DESTRUCTION OF THE CHOLINERGIC BASAL FOREBRAIN USING IMMUNOTOXIN TO RAT NGF RECEPTOR - MODELING THE CHOLINERGIC DEGENERATION OF ALZHEIMERS-DISEASE

Degeneration of cholinergic neurons in the basal forebrain (CBF) is a prominent neuropathological feature of Alzheimer's disease and is thou ght responsible for some cognitive deficits seen in patients. An anima l model of pure CBF degeneration would be valuable for analysis of the function of these neurons and testing therapeutic strategies. CBF neu rons express receptors for nerve growth factor. In order to selectivel y destroy these neurons, we developed an immunotoxin using monoclonal antibody (192 IgG) to rat NGF receptor (p75(NGFr)) armed with the ribo some inactivating protein, saporin. In vitro 192-saporin was highly to xic to neurons expressing p75(NGFr). Intraventricular injections of 19 2-saporin destroyed the CBF and impaired passive avoidance learning. T hese results indicate that 192-saporin treated rats can be used to mod el a key feature of Alzheimer's disease and that anti-neuronal immunot oxins are a powerful approach to selective neural lesioning.