The heritability of blood-based biomarkers related to risk of Alzheimer's disease in a population-based sample of early old-age men

Abstract

Introduction: Despite their increased application, the heritability of Alzheimer's disease (AD)-related blood-based biomarkers remains unexplored.

Methods: Plasma amyloid beta 40 (Aβ40), Aβ42, the Aβ42/40 ratio, total tau (t-tau), and neurofilament light (NfL) data came from 1035 men 60 to 73 years of age (μ = 67.0, SD = 2.6). Twin models were used to calculate heritability and the genetic and environmental correlations between them.

Results: Additive genetics explained 44% to 52% of Aβ42, Aβ40, t-tau, and NfL. The Aβ42/40 ratio was not heritable. Aβ40 and Aβ42 were genetically near identical (r_g = 0.94). Both Aβ40 and Aβ42 were genetically correlated with NfL (r_g = 0.35 to 0.38), but genetically unrelated to t-tau.

Discussion: Except for Aβ42/40, plasma biomarkers are heritable. Aβ40 and Aβ42 share mostly the same genetic influences, whereas genetic influences on plasma t-tau and NfL are largely unique in early old-age men. The absence of genetic associations between the Aβs and t-tau is not consistent with the amyloid cascade hypothesis.

Keywords: Aβ40; Aβ42; Aβ42/40 ratio; gene; heritability; neurofilament light (NfL); plasma biomarkers; total tau (t-tau); twin.