Amyloid-beta Oligomers: Possible Roles As Key Neurotoxins in Alzheimer's Disease

Alzheimer's disease is the most common form of senile dementia. Although the amyloid-beta peptide was identified in 1984 as the major constituent of the senile plaques that characterize the disease, accumulating evidence indicates that the plaque density does not correspond well to the concurrent disease state. In order to resolve this disconnect, a number of recent studies have shifted away from the senile plaque and classical fibrillar forms of amyloid toward a less well structured species as the proximate neurotoxic factor underlying cognitive failure in Alzheimer's disease: soluble amyloid-beta peptide oligomer (also known as the amyloid-beta peptide-derived diffusible ligand). Paradoxically, several studies in the last 2 years have shown that picomolar levels of amyloid-beta peptide have neutral activity or perhaps even an essential role in learning and memory. Here we highlight some of the key observations underlying the growing focus on the amyloid-beta peptide oligomer.