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.