Is Covalently Crosslinked Aβ Responsible for Synaptotoxicity in Alzheimers Disease? Academic Article uri icon


  • Alzheimer's disease (AD) is the most common form of dementia in the elderly, and is characterized by the deposition of extracellular amyloid plaques primarily composed of the beta-amyloid peptide (Abeta). While these plaques define the pathology of AD, disease progression has been shown to correlate more closely with the level of synaptotoxicity induced by soluble Abeta oligomers. Recent evidence suggests that these oligomers are covalently crosslinked, possibly due to the interaction of Abeta with redox-active metal ions. These findings offer new avenues for the treatment and prevention of disease, by modulating metal binding or preventing the formation of neurotoxic Abeta oligomers. An understanding of the chemical nature of Abeta is also required to elucidate the synaptotoxic process or processes in AD, which have so far resisted explanation.

publication date

  • December 1, 2008