Abstract: Introduction: Apolipoprotein E (APOE) ?4 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 ? (A?) pathology. Methods: We included 3451 A?+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ?4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ?4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A?+ cognitively normal and A?+ mild cognitive impairment (P < .05) but not in A?+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ?4 prevalence in AD was higher than that in previous studies, which did not require presence of A? pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. Keywords: APOE; Age; Alzheimer's disease; Amyloid; CSF; Education; Geographical location; Mild cognitive impairment; PET; Prevalence; Sex; Subjective cognitive decline

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