Genetic risk factors in Japanese Alzheimer's disease patients: alpha1-ACT, VLDLR, and ApoE.

We studied the polymorphism of alpha1-antichymotrypsin (ACT), very low density lipoprotein receptor (VLDLR) and apolipoprotein E (ApoE) genes in 200 control subjects and 65 patients with Alzheimer's disease (AD) in Japanese. The subjects consisted of 30 patients with early onset familial Alzheimer's disease (FAD), a patient with late onset FAD, 29 patients with an early onset isolated form of AD, and 5 patients with late onset AD. ApoE genotypes were significantly different between controls and FAD (p < 0.0005) or AD (p < 0.05), and patients carrying at least one ApoE epsilon4 allele were found in 44% of FAD and 34.3% of AD; both were significantly different (p < 0.001) from the controls (12.5%). ACT genotypes and allele frequencies were not different among these groups except for genotypes between ApoE epsilon4 FAD and ApoE epsilon4 controls (p = 0.019). There was a slight but significant increase of the 5 repeat allele of VLDLR in AD (p = 0.014), but the difference was rather diminished in the presence of an ApoE epsilon4 allele. None of combinations of ACT and VLDLR genotypes in the presence or absence of an ApoE epsilon4 allele gave significant difference. Thus, we conclude that among the reported genetic risk factors, ApoE epsilon4 is the only definite risk factor for both FAD and AD, and the VLDLR polymorphism might be associated with AD cases in Japanese.