Abstract
INTRODUCTION: Apolipoprotein E (APOE) epsilon4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta (Abeta) pathology. METHODS: We included 3451 Abeta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon4 prevalence in relation to age, sex, education, and geographical location. RESULTS: The APOE epsilon4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Abeta+ cognitively normal and Abeta+ mild cognitive impairment (P < .05) but not in Abeta+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. DISCUSSION: The APOE epsilon4 prevalence in AD was higher than that in previous studies, which did not require presence of Abeta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
