Amyloid oligomers: formation and toxicity of Aβ oligomers

Alzheimer's disease (AD) is an age-related, progressive degenerative disorder that is characterized by synapse and neuron loss in the brain and the accumulation of protein-containing deposits (referred to as 'senile plaques') and neurofibrillary tangles. Insoluble amyloid beta-peptide (A beta) fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. However, accumulating evidence suggests that prefibrillar soluble A beta oligomers induce AD-related synaptic dysfunction. The size of A beta oligomers is distributed over a wide molecular weight range (from < 10 kDa to > 100 kDa), with structural polymorphism in A beta oligomers of similar sizes. Recent studies have demonstrated that A beta can accumulate in living cells, as well as in extracellular spaces. This review summarizes current research on A beta oligomers, focusing on their structures and toxicity mechanism. We also discuss possible formation mechanisms of intracellular and extracellular A beta oligomers.