Changing the activity of microglia will help with Alzheimer's disease

It is generally believed that memory loss in Alzheimer's disease is associated with the accumulation of toxic protein deposits in the brain tissue of patients – the so-called amyloid plaques. Earlier studies have shown that microglial cells are able to remove the beta-amyloid protein forming these plaques from the brain, and their activation, accordingly, can become a key component of successful treatment of this disease. However, the results presented in the doctoral dissertation Experimental Immunomodulation in Alzheimer's Disease by Lakshman Kumar Puli from the University of Eastern Finland indicate that the role of microglia in this case does not depend on its ability to eliminate beta-amyloid deposits from brain tissue.

Beta-amyloid deposits trigger the inflammatory process. Specialists still do not fully understand what role this inflammation plays – positive or negative. Inflammation can stimulate microglial cells, which in turn can disrupt the normal functioning of brain cells or even kill them. However, according to the results of the new work, blocking such a dangerous activation of microglia is possible even without removing beta-amyloid deposits from brain tissue.

In the course of the work, two different approaches were used to suppress the activation of microglia. One of them was the intravenous administration of polyclonal human immunoglobulins to genetically modified mice with Alzheimer's disease, which not only suppressed the activation of microglia, but also contributed to the survival of new neurons appearing in the hippocampus, a region of the brain considered responsible for memory.

Currently, immunoglobulins for intravenous administration are undergoing the final phase of clinical trials as a drug for the treatment of Alzheimer's disease. This technique has already demonstrated the ability to stop the progression of the disease (for a small number of patients, the period of stopping the progression of the disease was three years). The mechanisms of this positive action are unknown, but the results of a new experimental work indicate that they may be based on suppression of microglia activation and improved survival of newly emerging neurons in the brain.

The second approach was based on the creation of a new line of genetically modified mice that do not have the Nfkb1 gene responsible for the development of inflammatory processes in the brain. The removal of this gene significantly suppressed the activation of microglia, regardless of its ability to remove beta-amyloid from brain tissue. However, it is still unclear from the results obtained whether these inactivations have a good or bad effect on the state of the brain in the end. In any case, the results indicate that certain manipulations of microglia can have a positive effect on the condition of patients with Alzheimer's disease.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the AlphaGalileo Foundation:
Immune cells of the brain renew hopes for curing Alzheimer’s disease.

Portal "Eternal youth" http://vechnayamolodost.ru07.12.2012