 脑血管功能障碍是阿尔茨海默病（AD）的病理标志。然而，检测大量组织内的脑血管变化限制了我们表征不太丰富的细胞类型的蛋白质组学改变的能力。方法我们对来自同一个体的大量脑组织和分离的脑血管系统进行了定量蛋白质组学，包括对照（氮= 28), 进行性核上性麻痹 (PSP) (氮= 18), 和 AD (氮= 21) 例。 结果蛋白质共表达网络分析确定了与淀粉样蛋白斑、脑血管淀粉样血管病 (CAA) 和/或 tau 病理学显着相关的独特脑血管模块。 AD遗传风险位点内的蛋白质产物集中在脑血管模块内。 AD 脑脊液 (CSF) 和血浆中差异丰富的蛋白质与脑血管网络之间的重叠突出显示了脑脊液、血浆和大脑中基质体蛋白 SMOC1 和 SMOC2 的显着增加。讨论这些发现增强了我们对 AD 中脑血管缺陷、脱落的理解。揭示与神经退行性疾病中 CAA 和血管功能障碍相关的潜在生物标志物。