Abstract
Alzheimers 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 β-amyloid peptide (Aβ). 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 Aβ oligomers. Recent evidence suggests that these oligomers are covalently crosslinked, possibly due to the interaction of Aβ 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 Aβ oligomers. An understanding of the chemical nature of Aβ is also required to elucidate the synaptotoxic process or processes in AD, which have so far resisted explanation.
Keywords: Beta-amyloid, Aβ, oligomer, covalent crosslinks, metal, neurotoxicity, synaptotoxicity
Current Alzheimer Research
Title: Is Covalently Crosslinked Aβ Responsible for Synaptotoxicity in Alzheimers Disease?
Volume: 5 Issue: 6
Author(s): R. Naylor, A. F. Hill and K. J. Barnham
Affiliation:
Keywords: Beta-amyloid, Aβ, oligomer, covalent crosslinks, metal, neurotoxicity, synaptotoxicity
Abstract: Alzheimers 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 β-amyloid peptide (Aβ). 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 Aβ oligomers. Recent evidence suggests that these oligomers are covalently crosslinked, possibly due to the interaction of Aβ 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 Aβ oligomers. An understanding of the chemical nature of Aβ is also required to elucidate the synaptotoxic process or processes in AD, which have so far resisted explanation.
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Cite this article as:
Naylor R., Hill F. A. and Barnham J. K., Is Covalently Crosslinked Aβ Responsible for Synaptotoxicity in Alzheimers Disease?, Current Alzheimer Research 2008; 5 (6) . https://dx.doi.org/10.2174/156720508786898433
DOI https://dx.doi.org/10.2174/156720508786898433 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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