Use of Vaccines for Treating Alzheimer's Disease – Results from UK Study
Comments by Dr. Jack Diamond, Scientific Director, Alzheimer Society of Canada
This new report from the UK describes the results of administering a vaccine designed to eliminate the tiny microscopic "plaques" that are scattered throughout the brain in Alzheimer patients.
For many years it has been assumed that these plaques, originally described by Dr Alzheimer 100 years ago, are responsible for the sickness and eventual death of nerve cells in the brain. The plaques are formed by the clumping together of thousands of molecules of a protein called (for short) Abeta. In the Alzheimer brain the Abeta molecules accumulate faster than they can be eliminated, and we now know that as they accumulate they begin to stick together, first in twos and later in threes or more. A recent exciting discovery was that it's when the Abeta molecules stick together in twos (forming "dimers") that they are toxic to nerve cells; when they are still single molecules and when they are stuck together in threes, the nerve cells are safe. This also means that the nerve cells are damaged long before enough Abeta molecules have come together to form plaques.
Now, the principle of a vaccine (i.e. of an immunization) therapy here is to get antibodies that will "recognize" Abeta molecules into the brain; the antibodies prevent the Abeta molecules from accumulating and sticking together. Ultimately the antibodies would cause a reduction in the plaque numbers, because plaques don't last forever, and if they're not renewed they'll gradually disappear.
In this new report they used a vaccine which stimulated the production of antibodies against Abeta, and yes – the total Abeta levels reduced, and eventually the plaque numbers reduced also. The disappointing finding, though, was that the dementia occurred normally in these patients. Nerve cells continued to degenerate, despite the apparent absence or at least profound reduction in Abeta and in plaques. Have we been wrong all these years, and it's not the Abeta that's causing nerve cells to die?
The report does, in fairness, acknowledge that the numbers of patients studied were small, and that there were minor differences in the findings between patients. Nevertheless the bottom line of the study is clear; we may need to revisit the assumption that Abeta is the main culprit in Alzheimer's disease.
However, what was not specifically measured were the levels of the Abeta "dimers" (the two-molecule aggregates). And this is now an absolute requirement before the "amyloid hypothesis" (the hypothesis that Abeta accumulation is the key event in Alzheimer's disease) can be abandoned. Conceivably the total Abeta levels and plaque numbers could be reduced while the specific levels of the Abeta dimers remained unchanged or even increased. We do need further research to answer this important question.
While the doubts remain, the final verdict is still on hold. Most researchers will not yet be prepared to write off vaccines as a viable treatment for Alzheimer's disease, especially while other, ongoing, vaccine trials are looking so promising.
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