Heritability of Alzheimer's disease–related plasma biomarkers in the Amish population

Abstract INTRODUCTION Plasma biomarkers for Alzheimer's disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain under explored. METHODS We measured plasma amyloid beta (Aβ)40, Aβ42, Aβ42/Aβ40, total tau (t‐tau), phosphorylated tau 181 (p‐tau181), Aβ42/t‐tau, Aβ42/p‐tau181, neurofilament light chain, and glial fibrillary acidic protein in the Midwestern Amish. Pedigree‐based heritability () was estimated from multigenerational pedigrees, and single nucleotide polymorphism (SNP)–based heritability () was derived from SNPs. RESULTS Among all Amish individuals, additive genetic effects explained 11.1% to 36.6% of biomarker variances. estimates were consistently lower, ranging from 6.7% to 28.7%. The heritability of these biomarkers in subgroups of cognitively normal individuals and apolipoprotein E ε4 non‐carriers yielded similar results. DISCUSSION Plasma biomarkers such as Aβ, t‐tau, and p‐tau181 are moderately heritable in the Amish, underscoring the impact of genetic determinants of plasma biomarkers associated with AD.