PMID- 22596272 OWN - NLM STAT- MEDLINE DCOM- 20130604 LR - 20131121 IS - 1875-8908 (Electronic) IS - 1387-2877 (Linking) VI - 31 IP - 2 DP - 2012 TI - The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced hippocampus perfusion in frontotemporal lobar degeneration. PG - 243-51 LID - 10.3233/JAD-2012-120226 [doi] AB - 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. FAU - Borroni, Barbara AU - Borroni B AD - The Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy. bborroni@inwind.it FAU - Bianchi, Marta AU - Bianchi M FAU - Premi, Enrico AU - Premi E FAU - Alberici, Antonella AU - Alberici A FAU - Archetti, Silvana AU - Archetti S FAU - Paghera, Barbara AU - Paghera B FAU - Cerini, Carlo AU - Cerini C FAU - Papetti, Alice AU - Papetti A FAU - Padovani, Alessandro AU - Padovani A LA - eng PT - Journal Article PL - Netherlands TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 0 (Brain-Derived Neurotrophic Factor) RN - AE28F7PNPL (Methionine) RN - HG18B9YRS7 (Valine) SB - IM MH - Aged MH - Aged, 80 and over MH - Brain-Derived Neurotrophic Factor/*genetics MH - Female MH - Frontotemporal Lobar Degeneration/diagnosis/*genetics/physiopathology MH - Hippocampus/*blood supply/physiology MH - Humans MH - Male MH - Methionine/*genetics MH - Middle Aged MH - Polymorphism, Genetic/*genetics MH - Valine/*genetics EDAT- 2012/05/19 06:00 MHDA- 2013/06/05 06:00 CRDT- 2012/05/19 06:00 PHST- 2012/05/19 06:00 [entrez] PHST- 2012/05/19 06:00 [pubmed] PHST- 2013/06/05 06:00 [medline] AID - B30T534112027VX4 [pii] AID - 10.3233/JAD-2012-120226 [doi] PST - ppublish SO - J Alzheimers Dis. 2012;31(2):243-51. doi: 10.3233/JAD-2012-120226.