Age-dependent effects of APOE ?4 in preclinical Alzheimer's disease.

ABSTRACT: The ?4 allele of apolipoprotein E (APOE) is the strongest known common genetic risk factor for Alzheimer's disease (AD) and alters age of onset in retrospective studies. Here, we longitudinally test the effects of APOE ?4 genotype and age during progression from normal cognition to AD.Using data from 5381 cognitively normal older individuals and Cox proportional hazards models, we longitudinally tested the effects of APOE genotype on progression from normal cognition to mild cognitive impairment (MCI) or AD in four age strata (<60, 60-70, 70-80, 80 + ) and with a sliding window approach between ages 60 and 85.We found that APOE ?4 carrier status and dosage significantly influenced progression to MCI or AD in all four age groups and that APOE ?4-associated progression risk peaked between ages 70 and 75. We confirmed APOE ?4-associated progression risk in a subset of the cohort with pathologically proven diagnoses.Our findings indicate that in clinically normal individuals, APOE ?4 status significantly predicts progression to MCI or AD across older adulthood and that this risk varies with age. This information will be useful as therapeutic interventions become available and clinical decisions can be individually tailored based on age and genetic data.

SUBMITTER: Bonham LW 

PROVIDER: S-EPMC5018579 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature