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

Abstract

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) β-amyloid (1-42) (Aβ1-42) 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 Aβ1-42 level (β = 9.357; T = 4.161; p < 0.001), interacting with apolipoprotein E (APOE) -𝜀4 carriage in a dose-dependent manner. Concomitant APOE-𝜀2 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-𝜀4 carriers, with empirical and clinical applications.

Highlights: Proximity to age of parental dementia onset can predict amyloid accrualThe effect is APOE-𝜀4 dose-dependent and APOE-𝜀2 appears to provide protectionPPO does not appear to predict further advancement along the AD continuumIn the era of anti-amyloid treatments, this may inform timing of amyloid screeningUsed as an empirical metric, PPO could help elucidate the natural history of LOAD.