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Early Detection of Alzheimer's Disease May Involve Protein - A-beta-Star May Put Neurons to Sleep Not Kill Them - Treatment May Follow

March 16th 2006

Early Detection of Alzheimer's Disease May Involve Protein - A-beta-Star May Put Neurons to Sleep Not Kill Them - Treatment May Follow

Karen Ashe

Researchers at the University of Minnesota say they have identified a possible future target for therapies to defeat Alzheimer’s disease (AD) before it causes irreversible damage.  The identifying characteristic for AD is numerous insoluble clumps, or plaques, composed of a specific protein called amyloid-beta (A beta). 

Researchers had thought that these plaques caused AD, but they were mistaken.  According to Karen Ashe of the University of Minnesota, “About four years ago, we realized there was no correlation between the amount of plaque and the amount of memory dysfunction.”  This caused Ashe, a professor of neurology and neuroscience and director of the University's Center for Memory Research and Care, to start focusing on A-beta specifically.


The researchers notice abnormal brain scans of some people that were genetically predisposed to AD.  The abnormalities were very subtle but it did suggest changes in the way the brain operates long before nerve cells begin to die. Ashe chose one such mutant gene, which causes the brain to produce A beta in large quantities-a close approximation to the increased outputs of A beta that occur in normal aging.

One of Ashe’s postdoctoral lab fellows, Sylvain Lesne, noticed that these A beta molecules began to clump together in aggregates of three, six, nine or 12.  This led the team to investigate which clumps were most capable of causing memory problems.  It turned out the clumps of 12 A-beta molecules (A-beta_star) were the most potent in causing memory loss in rats. 


Interestingly these A beta molecules don’t seem to kill the neurons.  According to the researchers, the damage was not permanent.  After 10 days without injections of A-beta-star, the rats regained their memory. As Ashe puts it, the A beta protein, even A-beta-star, didn't kill neurons-it just put them to sleep.

The researchers have developed a blood test to detect A-beta-star.  They also plan to search for drugs that help AD patients by preventing the formation of A-beta-star that would eventually lead to an interference with neuron function.  Her work appears in the Journal Nature and will hopefully lead to a treatment for the 4.5 million Americans living with Alzheimer's disease, and the expected 14 million in the next 20 years.   

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