Several hypotheses can be proposed to link neurotrophic factors with neurodegenerative diseases. Not surprisingly, different hypotheses suggest completely different approaches to therapy; some would suggest use of neurotrophic factors, while others would propose that the actions of these factors be blocked. It has been suggested that NGF be used to prevent the loss of basal forebrain cholinergic neurons in Alzheimer's disease (AD). At this time it is not possible to conclude whether or not NGF is implicated in the causation or progression of this disorder. Nevertheless, experimental studies in animals have given a strong rationale for its use. Given the lack of an effective treatment for this disorder, the careful approach to NGF trials outlined by an ad hoc committee of the National Institute on Aging should be pursued.