Risk of late-onset Alzheimer's disease associated with BDNF C270T polymorphism

We examined the frequency of the T allele of the C270T polymorphism of the brain-derived nerve growth factor (BDNF) gene in a test and replication test design. Our objective was to determine if there is an association between the BDNF gene and Alzheimer's Disease (AD) in a US population. There were 106 autopsy-proven AD cases and 101 controls of similar ages in each test for a total of 212 AD cases and 202 controls. We found that there was a significant increase in the T allele in both the initial set (p = .04) and in the replication set (p = .018). For both groups combined p = .0008. Odds ratio = 3.28, 95% CI = 1.69-6.34. There were 54 cases of early-onset AD (EOAD) and 159 cases of late-onset AD (LOAD). The results were only significant for LOAD, p = .0002, odds ratio = 3.81, 95% CI = 1.93-7.52. The r(2) or fraction of the variance attributed to the BDNF gene for the LOAD cases was .046. The results were independent of the APOE epsilon 4 allele. When the younger controls were removed, providing a close age match to the AD subjects, the frequency of the T allele was even lower and the differences were still significant for both total AD and LOAD cases. In a logistic regression analysis including APOE, age, sex and BDNF, BDNF was significant at p < .0001. We concluded that BDNF gene variants are significant risk factors for late onset AD. (c) 2005 Published by Elsevier Ireland Ltd.