A primate model of Alzheimer's disease

Animal models of Alzheimer's Disease (AD) are designed to duplicate a subset of selected neuropathological, biochemical and behavioral changes that are associated with AD. One well-studied model is based upon the assumption that the destruction of basal forebrain cholinergic neurons by injection of a neurotoxin, such as ibotenic acid, is sufficient to reproduce the cognitive impairments associated with AD. Monkeys have been trained and tested in a variety of behavioral tasks that are selective for learning and memory deficits. Typically, performance was only slightly impaired, and usually recovered to control levels with continued testing. Monkeys with basal forebrain lesions were sensitive to cholinergic antagonists but did not show a consistent benefit from treatment with cholinergic agonists. Furthermore, the memory deficits did not correlate with the degree of cholinergic cell loss. Electrophysiological studies suggest that cholinergic basal forebrain cells may help to evaluate afferent sensory stimuli for degree of novelty or familiarity, or the association of the stimuli with a subsequent reward. Consistent with these findings, monkeys with basal forebrain lesions were significantly impaired in an attention task that tested spatial orienting ability. These recent studies suggest that monkeys with basal forebrain lesions may be useful as models of the attentional deficits associated with AD.