Amyloid Abeta in the natural history of Alzheimer's disease

点击翻译按钮获取中文摘要

This grant is the continuation of a large series of experiments designed to uncover the basic causes of Alzheimer's disease. The focus is on closing some of the gaps in our knowledge of the natural history of Alzheimer's disease in relation to the deposition of the Abeta amyloid protein in the brain, which we believe plays a central role in the degeneration of nerve cells in this condition. The main questions we are tackling include: the feasibility of using assays of Abeta in the blood as a biological marker of Alzheimer's disease; whether better transgenic mouse models of Alzheimer's disease are required; whether the soluble forms of Abeta amyloid are the major species which cause neurotoxicity (in contrast to the insoluble forms which constitute the bulk of this protein in the Alzheimer's disease brain); and whether the intracellular or extracellular pathways of Abeta aggregation and toxicity are the key to understanding this disease. Increasing evidence suggests that the clearance of soluble forms of the Abeta protein from the brain may be a major therapeutic strategy. We therefore require further investigations of how these soluble forms of Abeta are generated in nerve cells, and how these forms exist in equilibrium with soluble and insoluble pools in the brain, cerebrospinal fluid, blood and other tissues of the body.