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Updated: May 21, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Alzheimer's disease plasma biomarkers in the Midwestern Amish
Ping Wang1, Yeunjoo E Song1, Audrey Lynn1,2
1Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Introduction:
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.
Methods:
In 1067 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 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).
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.
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