In line with in vivo evidence concerning the potential initial role of basal forebrain degeneration in AD onset/progression (Beach et al., 2000; Roher et al., 2000; Grothe et al., 2013; Schmitz et al., 2016), these results help to clarify the important issue concerning the causal role of the loss in NGF-stimulated TrkA-mediated signaling in the activation of the pathogenetic amyloid cascade, suggesting that NGF deprivation is actually able to directly and locally trigger the amyloidogenic APP processing in responsive cholinergic-enriched basal forebrain neurons. The gene discussed is NGF; the disease is Alzheimer disease.