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Amyloid and Alzheimer's Disease: Inside and Out

Published online by Cambridge University Press:  02 December 2014

Joshua H. K. Tam  and
Stephen H. Pasternak
Joshua H. K. Tam
Affiliation:
J. Allyn Taylor Centre for Cell Biology, University of Western Ontario, London, Ontario, Canada Department of Physiology and Pharmacology, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada
Stephen H. Pasternak*
Affiliation:
J. Allyn Taylor Centre for Cell Biology, University of Western Ontario, London, Ontario, Canada Molecular Brain Research Group, Robarts Research Institute, Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada Department of Physiology and Pharmacology, Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada
*
Robarts Research Institute, 100 Perth Drive, London, Ontario, Canada, N6A 5K8. Email: spasternak@robarts.ca.
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Abstract

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Alzheimer's disease (AD) is poised to become the most serious healthcare issue of our generation. The leading theory of AD pathophysiology is the Amyloid Cascade Hypothesis, and clinical trials are now proceeding based on this hypothesis. Here, we review the original evidence for the Amyloid Hypothesis, which was originally focused on the extracellular deposition of beta amyloid peptides (Aβ) in large fibrillar aggregates, as well as how this theory has been extended in recent years to focus on highly toxic small soluble amyloid oligomers. We will also examine emerging evidence that Aβ may actually begin to accumulate intracellularly in lysosomes, and the role for intracellular Aβ and lysosomal dysfunction may play in AD pathophysiology. Finally, we will review the clinical implications of these findings.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 3 , May 2012 , pp. 286 - 298
Copyright
Copyright © The Canadian Journal of Neurological 2012

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