Is the amyloid hypothesis the right path to find a treatment for Alzheimer's disease?

There is both risk and reward in focusing Alzheimer's disease research on inhibiting amyloid production, according to a new article in Future Science OA . The article reviews the significant body of research proposing that the accumulation of beta amyloid in the brain is the Alzheimer's disease trigger that must be inhibited. Future Science OA is an online, open access, peer-reviewed title from Future Science Group.

Alzheimer's disease is the most common form of dementia in the elderly, affecting more than 36 million people worldwide, and no drugs have yet been proven to halt the progression of this degenerative disease. Significant research has focused on a theory known as the Amyloid Hypothesis, which suggests that the accumulation of a small protein fragment, beta amyloid or Aβ, within brain tissue is the event which triggers Alzheimer's disease. Aβ is a derivative of the longer Amyloid Precursor Protein (APP). The article reviews research efforts that have attempted to inhibit the generation of Aβ by modulating the secretase proteins that cut the APP into Aβ. The article reviews both the successes and failures of Aβ clinical trials, and the risks and rewards of continuing to pursue this line of research.

"This review outlines the role of the proteolytic secretases to produce beta amyloid peptide as part of the "Amyloid Hypothesis" of Alzheimer's disease," said the authors, of the Institute of Cardiovascular and Medical Sciences, University of Glasgow. "We examine the current status of the secretases as therapeutic targets in AD and speculate as to the viability of the AD hypothesis as a whole in light of recent findings."

"With the many failures we have seen in drugs targeting APP processing and the continued socioeconomic burden of Alzheimer's Disease, it is excellent to see such a comprehensive review covering research in the area and discussing potential ways forward," said Francesca Lake, Managing Editor.

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Future Science Group   press release

Publication

Ruth Macleod, Ellin-Kristina Hillert, Ryan T. Cameron & George S. Baillie. The role and therapeutic targeting of α-, β- and γ-secretase in Alzheimer's disease.   Future Science, Published Online April 14 2015. doi: 10.4155/fso.15.9