Ab peptide oligomers - potential neurotoxic agents in Alzheimer disease

Amyloid beta peptide (Abeta) is recognized as the main constituent of the extracellular amyloid plaques, the major neuropathological hallmark of Alzheimer's disease (AD). Abeta is a small peptide present in normal cells, not toxic in the monomeric form but aggregated Abeta is assumed to be the main if not the only factor causing Alzheimer's disease. Interestingly, the new reports suggest neurotoxicity of soluble Abeta oligomers rather then amyloid fibrils. Due to the fact that fibrils were thought to be the main toxic species in AD, early structural studies focused on fibrils themselves and Abeta monomers, as their building blocks, while there is practically no data on oligomer structure and mechanism of neurotoxicity. Thus a new area of research opened, focusing on Abeta soluble oligomers and the results of the studies will be reviewed here.