The Toxicity and Polymorphism of β-Amyloid Oligomers

It is widely accepted that beta-amyloid oligomers (A beta os) play a key role in the progression of Alzheimer's disease (AD) by inducing neuron damage and cognitive impairment, but A beta os are highly heterogeneous in their size, structure and cytotoxicity, making the corresponding studies tough to carry out. Nevertheless, a number of studies have recently made remarkable progress in the describing the characteristics and pathogenicity of A beta os. We here review the mechanisms by which A beta os exert their neuropathogenesis for AD progression, including receptor binding, cell membrane destruction, mitochondrial damage, Ca(2+)homeostasis dysregulation and tau pathological induction. We also summarize the characteristics and pathogenicity such as the size, morphology and cytotoxicity of dimers, trimers, A beta*56 and spherical oligomers, and suggest that A beta os may play a different role at different phases of AD pathogenesis, resulting in differential consequences on neuronal synaptotoxicity and survival. It is warranted to investigate the temporal sequence of A beta os in AD human brain and examine the relationship between different A beta os and cognitive impairment.