[Causative genes in Alzheimer's disease]

Recently, some Alzheimer-associated genes have been found: amyloid precursor protein (APP), apolipoprotein E (apoE), presenilin 1 (PS-1) and presenilin 2 (PS-2). First, we examined mutations of APP, PS-1, and PS-2 genes in familiar Alzheimer's disease (FAD) (7 cases) found in San-in district by single-strand conformation polymorphism and sequence analysis. These seven cases with FAD did not show any mutations of APP, PS-1, and PS-2 genes. Other susceptibility genes of FAD still remain to be not identified. Many reports have established that apoE genotype distribution for the epsilon 4 allele is a susceptibility factor for the earlier onset and more rapid progression of Alzheier's disease (AD). However, the cause of sporadic AD (SAD) has not been elucidated fully. Other genetic factors may be associated with development of SAD. Second, we investigated the association between polymorphisms of the estrogen receptor (ER) alpha gene and SAD. The frequencies of P and X alleles in SAD were significantly higher than those in the control group (p < 0.05). Polymorphisms of the ER alpha gene may be a genetic risk factor for SAD. The apoE genotype is a genetic factor closely related SAD, but it is not full by appreciated how apoE has an effect on developing AD. There are few reports on the quantitative change of apoE, namely the expression of apoE mRNA. Third, ApoE mRNA level in the brains of patients with Alzheimer's disease (27 cases) and Down's syndrome (11 cases) was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). ApoE mRNA level in the DS as well as AD was significantly higher than that in control group (p < 0.05, p < 0.05, respectively). High levels of apoE mRNA in AD and DS may play an important role in the development of Alzheimer pathology.