BNDF modulates normal human hippocampal ageing

Brain-derived neurotrophic factor (BDNF), a neutrophin highly expressed in the hippocampus, has been associated with hippocampal-dependent learning and memory processes.1 A polymorphism in the BDNF (BDNFval66met; rs6265) gene causing a valine (val)-to-methionine (met) substitution at codon 66 results in altered intracellular trafficking and packaging of BDNF, and in a reduction of its regulated secretion.1 BDNFval66met genotype predicts variation in human episodic memory, as well as in hippocampal anatomy and function.1,2 In rats, BDNF-mediated beneficial effects on neuroprotection, memory ability and learning decrease with advancing age.3 Interestingly, hippocampal activity in humans,4 as well as the expression of BDNF and its receptor5 in this region also decrease with age. In line with these findings, we expected that age-related decline of hippocampal function would be modulated by genetically determined variation in BDNF function, such that BDNF-met allele carriers (expressing diminished regulated secretion of BDNF) would show a more pronounced decrease in memory-dependent hippocampal activity with advancing age relative to BDNF-val/val individuals.