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Amyloid Research May Impact Future Alzheimer's Medications

by Christine Kennard
for About.com

Updated: June 28, 2006

About.com Health's Disease and Condition content is reviewed by the Medical Review Board

Soluble beta amyloid kills brain cells rapidly

In Alzheimer's disease a protein fragment called beta amyloid, that would be broken down in a normal brain, begins to accumulate into tiny clusters known as plaques. These plaques exist between nerve cells in the brain and have the effect of destroying nerve tissue. It has been known for some time that the higher the levels of beta amyloid in the brain the greater the level of brain impairment.

Researchers at UC Irvine have discovered that amyloid toxicity is a complex mechanism that could suggest a need to modify treatment approaches. Most amyloid found in the brains of people with Alzheimer's is made up of long insoluble fibers, but another type of soluble beta amyloid, known as oligomers, may actually be more damaging.

Experiments have found that the soluble form of amyloid can lead to neuronal death in as little as 12 hours, whereas the insoluble form renders neurones useless over a few days, but does not actually kill the neurone. It is not yet known whether these are two distinct forms of beta amyloid or whether the soluble form becomes insoluble over time.

Professor Jorge Busciglio pointed out that any treatments designed to break down insoluble beta amyloid could actually speed up the process of neural degeneration, if amyloid becomes soluble in the process. In order to work out whether this could happen scientists now need to work out why soluble beta is so much more toxic. It is known, for example, that soluble beta affects an area of the nerve cell known as the mitochondria - which act like little power packs. If the mitochondria die, then so does the nerve cell.

Source: Atul Deshpande, Erene Mina, Charles Glabe, and Jorge Busciglio (2006) 'Different Conformations of Amyloid Induce Neurotoxicity by Distinct Mechanisms in Human Cortical Neurons'. Journal of Neuroscience. 26: 6011 - 6018

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