Inflammation direct contributes to Alzheimer’s disease

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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.

In a new study, researchers found have 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.

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 research was conducted by chemical biologists at the Sloan Kettering Institute.

In the study, the team showed 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 the number of amyloid plaques that formed in a mouse model of the disease.

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.

This study is the first to provide a direct link between this inflammation and plaque development—by way of IFITM3.

The team found that the level of IFITM3 in human brain samples correlated with levels of certain viral infections as well as with gamma-secretase activity and beta-amyloid production.

Age is the number one risk factor for Alzheimer’s, and the levels of both inflammatory markers and IFITM3 increased with advancing age in mice, the researchers found.

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.

The researchers’ next plan is to explore IFITM3 as a biomarker for the disease and as a potential target for new drugs designed to treat it.

One author of the study is Yue-Ming Li, a chemical biologist at SKI.

The study is published in Nature.

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