Gene- and Gender-Related Decrease in Serum BDNF Levels in Alzheimer's Disease

Brain-derived neurotrophic factor (BDNF) has a protective role in Alzheimer's disease (AD). Oxidative stress and inflammatory cytokines are potentially implicated in AD risk. In this study, BDNF was detected in serum of AD and mild cognitive impairment (MCI) patients and investigated in association with gene polymorphisms of BDNF (Val66Met and C270T), of some oxidative stress-related genes (FOXO3A, SIRT3, GLO1, and SOD2), and of interleukin-1 family genes (IL-1α, IL-1β, and IL-38). The APOE status and mini-mental state examination (MMSE) score were also evaluated. Serum BDNF was significantly lower in AD (p = 0.029), especially when comparing the female subsets (p = 0.005). Patients with BDNFVal/Val homozygous also had significantly lower circulating BDNF compared with controls (p = 0.010). Moreover, lower BDNF was associated with the presence of the T mutant allele of IL-1α(rs1800587) in AD (p = 0.040). These results were even more significant in the female subsets (BDNFVal/Val, p = 0.001; IL-1α, p = 0.013; males: ns). In conclusion, reduced serum levels of BDNF were found in AD; polymorphisms of the IL-1α and BDNF genes appear to be involved in changes in serum BDNF, particularly in female patients, while no effects of other gene variants affecting oxidative stress have been found. These findings add another step in identifying gender-related susceptibility to AD.