Models of Alzheimer's Disease

This chapter describes a number of the best characterized natural and transgenic animal models for Alzheimer's disease (AD) along with the caveats that each presents for studying mechanisms of disease and for testing of potential therapeutic strategies. Alzheimer's disease afflicts primarily the higher order processing regions of the cerebral cortex and associated subcortical nuclei. A key issue for AD model development is whether AD is a pathological process or whether it is part of the normal sequence of aging. The yeast, Saccharomyces cerevisiae, allows the use of powerful classical and molecular genetic tools, although this organism lacks a nervous system. The roundworm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, are well-studied animals that are also genetically accessible. Drosophila and C. elegans provide both powerful genetic tools and a sufficiently complex behavioral repertoire to be able to detect alterations in brain function. The symptomatic approach to treating AD involves maintaining or restoring the neuronal pathways that become deficient during the course of the disease.