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Phosphorylated Amyloid-β: the Toxic Intermediate in Alzheimer’s Disease Neurodegeneration

  • Chapter
Alzheimer’s Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 38))

Abstract

Phosphorylated Amyloid-β (Aβ) was identified in Alzheimer’s disease (AD) brain. Using an anti-sense peptide approach the human cyclin-dependent kinase-1 (CDK-1) was identified as being responsible for Aβ phosphorylation. The phosphorylated Aβ peptide showed increased neurotoxicity and reduced ability to form Congo red-positive fibrils. Mutation of the serine 26 residue and inhibition of Aβ phosphorylation by the CDK-1 inhibitor olomoucine prevented Aβ toxicity, suggesting that the phosphorylated Aβ peptide represents a toxic intermediate. Cannabinoids prevented phosphorylated Aβ toxicity. The results from this study suggest that Aβ phosphorylation could play a role in AD pathology and represent a novel therapeutic target.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, Royal Free & University College Medical School, University College London, Rowland Hill Street, London, UK

    Nathaniel G. N. Milton

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  1. Nathaniel G. N. Milton
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Editors and Affiliations

  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. Institute of Biochemistry, University of Mainz, Mainz, Germany

    Falk Fahrenholz

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Milton, N.G.N. (2005). Phosphorylated Amyloid-β: the Toxic Intermediate in Alzheimer’s Disease Neurodegeneration. In: Harris, J.R., Fahrenholz, F. (eds) Alzheimer’s Disease. Subcellular Biochemistry, vol 38. Springer, Boston, MA . https://doi.org/10.1007/0-387-23226-5_20

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