Effect of Age, Ethnicity, and Head Injury on the Association between APOE Genotypes and Alzheimer's Disease

Tang, Mingxin; Maestre, Gladys; Tsai, Wei-Yann; Liu, Xinhua; Feng, Lin; Chung, Wai-Yee; Chun, Michael; Schofield, Peter R.; Stern, Yaakov; Tycko, Benjamin; Mayeux, Richard Paul

The apolipoprotein E (APOE)-e4 allele is neither necessary nor sufficient to cause Alzheimer's disease (AD) because it develops in the absence of APOE e4, and some persons escape the disease despite having an APOE €4 allele. Although the presence of the €4 allele of the APOE gene has been consistently associated with an increased risk of it is apparent that the degree of risk may be modified by age, gender, ethnic group, certain risk factors, and possibly other genes. Roses et al. proposed that APOE genotypes have a direct influence on the age at onset of disease. In both familial and sporadic AD, an earlier age at onset among APOE €4 homozygous and APOE €4 heterozygous cases than among those cases with other APOE genotypes. Thus, it is possible that APOE genotypes strongly influence age at onset and that certain factors, both genetic and nongenetic, modify this effect by shifting the distribution curves. In this review we will discuss demographic and putative risk factors that may modify (enhance or diminish) the association between APOE genotypes and AD.


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Annals of the New York Academy of Sciences

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February 23, 2018