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Fighting Inflammation Can Boost Memory In Alzheimer’s

Posted on 3 March 2016

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An anti-cancer drug that inhibits the brain’s inflammatory response to plaques found in Alzheimer’s disease can enhance memory too

Inflammatory processes play an essential role in clearing the body of infection and protecting you everyday, but there is now plenty of evidence that inflammation has a dark side. This process is very hard to tune, and many diseases are worsened by an unhelpful, and even damaging immune response. Atherosclerosis for example, one of the biggest killers today, is made far worse by the inflammatory response and there is even evidence that inflammation can lead to increased cancer risk. New research adds Alzheimer’s to the list of disease where inflammation is a key therapeutic target.

A calming effect

As characteristic beta-amyloid plaques accumulate in Alzheimer’s disease, the brain’s defence system mounts a significant response – flooding the area with cells called microglia. Unfortunately this fails to clear problem, and experiments have indicated that increased inflammatory reaction by these microglia can actually worsen neuronal health.

“Our findings demonstrate the critical role that inflammation plays in Alzheimer’s-related memory and cognitive losses. While we were successful in removing the elevated microglia resulting from beta-amyloid, further research is required to better understand the link among beta-amyloid, inflammation and neurodegeneration in Alzheimer’s”

Microglia (green) surrounding neurons (red)

Microglia (green) surrounding neurons (red)

To test whether flushing some of these ‘angry’ cells could be neuroprotective, a team at the University of California treated mice with Alzheimer’s with a compound named pexidartinib, or PLX3397. This molecule is currently in a phase 3 cancer trial. Pexidartinib works by blocking receptors on the surface of microglia, which helps the cells proliferate and formulate an inflammatory response.

What happened?

When this drug was administered, the number of microglia was notably reduced, neuronal death declined, and memory and neuronal communication also improved. Microglia play a crucial role in brain housekeeping and ordinarily do more good than harm, but the research suggests in Alzheimer’s disease at least they contribute to disease progression.

It should be added that the drug does not remove the beta-amyloid plaques that have been so strongly linked to the disease, and would not be a ‘cure’ in any way. It may however improve memory and prove protective within a combination approach.

“Our work is telling us that these cells may contribute to the disease process, and targeting them with such specific drugs is a promising new approach”

Read more at Neuroscience News

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