Comment on Beta-Amyloid
By Dr. Jack Diamond, Scientific Director, Alzheimer Society of Canada
Over the last few years it has become increasingly accepted that a small protein called beta amyloid (also known as A-beta) is the likeliest candidate to explain the degeneration of nerve cells that occurs in the brains of those with Alzheimer's disease. The individual A-beta molecules are produced in the nerve cells by enzymes which split them off a much larger protein (whose short name is "APP"). In the normal brain the A-beta does its job – which is still not determined exactly – then it's eliminated from the brain by special mechanisms designed to that end.
In the Alzheimer brain the A-beta molecules accumulate faster than they can be eliminated, and they then begin to stick together in twos and threes to form "oligomers". It has been established that it is the oligomers that are toxic to nerve cells, not the individual molecules nor the "plaques" which are produced as a final stage of their aggregating together.
What this new collaborative study by scientists at Harvard and in Ireland has discovered is that the toxic actions of A-beta appear to be entirely attributable to the A-beta "dimers" – i.e. the complex formed by the aggregation of just 2-molecules of A-beta. A single molecule or an aggregate of 3 A-beta molecules, or the fully-established plaques, are essentially non-toxic.
The study confirms too what has already been fairly well documented by other scientists, that the first victims of the toxic actions of A-beta are the junctions between nerve cells, the "synapses" - places where messages are transmitted from one cell to the next. But now it is clear that again, it is the A-beta dimers which are responsible.
What this means is that researchers can now focus specifically on the A-beta dimers as the appropriate target for therapy – perhaps by creating antibodies against them, as the present researchers did, or by using drugs designed to recognize and neutralize the A-beta dimers before they have time to exert their toxic actions. In general, the more accurately we can define the toxic agent which develops in the Alzheimer brain, the more accurately we can go about designing treatments against it. This is the most important message coming from these new investigations.
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