 | Click the icon to see an image of amyloidosis. |
Other Proteins. Researchers have now identified other important proteins in the areas of the brain affected by Alzheimer's disease.
- ERAB (endoplasmic-reticulum associated binding protein) appears to combine with beta amyloid, which in turn attracts new beta amyloid from outside the cells. High amounts of ERAB may also enhance the nerve-destructive power of beta amyloid.
- AMY plaques resemble beta amyloid so closely that researchers were able to detect them only with the use of highly sophisticated techniques.
- Elevated levels of a protein called prostate apoptosis response-4 (Par-4) may cause nerve cells to self-destruct.
Oxidation and the Inflammatory Response
Researchers are also attempting to discover why beta amyloid is so toxic to nerve cells. Some researchers are focusing on two processes in the body that may be involved with Alzheimer's disease: oxidation and the inflammatory process. There is some evidence that such events can begin decades before Alzheimer's disease actually develops. One scenario for their role in Alzheimer's is as follows:
The Role of Oxidation.
- As beta amyloid breaks down it releases unstable chemicals called oxygen-free radicals. Once released, oxygen-free radicals bind to other molecules through a process called oxidation.
- Oxidation is the result of many common chemical processes in the body, but when oxidants are overproduced, they can cause severe damage in cells and tissue, including even affecting genetic material in cells (its DNA). Oxidation is known to play a role in many serious diseases, including coronary artery disease and cancers, and experts believe it may also contribute to Alzheimer's.
The Inflammatory Response.
- One result of oxidation is the marshaling of immune factors to repair the cellular injuries it produces. Overproduction of some of these factors, however, produces the so-called inflammatory response, in which the immune process itself can actually damage the body's own cells themselves.
- Principle immune cells in the brain are called macrophage/microglia (M phi). In the healthy brain, they play an important protective role against invading organisms. However, when they are activated by beta amyloid oxidation, they release toxic molecules called cytokines, which are known to cause harm. For example, significantly high levels of interleukin-6, a specific cytokine, have been detected in people with Alzheimer's.
- Other inflammatory factors of specific interest in Alzheimer's research are the enzyme cyclooxygenase (COX) and its products called prostaglandins. Excess amounts of these factors may increase levels of glutamate. Glutamate is an amino acid that excites nerves and, when overproduced, is a powerful nerve-cell killer.
- The inflammatory process has also been associated with the release of soluble toxins called amyloid beta derived diffusible ligands, which some investigators believe may prove to key players in the destructive process.
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