Rethinking the Cause of Alzheimer's
For the past 20 years both the focus of attention and hopes for treating Alzheimer's disease have centered on destroying or preventing fatty amyloid plaques in the brain. People with Alzheimer's tend to accumulate plaques in the brain, so it has always been assumed these were a major cause of dementia. As a result, a number of clinical trials were designed to target plaques. Results however have been universally disappointing. This, coupled with new information about the immune system, has led to some calls for a radical rethink on the cause of Azheimer's disease.
This week, the popular science journal New Scientist, published an article outlining why some researchers are calling for attention to move away from plaques and more towards cardiovascular health. A report published in the medical journal The Lancet (vol 372, p216) is typical of several pointing to a lack of progress with clinical trials on plaques. In this example, the brains of dead patients who had received a vaccine aimed at attacking amyloid plaques were examined. The vaccine had worked. Plaques were gone yet the symptoms of Alzheimer's had remained. Other disappointing results have been published and last year the company Myriad Genetics decided to pull the plug on a $200 million investment into plaque removal because of the lack of progress.
Not all the news has been bad. Another article in The Lancet (vol 372, p207) reported positive results from a clinical trial using dimebolin, a hayfever treatment. Patients scored higher in tests of cognitive abilities than those taking placebo. The body's inflammation processes are the of cause hay fever and this seems to correspond to the latest findings that suggest our immune system and vascular systems could well be the root cause of Alzheimer's disease.
Rapid decline in cognitive functions have previously been noted in people who have routine infections that trigger inflammation. Of interest is the fact that inflammation is rarely seen in the brain, but the rest of the body and the bloodstream are affected. In experiments with mice that show signs of inflammation and high concentrations of TNF-alpha (a substance secreted by white blood cells during inflammation) an accelerated Alzheimer's-like decline and death is seen.
People with Alzheimer's are more likely to have three gene variants. Most attention has focused upon one in particular that is responsible for the production of too much beta amyloid, the substance found in plaques. However, another of the gene variants called the clusterin gene, is not only responsible for cleaning the brain of beta amyloid but also for dampening down certain functions of the immune system. The third gene variant may cause too much fat to be drawn into brain cells, killing them.
So where do we stand? The exact role of amyloid plaques is still not understood so it seems likely that research will continue in its attempts to determine this. More research is likely into the relationship between the immune system, the way cells metabolize fat, and wear and tear on the circulatory system.
As to what we might do for ourselves an article in the Journal of the American Medical Association, vol 302, p 627 points the way in helping to prevent Alzheimer's. They report findings that people who eat a diet rich in fruit and vegetables and who are physically active reduce their risk of Alzheimer's disease by as much as 60 per cent.
Coghlan, A (2009) Radical Rethink on Alzheimer's. New Scientist. (September) p.6-7.