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

Abstract: 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 investigatedin association with gene polymorphisms of BDNF (Val66Met and C270T), of some oxidative stressrelatedgenes (FOXO3A, SIRT3, GLO1, and SOD2), and of interleukin-1 family genes (IL-1, IL-1,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 BDNFcompared with controls (p = 0.010). Moreover, lower BDNF was associated with the presence of theT mutant allele of IL-1(rs1800587) in AD (p = 0.040). These results were even more significant inthe female subsets (BDNFVal/Val, p = 0.001; IL-1, p = 0.013; males: ns). In conclusion, reducedserum levels of BDNF were found in AD; polymorphisms of the IL-1 and BDNF genes appear to beinvolved in changes in serum BDNF, particularly in female patients, while no effects of other genevariants affecting oxidative stress have been found. These findings add another step in identifyinggender-related susceptibility to AD.