Polygenic risk for Alzheimer's disease is associated with neuroaxonal damage before onset of clinical symptoms

Abstract INTRODUCTION Establishing valid diagnostic strategies is a precondition for successful therapeutic intervention in Alzheimer's disease (AD). METHODS One hundred forty‐four healthy 75‐year‐old participants from the Vienna‐Transdanube‐Aging longitudinal cohort study were tested for neuroaxonal damage by single molecular array (Simoa) plasma neurofilament light chain (NfL) levels at baseline, 30, 60, and 90 months, and onset of AD dementia. Individual risk for sporadic AD was estimated by continuous shrinkage polygenic risk score (PRS‐CS, genome‐wide association study). RESULTS Nineteen participants developed AD after a median of 60 months (interquartile range 30). In participants with AD, baseline NfL plasma levels correlated with PRS‐CS (r = 0.75, p