Genetic association between APOA1 and APOD polymorphisms and Alzheimer's disease in a Japanese population

Alterations in lipoproteins are involved in the pathophysiology of Alzheimer's disease (AD). For sporadic AD, the Apolipoprotein E (APOE) is recognized as a sole genetic risk factor. Apolipoprotein A1 (APOA1) has been suggested to bind amyloid beta and promoter polymorphisms of the APOA1 gene were likely to affect the onset of the disease. Apolipoprotein D (APOD) expression is upregulating in AD brain and evidences showed APOD polymorphisms affect the risk for AD. The aim of this study was to investigate whether polymorphisms of both APOA1 and APOD genes are associated with early-onset AD (EOAD) and late-onset AD (LOAD). Common single nucleotide polymorphisms (SNPs) of the two genes were analyzed using a case-control study design. There were no associations between the two SNPs of the APOA1 gene and the onset of AD. No synergetic associations were found among the APOA1 SNPs, APOE and the risk for AD. Rs7659, 3' UTR polymorphism of the APOD gene was associated with EOAD in APOE epsilon 4 (-) subgroup. We were unable to show any impact of the other two SNPs of the APOD gene on the risk for AD. Our results suggest that the variation of the APOD gene modifies the risk for AD. Further association studies for APOD 3' UTR polymorphisms with other ethnic groups would be needed.