Heritability of Alzheimer-related plasma biomarkers in the Amish population

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSPlasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored. METHODSWe measured plasma amyloid beta 40 (A{beta}40), A{beta}42, A{beta}42/A{beta}40, total tau (t-tau), phosphorylated tau 181 (p-tau181), A{beta}42/t-tau, A{beta}42/p-tau181, neurofilament light chain, and glial fibrillary acidic protein in the Midwestern Amish. Pedigree-based heritability [Formula] was estimated from multigenerational pedigrees, and SNP-based heritability [Formula] was derived from single nucleotide polymorphisms (SNPs). RESULTSAmong all Amish individuals, additive genetic effects [Formula] explained 11.1% to 36.6% of biomarker variances. [Formula] estimates were consistently lower, ranging from 6.7% to 28.7%. The heritability of these biomarkers in subgroups of cognitively normal individuals and APOE {varepsilon}4 non-carriers yielded similar results. DISCUSSIONPlasma biomarkers such as amyloid {beta}, t-tau, and p-tau181 are moderately heritable in the Amish, underscoring the impact of genetic determinants of plasma biomarkers associated with AD.