Heritability of Alzheimer-related plasma biomarkers in the Amish population
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INTRODUCTION
Plasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored.
METHODS
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 was estimated from multigenerational pedigrees, and SNP-based heritability was derived from single nucleotide polymorphisms (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 APOE ε4 non-carriers yielded similar results.
DISCUSSION
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.
