The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced hippocampus perfusion in frontotemporal lobar degeneration.

Brain-derived neurotrophic factor (BDNF) promotes several functions in neurons and modulates neurotransmissions, especially in hippocampal regions. Frontotemporal lobar degeneration (FTLD) has a strong genetic background, but genetic risk factors associated with sporadic disease are unknown. Hippocampal involvement is frequently observed in FTLD. The aims of this study were: i) to evaluate if BDNF genetic variations are associated with an increased risk of developing FTLD; and ii) to assess the neuroimaging profiles associated with BDNF polymorphisms. Ninety-one FTLD patients who underwent SPECT imaging and blood sampling entered the study, and clinical, cognitive, and behavioral examinations were performed. A larger group of FTLD patients (n = 194) and controls (n = 396; 162 healthy subjects and 234 Alzheimer's disease (AD) patients) underwent genetic analyses, considering BDNF polymorphisms (Val66Met, rs2049045 C/G, G11757C). A significant different distribution of G11757C genotype in FTLD (GG 53.1%, GC 42.8%, CC 4.1%) compared to controls (G/G 55.6%, G/C 34.6%, C/C 9.8%, p = 0.020) was found. No other significant differences in genotype and allele distributions were detected. The effect of BDNF polymorphisms on brain perfusion was analyzed. BDNF Val66Met A* carriers (A/A or G/A) showed a significant greater hypoperfusion parahippocampal regions as compared to G/G carriers (p < 0.005). No effect of G11757C polymorphism on brain perfusion was found. rs2049045 C/G was not considered as in linkage disequilibrium with Val66Met polymorphism. BDNF Val66Met polymorphism may play a role as a modulator of the FTLD expression and may drive a selective damage in specific brain region affected by the disease.