An attempt to cause the selective loss of the cholinergic neurons in the basal forebrain of the rat: A new animal model of Alzheimer's disease

Abstract In the present study, we attempted to develop a new animal model of Alzheimer's disease. Injections of a nerve growth factor (NGF)-diphtheria toxin conjugate into the cerebral cortex resulted in a marked ipsilateral reduction of cholinergic neurons in the horizontal limb of the diagonal band and basal magnocellular nucleus of rats. No effects could be seen in the cholinergic neurons located in the laterodorsal tegmental nucleus intrinsic cortical cholinergic neurons, and catecholaminergic locus coeruleus neurons. Injections of the conjugate into the caudoputamen failed to cause changes in the striatal cholinergic neurons. Since our method could selectively reduce cholinergic neurons in the basal forebrain without damage to the non-cholinergic neurons or passing fibers in this nucleus, this animal model method seems to be very useful in analyzing the pathogenesis of Alzheimer's disease or in examining the function of acetylcholine in the cholinergic neurons of the basal forebrain.