Effects of APOE genotype on amyloid PET positivity according to cognitive status and ethnicity

Abstract

AbstractBackgroundAmong the various risk factors for Alzheimer disease (AD), apolipoprotein E (APOE) genotype ε4 is known to be a strong factor. On the other hand, ε2 is known to have a protective effect. It is not yet clear how amyloid positivity according to the APOE genotype differs by diagnostic criteria. Also, there were no studies showing the ethnic difference in the effects of APOE genotype on amyloid‐beta (Aβ) between American and Asian. The aim of this study was to investigate how Aβ positivity (Aβ+) according to APOE genotypes differs by ethnicity and cognition.MethodWe recruited 4,203 Korean subjects from multi‐centers in South Korea and 1,069 subjects from Alzheimer’s Disease Neuroimaging Initiative database. All subjects underwent neuropsychological tests, APOE genotype tests, and amyloid PET (FMM/FBB/AV45) scans. Subjects with the ε2/ε4 genotype were excluded due to the opposing effects of the ε4 and ε2 alleles. The degree of influence on amyloid positivity by each factor was analyzed by logistic regression.ResultThe frequency of Aβ+ in normal cognition (NC) group was higher in ADNI than in Korean group (p <0.001). Amnestic mild cognitive impairment and AD dementia (ADD) groups showed no difference in the frequency of Aβ+ between ADNI and Korean groups. Relative to APOE ε3/ε3 group, APOE ε4 carriers showed higher frequent Aβ+ regardless of cognitive status and ethnicity (Figure). ADNI and Korean groups showed APOE ε2 carriers less frequent Aβ+ in ADD but not in NC relative to APOE ε3/ε3 group.ConclusionOur findings suggested that there were no differences in effects of APOE ε4 genotype on Aβ+ between European and Korean. These findings will be helpful in predicting amyloid positivity and AD intervention according to APOE genotype and ethnicity.