Heritability of Alzheimer-related plasma biomarkers in the Amish population

Plasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored.

We measured plasma amyloid beta 40 (Aβ40), 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 $\left(h_{\text{ped}}^2\right)$ was estimated from multigenerational pedigrees, and SNP-based heritability ${(h}_{SNP}^2)$ was derived from single nucleotide polymorphisms (SNPs).

Among all Amish individuals, additive genetic effects $\left(h_{\text{ped}}^2\right)$ explained 11.1% to 36.6% of biomarker variances. $h_{SNP}^2$ estimates were consistently lower, ranging from 6.7% to 28.7%. The heritability of these biomarkers in subgroups of cognitively normal individuals and APOE ε4 non-carriers yielded similar results.

Plasma biomarkers such as amyloid β, t-tau, and p-tau181 are moderately heritable in the Amish, underscoring the impact of genetic determinants of plasma biomarkers associated with AD.