Genetic architecture of Alzheimer's disease-related plasma biomarkers

INTRODUCTIONAlzheimers disease-related plasma biomarker interrelationships and factors underlying these associations remain poorly understood. To address this, we studied the heritability of plasma biomarkers and their associations with cognition. METHODSThis study included 696 twins, aged 65-85, without a diagnosis of Alzheimers disease. Plasma amyloid beta 42 and 40, phosphorylated tau (p-tau) 181 and 217, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified with Simoa HD-X, and cognition was assessed with cCOG. Statistical analyses were done with multivariate twin models and linear mixed effect models. RESULTSPhenotypic associations between p-tau181, p-tau217, NfL and GFAP were 0.22-0.73. Heritability estimates were 0.39-0.66, and genetic correlations were 0.32-0.67. P-tau181 and p-tau217 were associated with cognition ({beta} = -0.12; 95% CI: -0.19--0.04 and {beta} = -0.19; 95% CI: -0.26--0.12, respectively). DISCUSSIONThe observed phenotypic and genetic associations highlight shared underlying mechanisms among plasma biomarkers.