Accrual of Alzheimer's disease pathology as a function of proximity to parental dementia onset

INTRODUCTION: Whether temporal proximity to parental onset of dementia (PPO) can be used to estimate timing of the preclinical stage of sporadic Alzheimer's disease (AD) remains uncertain. METHODS: We investigated cross-sectionally adults aged > 50 without dementia included in the European Prevention of Alzheimer's Dementia (EPAD) study. PPO was tested as a predictor of quantitative levels of cerebrospinal fluid (CSF) beta-amyloid (1-42) (A beta 1-42) in those with a parental history of dementia (n = 688) and of phosphorylated tau (p-tau) and EPAD neuropsychological examination (ENE) subscores in an amyloid positive subgroup (n = 226). Possible interactions were explored. RESULTS: Shorter PPO predicted lower CSF A beta 1-42 level (beta = 9.357; T = 4.161; p < 0.001), interacting with apolipoprotein E (APOE) -epsilon 4 carriage in a dose-dependent manner. Concomitant APOE-epsilon 2 carriage appeared to provide protection. PPO did not predict p-tau levels or cognitive performance. DISCUSSION: PPO may provide a valid method of stratifying risk of early AD pathologic change in APOE-epsilon 4 carriers, with empirical and clinical applications.