A recent paper (June 22nd from scientists from Harvard University and Trinity College, Dublin) has shown that the amyloid protein is most toxic to memory when it appears in a double form. The researchers extracted the amyloid protein (the small protein that has long thought to be the cause of Alzheimer’s) from the brains of Alzheimer’s disease victims and when the proteins were injected into rats, they noted that, depending on the specific form of amyloid, memory impairment occurred.
Alzheimer, himself, saw the accumulation of amyloid protein in what are now know as plaques, but these accumulations of amyloid represent many, many single amyloid molecules aggregated together.
The researchers found that this highly aggregated form of amyloid was not injurious to memory. However, when the amyloid protein occurred in just a doublet, (i.e., two molecules of amyloid stuck together) then it was in its most toxic form. Single amyloid (which we all produce for much of the time) was harmless to memory. These findings are important because the doublet form of amyloid is soluble and therefore can travel freely throughout the brain. These findings also suggest that the aggregated form that is visible to the eye under the microscope is not the most important form for researchers to prevent.
These findings are of particular interest to researchers at the Roskamp Institute, who showed in 1996 that soluble forms of amyloid could be toxic to blood vessels, increasing the likelihood that they would constrict. This is a particularly bad thing, especially after stroke, and it raised the possibility at that time that the soluble forms of Aß of amyloid might be more important than the aggregated forms.
These new findings also suggest that treatments aimed at lowering the amount of the amyloid doublet, might be those that are most effective in the disease. The new vaccine treatment, for instance, aimed at lowering the amount of amyloid by soaking up the amyloid with an antibody, might be effective at lowering these amyloid doublets. Other drugs that are coming on-line for the treatment of Alzheimer’s also targeted at the amyloid protein will now, no doubt, be examined to see whether they can lower the amount of the amyloid doublet.
Researchers at the Roskamp Institute are dedicated to finding new treatments and cures for Alzheimer’s disease. They were among the first in the world to show that the amyloid protein was most likely central to the disease process. This theory is now being tested in clinical studies throughout the world with exciting recent results suggesting that, indeed, the removal of amyloid might be an effective treatment for the disease (see recent reports on Elan Pharmaceuticals).