Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity

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