BDNF and Alzheimer disease: However, genetic down-regulation of BDNF (heterozygous gene knockout) in AD mouse models does not result in exacerbated AD-like pathology (Castello et al., 2012), although these mice harbor BDNF deficits throughout their entire lives and may develop compensatory mechanisms that overcome the effect of reduced BDNF (Rantamäki et al., 2013).