BDNF and Alzheimer disease: In this regard, it is somewhat sobering that rescue of reduced levels of BDNF in the hippocampus and entorhinal cortex by sustained BDNF gene delivery via viral vectors, in subjects with AD, did not have significant clinical efficacy (Connor et al., 1997; Hock et al., 2000; Nagahara and Tuszynski, 2011), although it does encourage the search for novel, alternative therapeutics that activate these pathways and may have better clinical results.