Aβ aggregation and possible implications in Alzheimer's disease pathogenesis

Introduction Amyloid Structure Mechanism of Amyloid aggregation A beta: a natively unfolded protein ? Ambiguities in synthetic Ab studies Formation of Amyloid plaques Role of Ab in AD Pathogenesis Conclusion Amyloid beta protein (A beta) has been associated with Alzheimer's disease (AD) because it is a major component of the extracellular plaque found in AD brains. Increased A beta levels correlate with the cognitive decline observed in AD. Sporadic AD cases are thought to be chiefly associated with lack of A beta clearance from the brain, unlike familial AD which shows increased A beta production. A beta aggregation leading to deposition is an essential event in AD. However, the factors involved in A beta aggregation and accumulation in sporadic AD have not been completely characterized. This review summarizes studies that have examined the factors that affect A beta aggregation and toxicity. By necessity these are studies that are performed with recombinant-derived or chemically synthesized A beta. The studies therefore are not done in animals but in cell culture, which includes neuronal cells, other mammalian cells and, in some cases, non-mammalian cells that also appear susceptible to A beta toxicity. An understanding of A beta oligomerization may lead to better strategies to prevent AD.