Alzheimer’s disease is a neurodegenerative condition that is characterized by the buildup of clumps of beta-amyloid protein in the brain. Exactly what causes these clumps, known as plaques, and what role they play in disease progression is an active area of research important for developing prevention and treatment strategies.
Recent studies have found that beta-amyloid has antiviral and antimicrobial properties, suggesting a possible link between the immune response against infections and the development of Alzheimer’s disease.
Chemical biologists at the Sloan Kettering Institute have now discovered clear evidence of this link: A protein called IFITM3 that is involved in the immune response to pathogens also plays a key role in the accumulation of beta-amyloid in plaques.
“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, a chemical biologist at SKI. “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 a paper published September 2 in Nature, Dr. Li and his team show that IFITM3 alters the activity of an enzyme called gamma-secretase, which chops up precursor proteins into the fragments of beta-amyloid that make up plaques.
They found that removing IFITM3 decreased the activity of the gamma-secretase enzyme and, as a result, reduced that number of amyloid plaques that formed in a mouse model of the disease.
Mounting Evidence for a New Hypothesis
Neuroinflammation, or inflammation in the brain, has emerged as an important line of inquiry in Alzheimer’s disease research. Markers of inflammation, such as certain immune molecules called cytokines, are boosted in Alzheimer’s disease mouse models and in the brains of people with Alzheimer’s disease. Dr. Li’s study is the first to provide a direct link between this inflammation and plaque development — by way of IFITM3.