Genetic Risk Factors in Alzheimer’s Disease

A functional polymorphism of the brain-derivedneurotrophic factor (BDNF Val66Met) has been reported to affectmemory-related hippocampal activity. Apolipoprotein E (ApoE)gene polymorphism is known to be associated with Alzheimerdisease (AD), dementia with Lewy bodies (DLB), and Pick disease(PiD). We tested the hypothesis that BDNF Val and ApoE e4alleles confer susceptibility to AD, DLB, and PiD. The studyincluded 160 AD, 34 DLB patients, 38 autopsy-confirmed PiD, and164 age-matched healthy control (HC) probands. The frequency ofthe BDNF Val allele was significantly higher in AD, but there wereno statistical differences in the allele distribution in PiD or in DLBas compared with HC. The Val/Met genotype occurred withstatistically significantly higher frequency in PiD than in HC. TheApoE e4 allele was significantly overrepresented in all dementias ascompared with HC. Genotypes containing both ApoE e4 andBDNF Val alleles occurred more frequently in all investigateddementias than in HC. We suggest that the presence of the BDNFVal allele in itself and in combination with the ApoE e4 allele canbe risk factors for AD, and the results indicate a synergistic effect ofthe 2 polymorphisms on DLB and PiD risk.