title: Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity.
abstract: In Alzheimer's disease (AD), insoluble and fibrillary amyloid-β (Aβ) peptide accumulates in plaques. However, soluble Aβ oligomers are most potent in creating synaptic dysfunction and loss. Therefore, receptors for Aβ 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 Aβ binding proteins, and one or more are likely to mediate Aβ oligomer toxicity in AD. Cellular prion protein (PrPC) is a high-affinity Aβ oligomer binding site, and a range of data delineates a signaling pathway leading from Aβ complexation with PrPCto neuronal impairment. Further study of Aβ binding proteins will define the molecular basis of this crucial step in AD pathogenesis.
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06536.
authors.forename: Levi M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06536.
authors.forename: Stephen M
authors.identifier: http://orcid.org/0000-0001-8188-3092
authors.initials: SM
authors.lastname: Strittmatter
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D006801:Humans; D058225:Plaque, Amyloid / Q000378:metabolism*; D000072002:Prion Proteins / Q000378:metabolism; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D000072002:Prion Proteins; D011972:Receptor, Insulin