Present imperfect: a critical review of animal models of the mnemonic impairments in Alzheimer's disease.

This paper reviews the current literature on animal models of the memory impairments of Alzheimer's disease (AD). The authors suggest that modeling of the mnemonic deficits in AD be limited to the amnesia observed early in the course of the disease, to eliminate the influence of impairments in non-mnemonic processes. Tasks should be chosen for their specificity and selectivity to the behavioral phenomena observed in early-stage AD and not for their relevance to hypothetical mnemonic processes. Tasks that manipulate the delay between learning and remembering are better able to differentiate Alzheimer patients from persons with other disorders, and better able to differentiate effects of manipulations in animals. The most commonly used manipulations that attempt to model the amnesia of AD are reviewed within these constraints. The authors conclude that of the models examined, lesions of the medial septal nucleus produce behavioral deficits that are most similar to the mnemonic impairments in the earliest stage of AD. However, the parallel is not definitive and more work is needed to clarify the relationship between neurobiology and behavior in AD.