Astrocytes and Alzheimer’s

Astrocytes are star shaped glial cells found in the brain and the spinal cord. An interesting article1 explains how these astrocytes could possibly prevent or provide a cure for Alzheimer’s. It is thought that these astrocytes make up a large percentage of the brain and have an important role supporting neurons to include clearing the beta-amyloid plaques associated with Alzheimer’s. It was recently shown that cells in the brains of people with Alzheimer’s “senesce.” This mechanism stops them from dividing and starts them on a path of destruction.

It is generally believed that cell senescence evolved to protect us from cancer. Cells can accumulate DNA damage as they age and they senesce to avoid incorrect division that can lead to cancer. The benefit of senescence over self-destruction is that it sends out a call to the immune system to destroy nearby cells that might also be affected. If the damaged cell is not killed, it goes on pumping out inflammatory proteins, which can cause damage thought to underlie age related ailments such as Alzheimer’s.

To provide some empirical data, brain slices were taken from cadavers. Slices were taken from fetuses, from people aged 35 to 50, and from people aged between 78 and 90.  The healthy brains from adults over 35 had six to eight times more senescent cells than those taken from fetuses. Cells from corpses who had had Alzheimer’s had more of these cells than their Alzheimer-free pairs of similar age. About 30 percent of the of the astrocytes seem to have senesced, a figure that was 10 percent higher in those with Alzheimer’s.

The theory is that the plaques and aging astrocytes get caught in a vicious cycle.  As the astrocytes senesce, they are less able to perform their plaque cleaning duties, and the accumulation of plaques drives more cells to senesce.2 If the astrocytes could be kept young, they could clear the plaque. The problem with preventing senescence is that it could increase the risk of cancer. Another approach is to get rid of the senescent cells. Research using mice has found that a technique for removing all of the senescent cells in a mouse prevented the onset of a range of age-related disorders. If this technique can be adapted for humans and the senescent cells can be cleared, then Alzheimer;s could probably be cleared.

Another approach might be to stop senescing brain cells from secreting their inflammatory brew. They have been found a compound that suppresses the secretions of senescent cells in the laboratory. That needs to be transitioned and tested with humans.

This work is quite promising. However, it should be remembered that beta-amyloid plaque might be a necessary condition, but it is not a sufficient condition for the onset of Alzheimer’s. There have been autopsies done of individuals whose brains were plagued by beta-amyloid plaque who had never shown any of the symptoms of Alzheimer’s when they were alive.

It is thought that keeping cognitively and physically active, and continuing to grow cognitively as we age builds up a cognitive reserve that resists or offsets these physical symptoms.

1Hamzelou, J. (2012). Why Alzheimer’s Hits Older Brains. New Scientist, 29 September, 6-7.

2Bhat, R., Crowe, E.P., Bitto, A. , Moh, M., Katsetos, C.D., Garcia, F.U., Johnson, F.B., Trojanski, J.Q., Sell, C., Torres, C. (2012). Astrocyte Senescence as a Component of Alzheimer;s Disease. PloS, doi.org/jdz.

© Douglas Griffith and healthymemory.wordpress.com, 2012. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Douglas Griffith and healthymemory.wordpress.com with appropriate and specific direction to the original content.

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