Blocking Brain Inflammation in Alzheimer's Disease

Researchers have recently shown that suppressing inflammation in brain tissue reduces the symptoms of Alzheimer's disease in a mouse model, and does this without producing any impact on the amyloid build up associated with the condition. A range of past studies have provided evidence for the significant role of inflammation in the brain in the development of Alzheimer's disease. Portions of the specialized subdivision of the immune system in central nervous system tissue are vital to the support of nerve cells, not just involved in attacking pathogens. Consider the populations of microglia and astrocytes, for example, cell types for which the full list of roles remains to be cataloged. Thus dysregulation of the immune system, as is associated with rising levels of chronic inflammation, can have complex effects in the brain that are unlike those elsewhere in the body.

Blocking a receptor in the brain responsible for regulating immune cells could protect against the memory and behaviour changes seen in the progression of Alzheimer's disease. It was originally thought that Alzheimer's disease disturbs the brain's immune response, but this latest study adds to evidence that inflammation in the brain can in fact drive the development of the disease. The findings suggest that by reducing this inflammation, progression of the disease could be halted. The team hope the discovery will lead to an effective new treatment for the disease, for which there is currently no cure.

The researchers used tissue samples from healthy brains and those with Alzheimer's, both of the same age. The researchers counted the numbers of a particular type of immune cell, known as microglia, in the samples and found that these were more numerous in the brains with Alzheimer's disease. In addition, the activity of the molecules regulating the numbers of microglia correlated with the severity of the disease.

The researchers then studied these same immune cells in mice which had been bred to develop features of Alzheimer's. They wanted to find out whether blocking the receptor responsible for regulating microglia, known as CSF1R, could improve cognitive skills. They gave the mice oral doses of an inhibitor that blocks CSF1R and found that it could prevent the rise in microglia numbers seen in untreated mice as the disease progressed. In addition, the inhibitor prevented the loss of communication points between the nerve cells in the brain associated with Alzheimer's, and the treated mice demonstrated fewer memory and behavioural problems compared with the untreated mice.

Importantly, the team found the healthy number of microglia needed to maintain normal immune function in the brain was maintained, suggesting the blocking of CSF1R only reduces excess microglia. What the study did not find is a correlated reduction of the number of amyloid plaques in the brain, a characteristic feature of Alzheimer's disease. This supports previous studies that argue other factors may play more of a role in cognitive decline.



It is amazing how much of aging seems related to inflammation.

Posted by: Daniel Lemire at January 8th, 2016 8:49 AM

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