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.
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This research was supported by a scholarship awarded from Hong Kong Baptist University and an Elsa-Neumann-Scholarship from Humboldt Universität zu Berlin to Xiaojing Li. The study was also supported by a Research Group Linkage Project funded by the Alexander von Humboldt Foundation to Andrea Hildebrandt, Werner Sommer and Changsong Zhou. Behavioral data collection was funded by a grant of the Deutsche Forschungsgemeinschaft (HI 1780/2-1 & SO 177/26-1) awarded to Andrea Hildebrandt and Werner Sommer. Genetic analysis was supported by the Hong Kong Baptist University (HKBU) Strategic Development Fund and the Hong Kong Baptist University Research Committee Interdisciplinary Research Matching Scheme (IRMS/16-17/04) awarded to Changsong Zhou. The position of Christian Montag is funded by a Heisenberg grant awarded to him by the German Research Foundation (DFG, MO2363/3-2).
Conflict of interest
Xiaojing Li, Andrea Hildebrandt, Werner Sommer, Oliver Wilhelm, Martin Reuter, Christian Montag, and Changsong Zhou declare that they have no conflict of interest.
All data collections had been approved by the ethics committee of Humboldt-Universität zu Berlin (Ref.-nr. 2013-01) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was collected for all participants involved in the studies.
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Li, X., Hildebrandt, A., Sommer, W. et al. Cognitive Performance in Young APOE ε4 Carriers: A Latent Variable Approach for Assessing the Genotype–Phenotype Relationship. Behav Genet 49, 455–468 (2019). https://doi.org/10.1007/s10519-019-09961-y
- Working memory
- Secondary memory
- Structural equation modeling