Neurotrophic factor strategies for the treatment of Alzheimer disease

Cholinergic neurons in the nucleus basalis of Meynert are reduced early in the course of Alzheimer disease, and the dysfunction of cholinergic neurons is believed to be primarily responsible for cognitive deficits in the disease. Nerve growth factor has a trophic effect on cholinergic neurons and therefore may have some beneficial effects on the cognitive impairment observed in patients with Alzheimer disease. Experimental studies demonstrated that a continuous infusion of nerve growth factor into the cerebroventricle prevents cholinergic neuron atrophy after axotomy or associated with normal aging and ameliorates cognition impairment in these animals. A clinical study in three patients with Alzheimer disease revealed, however, that a long-term intracerebroventricular infusion of nerve growth factor may have certain potentially beneficial effects, but the continuous intracerebroventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects. Several other strategies have been suggested to provide neurotrophic support to cholinergic neurons. In this article, we review the neurotrophic factor strategies for the treatment of Alzheimer disease.