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.