Association of APOE promoter but not A2M polymorphisms with risk of developing Alzheimer's disease

The APOE4 allele is widely accepted as a major risk factor for late-onset A lzheimer's disease (AD). Recently, it has been reported that polymorphisms in the APOE promoter and in the alpha2-macroglobulin gene (A2M) are associa ted with AD. We have analyzed the distribution of APOE alleles, -219T/G APO E promoter polymorphism and A2M/A2Mdel polymorphism in a large case-control study. Our results showed that APOE genotype was the only informative mark er of AD risk contrary to -219T/G and A2M/A2Mdel polymorphism. in AD patien ts however, a strong linkage disequilibrium was observed between the T alle le of -219T/G polymorphism and APOE4 allele. This result indicates that -21 9T/G APOE promoter polymorphism is a risk factor for AD by increasing the A POE4-associated risk. NeuroReport 11:3599-3601 (C) 2000 Lippincott Williams & Wilkins.