Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity

In Alzheimer's disease (AD), insoluble and fibrillary amyloid-b (Ab) peptide accumulates in plaques. However, soluble Ab oligomers are most potent in creating synaptic dysfunction and loss. Therefore, receptors for Ab oligomers are hypothesized to be the first step in a neuronal cascade leading to dementia. A number of cell-surface proteins have been described as Ab binding proteins, and one or more are likely to mediate Ab oligomer toxicity in AD. Cellular prion protein (PrP C ) is a high-affinity Ab oligomer binding site, and a range of data delineates a signaling pathway leading from Ab complexation with PrP C to neuronal impairment. Further study of Ab binding proteins will define the molecular basis of this crucial step in AD pathogenesis.