Heritability of Alzheimer's disease plasma biomarkers: A nuclear twin family design

Abstract

INTRODUCTIONAlzheimer's disease (AD) is a highly heritable disease (60%–80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers.METHODSBlood concentrations of Aβ42/40, NfL, and GFAP of twins and their families (monozygotic twins: 1574, dizygotic twins: 1266, other: 3657) were analyzed on the Simoa HD‐X. Twin‐family models were used to estimate proportional genetic contributions to the variance in biomarker levels.RESULTSHeritability estimates were 16% for Aβ42/40, 42% for NfL, and 60% for GFAP. NfL and GFAP were significantly correlated with each other (0.37) but not with Aβ42/40.DISCUSSIONThe heritability of Aβ42/40 (16%) is lower than the heritability of AD, suggesting strong environmental influences on this biomarker. The lack of correlation between NfL/GFAP and Aβ42/40 indicates these markers may be on different biological pathways.Highlights Heritability is found for glial fibrillary acidic protein (60%), neurofilament light chain (42%), and amyloid beta (Aβ) 42/40 (16%) plasma levels. Aβ42/40 plasma levels are sensitive to person‐specific environmental influences.