Blocking inflammation restores cognition in a mouse model of Alzheimer's

By John Murphy, MDLinx
Published January 8, 2016

Key Takeaways

When scientists inhibited an inflammatory mechanism in a mouse model of Alzheimer’s disease, it helped improved memory and behavioral performance, and prevented synaptic degeneration in the mice. This finding adds to the evidence that inflammation plays a critical role in Alzheimer’s disease and that reducing inflammation can help halt disease progression, according to a study published online January 8, 2016 in the journal Brain.

Previous research already showed that an innate immune component is a factor in the onset and progression of Alzheimer’s disease. These researchers reported that an increase in immune microglial cells—a mechanism regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R)—coincides with neurodegeneration. Also, microglial proliferation increases in proximity to amyloid-beta plaques, another characteristic feature of Alzheimer’s disease.

In this study, the researchers investigated whether blocking CSF1R could reduce proliferation of microglia and, in turn, improve cognitive ability in mice with Alzheimer’s-like disease. The researchers gave the mice an oral tyrosine kinase inhibitor, which blocks CSF1R.

They found that treatment with the inhibitor not only reduced the number of microglial cells, but also switched the microglial cells’ inflammatory profile to an anti-inflammatory phenotype. In addition, the inhibitor preserved communication points between the nerve cells associated with Alzheimer’s. So, the treated mice performed better than the untreated mice in memory and behavioral tests.

“These findings are as close to evidence as we can get to show that this particular pathway is active in the development of Alzheimer’s disease,” said the study’s lead author Diego Gomez-Nicola, DPhil, MSc, Lecturer and Fellow in the Centre for Biological Sciences at the University of Southampton, in Southampton, UK.

Importantly, the researchers found that the treated mice retained a healthy number of microglial cells for normal immune function, which indicated that blocking CSF1R only reduced excess microglia.

What the research did not find was a corresponding reduction in the number of amyloid-beta plaques in the brain. This supports previous studies which argue that other factors may play a larger role in cognitive decline than amyloid-beta, the researchers wrote.

“The next step is to work closely with our partners in industry to find a safe and suitable drug that can be tested to see if it works in humans,” Dr. Gomez-Nicola said.

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