Abstract
INTRODUCTION: Alzheimer disease (AD) plasma biomarkers are noninvasive 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. METHODS: In 1,067 Amish individuals aged ≥ 65, we measured plasma Aβ and tau to assess their relationships with AD-related outcomes. RESULTS: Among Amish individuals with AD, plasma 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 APOE ε4 carriers (OR = 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). DISCUSSION: 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.