A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease

Several lines of evidence have suggested altered functions of the brain-der ived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative di seases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a no vel nucleotide substitution (C270T) in the noncoding region. We performed a n association study between this polymorphism and AD in a Japanese sample o f 170 patients with sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency of individuals who carried the mutated type (T270) was significantly more common in patients with late-onset AD than in contr ols (P = 0.00004, odds ratio: 3.8, 95% CI 1.9-7.4). However, there was no s ignificant difference in the genotype distribution between the patients wit h early-onset AD and the controls, although this might be due to the small sample size of the early-onset group. Our results suggest that the C270T po lymorphism of the BDNF gene or other unknown polymorphisms, which are in li nkage disequilibrium, give susceptibility to late-onset AD. We obtained no evidence for the possible interactions between the BDNF and apolipoprotein E (APOE) genes, suggesting that the possible effect of the BDNF gene on the development of late-onset AD might be independent of the APOE genotype.