Jun 302010
 

As readers of this blog are probably aware, the prevailing theory of AD is that amyloid precursor protein is somehow aberrantly cleaved as it is secreted by neurons, and leads to the formation of beta-amyloid. Beta amyloid is a toxic “oligomer” or protein fragment that becomes improperly folded, and deposits into plaques. It is believed that the small oligomers of beta amyloid are more toxic than their larger aggregated counterparts (i.e.,amyloid fibrils), and in fact, the plaques may represent a way for the body to sequester such toxic oligomers.

In a recent paper, published in the Journal of Biological Chemistry*, Dr. Peter Tessier and his co-authors generated beta-amyloid peptides packed together in five unique isoforms, or “arrangements” (monomer, soluble oligomer, non-toxic oligomer, fibrillar intermediates and amyloid fibrils). In their experiments, three of these arrangements were toxic to human cells, two were not.

Next, the researchers introduced Resveratrol. The Resveratrol reacted with the toxic arrangements of beta amyloid, neutralizing their toxicity by inducing remodeling of their arrangement into non-toxic forms. It did not affect the non-toxic arrangements. Finally, Resveratrol seems to remodel the toxic species in a dose-dependent manner, which speaks to an underlying selectivity.

The ADCS is planning to begin a study of Resveratrol in mild to moderate AD in 2011, which should shed light on this interesting finding.

Michael Rafii, MD, PhD
Associate Medical Director, ADCS
This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

*Ladiwala et al, Resveratrol selectively remodels soluble oligomers and fibrils of amyloid a{beta} into off-pathway conformers. Journal of Biological Chemistry, May 2010.

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