Wang Ping, Song Yeunjoo E, Lynn Audrey, Miskimen Kristy, Gulyayev Alex, Prough Michael B, Dorfsman Daniel A, Laux Renee A, Fuzzell Sarada L, Hochstetler Sherri D, Zaman Andrew F, Adams Larry D, Caywood Laura J, Clouse Jason E, Herington Sharlene D, Whitehead Patrice, Liu Yining, Moore Noel, Ogrocki Paula, Lerner Alan J, Griswold Anthony J, Vance Jeffery M, Cuccaro Michael L, Scott William K, Pericak-Vance Margaret A, Haines Jonathan L
Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Cleveland Institute for Computational Biology, Cleveland, Ohio, USA.
Alzheimers Dement. 2025 Jun;21(6):e70328. doi: 10.1002/alz.70328.
Alzheimer's disease (AD) plasma biomarkers are non-invasive measures of the key amyloid beta (Aβ) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population.
In 1067 Amish individuals aged ≥ 65, we measured plasma Aβ and tau to assess their relationships with AD-related outcomes.
Among Amish individuals with AD, plasma phosphorylated tau protein at epitope 181 (p-tau181) was significantly higher (p = 0.04), and plasma Aβ42/p-tau181 ratio was significantly lower (p = 0.01) than cognitively normal individuals. The association of AD with elevated p-tau181 was driven by apolipoprotein E (APOE) ε4 carriers (odds ratio = 6.02, p < 0.001). Cluster analysis identified two subgroups defined by differing Aβ and tau levels, with the high-risk cluster having more APOE ε4 carriers (p < 0.001).
Plasma biomarkers, particularly p-tau181, Aβ42/Aβ40, and Aβ42/p-tau181 ratio, are promising surrogate biomarkers for AD-related pathology and clinical outcomes in the Amish.
阿尔茨海默病（AD）血浆生物标志物是关键淀粉样蛋白β（Aβ）和tau病理的非侵入性测量指标。需要进行验证和推广研究，以充分了解它们在老年人群中预测和诊断AD的潜力。
在1067名年龄≥65岁的阿米什人中，我们测量了血浆Aβ和tau，以评估它们与AD相关结局的关系。
在患有AD的阿米什人中，表位181处的血浆磷酸化tau蛋白（p-tau181）显著更高（p = 0.04），且血浆Aβ42/p-tau181比值显著更低（p = 0.01），与认知正常个体相比。AD与p-tau181升高的关联由载脂蛋白E（APOE）ε4携带者驱动（比值比 = 6.02，p < 0.001）。聚类分析确定了由不同Aβ和tau水平定义的两个亚组，高风险亚组有更多APOE ε4携带者（p < 0.001）。
血浆生物标志物，特别是p-tau181、Aβ42/Aβ40和Aβ42/p-tau181比值，是阿米什人中AD相关病理和临床结局有前景的替代生物标志物。
