Transgenic models of Alzheimer's disease: learning from animals

As the scope of the problem of Alzheimer's disease (AD) grows due to an aging population, research into the devastating condition has taken on added urgency. Rare inherited forms of AD provide insight into the molecular pathways leading to degeneration and have made possible the development of transgenic animal models. Several of these models are based on the overexpression of amyloid precursor protein (APP), presenilins, or tau to cause production and accumulation of amyloid-beta into plaques or hyperphosphorylated tau into neurofibrillary tangles. Producing these characteristic neuropathological lesions in animals causes progressive neurodegeneration and in some cases similar behavioral disruptions to those seen in AD patients. Knockout models of proteins involved in AD have also been generated to explore the native functions of these genes and examine whether pathogenesis is due to loss of function or toxic gain of function in these systems. Although none of the transgenic lines models the human condition exactly, the ability to study similar pathological processes in living animals have provided numerous insights into disease mechanisms and opportunities to test therapeutic agents. This chapter reviews animal models of AD and their contributions to developing therapeutic approaches for AD.