Scientists discover Alzheimer's inhibitor

Phosphates responsible for the development of Alzheimer's

16.03.2012

Certain phosphates in Alzheimer's patients prevent regular breakdown of the so-called plaques in the brain and thus contribute to the development of the disease, report Bonn scientists in the journal „Journal of Biological Chemistry“ (JBC).

The researchers hope that their current understanding of Alzheimer's disease may help to develop new therapeutic approaches for Alzheimer's disease and help improve the diagnosis. In the brain of mice, the scientists have around the neurologist Prof. dr. Jochen Walter from the University of Bonn proved that the plaques of beta-amyloid peptides that trigger Alzheimer's can not be properly degraded due to the influence of certain phosphates. Thus, more and more peptides are deposited in the brain of those affected and Alzheimer's disease is taking its fatal course.

Phosphate group prevents the proper breakdown of Alzheimer's plaques
The researchers at the Department of Neurology and the Institute of Medical Microbiology, Immunology and Parasitology at the University of Bonn have, according to their own statements, succeeded in deciphering a previously unknown mechanism in the development of Alzheimer's disease. They investigated possible reasons for the increased deposition of plaques in the brains of Alzheimer's patients and came across a particular phosphate group that prevents proper degradation of the beta-amyloid peptides by the so-called microglial cells. From previous studies was already known that already „Years before the first Alzheimer's symptoms become noticeable“ become „plaques from incorrectly folded beta-amyloid peptides in the brain“ Professor Dr. Jochen Walter. According to the expert „these deposits the function of nerve cells in the brain“, which in the long run leads to the development of Alzheimer's disease.

Function of microglial cells in Alzheimer's patients disturbed by phosphates
To explain the increased deposition of the peptides in the brains of Alzheimer's patients, the researchers have in their recent studies, the function of microglial cells in the brain of mice examined more closely. Once the beta-amyloid peptides are deposited in the brain, „The microglial cells are activated and eat up some of the deposits again“, explained Professor Walter. However, in Alzheimer's disease, the mechanism for eliminating the peptides does not seem to work properly. The Bonn scientists have now discovered an explanation for this. Certain phosphate groups attached to the peptides prevent degradation by the microglial cells. This promotes the harmful deposition of beta-amyloid peptides in the brain and thus the development of Alzheimer's, write the Bonn scientists.

Hard to digest Alzheimer's plaque
Are bound to the beta-amyloid peptides corresponding phosphate groups, „then an insulin-degrading enzyme is blocked, which is of great importance for the activity of the microglial cells“, report Prof. Walter and colleagues. Beta-amyloid peptides with phosphate group are therefore for the microglial cells „much more digestible than without“, so the statement of the experts. It has been known for some time that s-insulin-degrading enzymes make a significant contribution to the breakdown of Alzheimer's plaque. New is however, „that the attachment of a phosphate group blocks this important decomposition process“, so the statement of Dr. also involved in the study Sathish Kumar. According to the expert, these can be „Now attribute effects to a single enzyme.“ About 20 to 30 percent of the peptides in Alzheimer's patients according to Bonn researchers have a phosphate group that protects them from degradation by the microglial cells.

Hope for early diagnosis and therapy in Alzheimer's
According to the researchers, the phosphate group has negative effects on Alzheimer's disease in several respects. On the one hand, the degradation of the beta-amyloid peptides is significantly reduced by the phosphate group, on the other hand, the phosphate promotes the clumping of the peptides and thus the formation of the plaques, explained Walter and colleagues. The nearly one million Alzheimer's patients currently living in Germany, although the current findings can offer no real help, but for the future, the researchers promise a lot. For example, specific antibodies could be developed that are targeted „bind to the beta-amyloid peptides with phosphate group and put the dangerous peptides out of action“, write the Bonn scientists.

Continue to develop new Alzheimer drugs
There may also be the option of using phosphate groups as biomarkers for the detection of early-stage Alzheimer's disease. „If there are many phosphate groups on the peptides, this would be an indication of an increased risk of Alzheimer's disease“, explained Prof. Walter and colleagues. Until appropriate diagnostic procedures or therapeutic approaches can be derived, be it „but still a very long way“, so the statement of the experts. The need for additional scientific work here can be seen not only from the countless studies that are currently underway on the subject, but also from the number of people affected. More than two-thirds of the 1.3 million dementia patients living in Germany today suffer from Alzheimer's, and by the year 2050, according to the Dementia Report 2011 of the Berlin Institute for Population and Development, the number of people affected is expected to double. (Fp)

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Picture: Gerd Altmann