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Autoimmune mice as models for discovery of drugs against age‐related dementia

The discovery and development of drugs to treat Alzheimer's disease and other age‐associated dementias constitute an important goal of research in the pharmaceutical industry. Suitable animal models are routinely sought to expedite the discovery and development processes. The current review proposes new animal models based upon research findings from both clinical and animal investigations which suggest a neuroimmunologic component in certain age‐associated dementias. Several clinical studies are discussed which suggest associations between dementia and brain‐reactive autoantibodies in patients with Alzheimer's disease. In addition, studies of mice suggest that neuroimmunological, neuropathological, and behavioral characteristics of aging are accelerated in genetically autoimmune‐prone mice. The learning and memory deficits of autoimmune mice are qualitatively similar to those of normal aged mice, and these deficits show similar sensitivity to pharmacologic interventions involving cholinergic and GABNbenzodiazepine systems. However, the appearance and progression of these changes with age occur more rapidly and with greater reliability in the autoimmune mice when compared with non‐autoimmune strains. The studies reviewed suggest that autoimmune mice may provide a useful animal model for identification and evaluation of new drugs against learning and memory dysfunctions. In addition, the accelerated decline of learning/memory in autoimmune mice may expedite evaluation of chemical interventions designed to prevent the occurrence or arrest the progress of Alzheimer's disease and other age‐associated dementias. The autoimmune models may be especially appropriate in identifying novel drugs with the immune system as a primary target.