Promises of animal models of Alzheimer disease

Abstract

The hypothesis that a cholinergic deficit might be responsible for memory impairment was based on studies showing learning and memory deficits in animals and humans whose cholinergic system was blocked by atropine or scopolamine (Drachman, 1977). Confirmation was sought by animal investigations in which the forebrain cholinergic nuclei were destroyed, initially by electrolytic lesions, then by excitotoxins and finally by the selective immunotoxins 192 IgG-saporin (Wenk et al., 1994). Intracerebroventricular (i.c.v.) injection of 192 Ig-G-saporin brings about a widespread degeneration of cholinergic neurons including the nucleus basalis of Meynert and the septum (Lin et al., 1999). The reversion of the learning and memory deficits induced by nucleus basalis of Meynert lesions has become a classical preclinical test for the screening of drugs aimed to correct the cholinergic hypo-function in AD (see Pepeu, 2000).