Cognitive Performance in Young APOE ε4 Carriers: A Latent Variable Approach for Assessing the Genotype–Phenotype Relationship

Abstract

The ε4 allele of the apolipoprotein (APOE) gene is a widely recognized genetic risk factor for developing Alzheimer’s disease in older age. However, it is controversial whether there is a positive impact of the APOE ε4 allele on human cognitive performance in young adulthood, possibly representing a case of antagonistic pleiotropy. Here we explored associations of the APOE ε4 allele with cognitive ability in young adulthood. In contrast to previous studies, we used structural equation modeling that allows a multivariate measurement of the cognitive phenotype. Results based on four independent samples (N1 = 245; N2 = 300; N3 = 244; N4 = 206) overall revealed a complex effect of the APOE ε4 genotype on cognitive ability in young adulthood: Whereas the ε4 allele tends to be negatively associated with cognitive performance in individuals with lower education levels, there might be a weak positive association in persons with higher education—a finding that is partly in line with the antagonistic pleiotropy view on APOE and cognitive ability. The education-related findings support protective effects of environmental factors.