"Age-Related Olfactory Decline is Associated with the BDNF Val66met Polymorphism: Evidence from a Population-Based Study" Frontiers in Aging

Access to the published version may require subscription. nine. The met allele inhibits the intracellular trafficking and the regulated secretion of the BDNF protein at synapses (Egan et al., 2003). Several lines of evidence suggest that BDNF might be relevant for olfactory processing. It has been found to regulate the proliferation and survival of olfactory receptor neurons (ORN) in vivo (Simpson et al., 2002). In addition, the expression of BDNF is high in various parts of the CNS, including the hippocampus and the olfactory bulb (OB) although the level of expression may decrease with increasing age (Katoh-Semba et al., 1998). There is some support linking the polymorphism to olfactory functioning in animals. Bath et al. (2008) identified the BDNF val66met variant as a critical factor in the disruption of OB neurogenesis in adult BDNF and tyrosine receptor kinase (TkrB) knockout mice. The results suggest that an absence of BDNF and its receptor TkrB results in olfactory impairment. While BDNF appears necessary for the integrity of olfactory function in mice, little is known about the possible influence of the BDNF val66met polymorphism on olfactory function in humans. Behavioral association studies have demonstrated a role of the val66met polymorphism on human cognitive function. For example, individual variance in episodic memory performance and hippocampal activity has been related to the allelic combination of val66met (Egan et al., 2003). Subjects with at least one met allele have lower declarative memory performance accompanied with reduced hippocampal engagement, and smaller hippocampal volume (Egan et al. Although studies have reported that the met allele is a risk factor for cognitive impairment also in older adults