Genetic and environmental contributions to variation in plasma phosphorylated tau 217

INTRODUCTION Plasma phosphorylated tau 217 (p‐au217) is a promising Alzheimer's disease (AD) biomarker. Little is known about the causes of variance in p‐tau217 concentrations in cognitively unimpaired populations. METHODS The present sample included cognitively healthy twins and their family members ( n = 6495). Biometric twin models were used to determine relative genetic and environmental contributions to variance in p‐tau217, and genetic and environmental correlations between p‐tau217 and neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta 42/40 (Aβ42/40). RESULTS Genetic contributions accounted for 42% (males) and 41% (females) of variance in p‐tau217. Half of the genetic effects were sex specific. Genetic and environmental contributions to p‐tau217 were partially shared with NfL, GFAP, and Aβ42/40, but different patterns were found in males and females. DISCUSSION P‐tau217 concentrations are moderately heritable. Sex‐specific genetic influences are found to act on p‐tau217. In cognitively unimpaired participants, p‐tau217 and Aβ42/40 reflect different biological processes. Highlights Phosphorylated tau (p‐tau)217 concentrations are substantially heritable (> 41%). Genetic contributions to variation in plasma p‐tau217 were found to be sex specific. Genetic and environmental correlations were found between p‐tau217 and Alzheimer's disease biomarkers. P‐tau217 reflects different processes in cognitively unimpaired males and females.