The heritability of blood‐based biomarkers related to risk of Alzheimer's disease in a population‐based sample of early old‐age men
Nathan A. Gillespie, Jeremy A. Elman, Ruth McKenzie, Xin Tu, Hong Xian, Chandra A. Reynolds, Matthew S. Panizzon, Michael J. Lyons, Graham M.L. Eglit, Michael C. Neale, Robert A. Rissman, Carol E. Franz, William S. Kremen
Abstract
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.