Inflammation and Beta-Amyloid Development Linked by Way of IFITM3

A research team at the Sloan Kettering Institute has discovered that IFITM3 plays a key role in the accumulation of beta-amyloid plaques—suggesting a possible link between the immune response against infections and the development of Alzheimer's disease.

"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," says Yue-Ming Li, contributing researcher. "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."

In their study—published in Nature—the team shows how IFITM3 alters the activity of gamma-secretase enzymes. They found that removing IFITM3 decreased the activity of the gamma-secretase enzyme and, as a result, reduced the number of amyloid plaques that formed in a mouse model of the disease.

Their findings suggest that viral and bacterial infections could increase the risk of Alzheimer's disease development. The team was able to demonstrate that IFITM3 in human brain samples correlated with levels of certain viral infections as well as with gamma-secretase activity and beta-amyloid production.

They also discovered that IFITM3 is increased in a subset of late-onset Alzheimer's patients, meaning that IFITM3 could potentially be used as a biomarker to identify a subset of patients who might benefit from therapies targeted against IFITM3.