Animal models of Alzheimer's disease: therapeutic implications.

This Special Issue of the Journal of Alzheimer's Disease (JAD) provides an overview of animal models of Alzheimer's disease (AD). Very few species spontaneously develop the cognitive, behavioral, and neuropathological symptoms of AD, yet AD research must progress at a more rapid pace than the rate of human aging. In recent years, a variety of models have been created--from tiny invertebrates with life spans measurable in months to huge mammals that live several decades. The fruit fly, Drosophila melanogaster, is a powerful genetic tool that has recently emerged as a model of AD with neural features and assessable learning and memory. Transgenic mice are the most widely used animal models of AD and have yielded significant research breakthroughs. Accelerated aging seen in the SAMP8 mouse is a non-transgenic model with great utility. Rat models provided early evidence about the deleterious impact of amyloid-beta (Abeta) on neurons and continue to provide insights. Rabbits, as langomorphs, are more closely related to primates than are rodents and have conserved the sequence of Abeta in humans (as have canines and non-human primates). The hypercholesterolemic rabbit is an excellent AD model. The aging canine develops AD neuropathology spontaneously and is especially suitable for tests of therapeutics. Non-human primates are invaluable for the development of therapeutics translating to humans. Each animal model has limitations and strengths, but used together in complementary fashion, animal models for research on AD are essential for rapid progress toward a cure.