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Brain Advance Access published online on September 29, 2006
Brain, doi:10.1093/brain/awl251
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 3, 2006
Revised August 15, 2006
Accepted August 16, 2006

Review Article

Alzheimer's centennial legacy: prospects for rational therapeutic intervention targeting the A{beta} amyloid pathway

Colin L. Masters 1 * and Konrad Beyreuther 2

1 Department of Pathology, The University of Melbourne and the Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
2 Centre for Molecular Biology, The University of Heidelberg, Heidelberg, Germany

* To whom correspondence should be addressed.
Colin L. Masters, E-mail: c.masters{at}unimelb.edu.au


  Abstract

It is now 100 years since the nosological definition of Alzheimer's disease emerged. In the first 80 years, very little progress was made in understanding the mechanisms that caused the brain to degenerate in a remarkably specific fashion (amyloid accumulation with neurofibrillary changes). Over the past 20 years, there has been an explosion of knowledge which continues today at an exponential rate. The molecular pathways underlying the synaptic dysfunction in Alzheimer's disease have delivered many validated therapeutic and diagnostic targets. A variety of therapeutic strategies aimed at disease modification are now in clinical development.

Keywords: A{beta} amyloid pathway; Alzheimer's disease; amyloid beta precursor protein.
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