Apolipoprotein E and α1-antichymotrypsin genotypes and age of onset of familial Alzheimer's disease

Apolipoprotein E (APOE) and alpha(1)-antichymotrypsin (ACT) genotype and allele frequency distribution were investigated in 113 familial Alzheimer's disease (AD) cases. A significantly higher epsilon 4 frequency was observed in patients with an age of onset between 55-64 and 65-74 years compared to individuals with later or earlier onset, No difference in ACT A allele frequency was seen in any onset group, nor was any influence of ACT genotypes on the age of onset observed, However, the mean age of onset was lowered by the presence of the ACT/AA and ACT/TT genotypes among APOE epsilon 3/3 bearers. Possible APOE effects on age of onset were evaluated in 78 affected sib pairs. An earlier age of onset was observed in siblings with an epsilon 4 allele compared to siblings without an epsilon 4 allele. This supports the notion that the epsilon 4 allele promotes an earlier age of onset. However, in siblings with the same APOE genotype, a wide range of onset was seen, indicating that unknown genetic or environmental factors affect the expression of AD.