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It's No Longer a Theory - Inflammation is Proven to Grow Brain Plaques

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It's No Longer a Theory - Inflammation is Proven to Grow Brain Plaques about undefined
Beta amyloid plaques and tau tangles are well known hallmarks of Alzheimer's disease. But over the last decade, a third hallmark has emerged – a more significant one in my opinion: the presence of a sustained inflammatory immune response in the brain. The relentless activation of immune cells is linked to amyloid and tau plaque build-up, but scientists haven't been able to say whether this is a cause of Alzheimer’s disease or an effect. Now, a new study demonstrates for the first time that inflammation directly contributes to the production of beta amyloid plaques in the brains of Alzheimer’s sufferers. Let’s take a closer look at what this new discovery means to your memory health. In recent years scientists have become more focused on how the brain’s immune cells are involved in Alzheimer’s disease. This has led to findings that show beta amyloid proteins have antiviral and antimicrobial properties, suggesting they could develop in response to infectious agents and infection, which usually involve inflammation, and could contribute to the development of Alzheimer’s disease.

Growing Evidence for Neuroinflammation

Last December, studies showed that drugs designed to quell brain inflammation reverse dementia in mice. Three months earlier, another team of scientists discovered two genes that influence the risk for Alzheimer’s by their effect on the brain’s immune cells. Now, in a paper just published in the journal Nature, a large team of scientists led by Memorial Sloan Kettering Cancer Center, New York, confirmed that the immune system is involved, at least initially, in the process of brain plaque development. Researchers found that IFITM3, a protein involved in the immune response to pathogens, alters the activity of gamma-secretase, an enzyme that chops up precursor proteins into the fragments of beta amyloid that make up plaques. When the scientists removed IFITM3, the activity of the enzyme decreased, reducing the number of amyloid plaques that formed in a mouse model of Alzheimer’s disease. Senior author Yue-Ming Li explained, "We’ve known that the immune system plays a role in Alzheimer’s disease — for example, it helps to clean up beta amyloid plaques in the brain, but this is the first direct evidence that immune response contributes to the production of beta amyloid plaques — the defining feature of Alzheimer’s disease."

The Role of Infection and Inflammation

Believe it or not, the idea that an infection could be behind Alzheimer’s disease is not a new one. Three decades ago, a small number of Alzheimer's researchers proposed that pathogens like viruses or bacteria played a role in the disease. Not only did the idea not catch on in the scientific community, but it was strongly opposed for no clear scientific reason. The researchers had great trouble obtaining grants and getting their papers published. This is a familiar pattern in Big Medicine. People who prattle about “following the science” usually mean “follow the lead of the people who have the power and control the money.” This latest study puts pathogens firmly back on the Alzheimer’s treatment agenda and directly on the front lines as a possible cause of Alzheimer's, or at least a risk factor for the disease. That’s because the IFITM3 protein is only produced when invading viruses and bacteria trigger inflammation and activate an immune response.

Results Confirmed by Autopsy

To see if these findings were true in humans, Dr. Li and his colleagues looked at brain samples from people who died of Alzheimer's. They found that levels of IFITM3 correlated with levels of certain viral infections, as well as with gamma-secretase activity and beta-amyloid production. The researchers now plan to take their work one step further by investigating precisely how IFITM3 is involved with neuroinflammation, and whether the protein could act as a biomarker—or early warning sign— for Alzheimer's disease.
  1. https://www.mskcc.org/news/msk-study-links-inflammation-alzheimer-s-disease-development

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