Open AccessAge‐dependent effects of APOE ε4 in preclinical Alzheimer's disease
Author(s) -
Bonham Luke W.,
Geier Ethan G.,
Fan Chun C.,
Leong Josiah K.,
Besser Lilah,
Kukull Walter A.,
Kornak John,
Andreassen Ole A.,
Schellenberg Gerard D.,
Rosen Howard J.,
Dillon William P.,
Hess Christopher P.,
Miller Bruce L.,
Dale Anders M.,
Desikan Rahul S.,
Yokoyama Jennifer S.
Publication year - 2016
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.333
Subject(s) - apolipoprotein e , medicine , disease , oncology , genotype , allele , proportional hazards model , age of onset , cognitive decline , cognition , risk factor , ageing , gerontology , dementia , psychiatry , genetics , gene , biology
Objective The ε4 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 ε4 genotype and age during progression from normal cognition to AD. Methods 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. Results We found that APOE ε4 carrier status and dosage significantly influenced progression to MCI or AD in all four age groups and that APOE ε4‐associated progression risk peaked between ages 70 and 75. We confirmed APOE ε4‐associated progression risk in a subset of the cohort with pathologically proven diagnoses. Interpretation Our findings indicate that in clinically normal individuals, APOE ε4 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.