Alzheimer's disease and tauopathy studies in flies and worms

Progressive dementias like Alzheimer's Disease (AD) and other tauopathies are an increasing threat to human health worldwide. Although significant progress has been made in understanding the pathogenesis of these diseases using cell culture and mouse models, the complexity of these diseases has still prevented a comprehensive understanding of their underlying causes. As with other neurological diseases, invertebrate models have provided novel genetic approaches for investigating the molecular pathways that are affected in tauopathies, including AD. This review focuses on transgenic models that have been established in Drosophila melanogaster and Caenorhabditis elegans to investigate these diseases, and the insights that have been gained from these studies. Also included are a brief description of the endogenous versions of human "disease genes" (like tau and the Amyloid Precursor Protein) that are expressed in invertebrates, and an overview of results that have been obtained from animals lacking or overexpressing these genes. These diverse models can be used to advance our knowledge about how these proteins acquire a pathogenic function and how disrupting their normal functions may contribute to neurological pathologies. They also provide powerful assays for identifying molecular and genetic interactions that are important in developing or preventing the deleterious effects.