Alzheimer Disease Plasma Biomarkers in the Mid-Western Amish

INTRODUCTIONAlzheimer disease (AD) plasma biomarkers are noninvasive measures of the key amyloid beta (A{beta}) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population. METHODSIn 1,067 Amish individuals aged [&ge;] 65, we measured plasma A{beta} and tau to assess their relationships with AD-related outcomes. RESULTSAmong Amish individuals with AD, plasma p-tau181 was significantly higher (p = 0.04), and plasma A{beta}42/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 {varepsilon}4 carriers (OR = 6.02, p < 0.001). Cluster analysis identified two subgroups defined by differing A{beta} and tau levels, with the high-risk cluster having more APOE {varepsilon}4 carriers (p < 0.001). DISCUSSIONPlasma biomarkers, particularly p-tau181, A{beta}42/A{beta}40, and A{beta}42/p- tau181 ratio, are promising surrogate biomarkers for AD-related pathology and clinical outcomes in the Amish.