[Molecular genetics of Alzheimer's disease--presenilin and other genes]

We examined mutations of presenilin 1 (PS1), presenilin 2 (PS2) and amyloid precursor protein (APP) in 30 Japanese familial Alzheimer's disease (FAD) and 34 isolated cases of Alzheimer's disease (AD). We found mutations of PS1 in 17% of early onset FAD (H163R, H163R, R269H, E273A, G384A) and in a case (H163R) of isolated AD. The remaining cases were free from mutations in PS1, PS2 and APP. Since only a part of them could he explained by ApoE epsilon 4, we concluded that important genes are missing. We also examined association of apolipoprotein E (ApoE)epsilon 4, allele A of alpha 1-antichymotrypsin (ACT), 5 repeat allele of very low density lipoprotein receptor (VLDLR) and Alzheimer's disease. We confirmed that ApoE espilon 4 is significantly more frequent in both FAD and isolated AD cases than controls. We could not see any significant association in the ACT polymorphism. The 5 repeat allele of VLDLR was slightly but significantly more frequent in AD cases than controls. However, association with ApoE epsilon 4 was not seen in our study.