Feeds:
Posts
Comments

Posts Tagged ‘IFITM3’


Connecting the Immune Response to Amyloid-β Aggregation in Alzheimer’s Disease via IFITM3

Reporter : Irina Robu, PhD

Alzheimer’s disease is a complex condition and it begins with slow aggregation of amyloid-β deposits over the course of years. This produces a mild cognitive impairment and a state of chronic inflammation enough to trigger harmful aggregation of the altered tau protein. Clearing amyloid-β from the brain hasn’t produced telling benefits to patients suggesting that it is not the key process in the development of the condition.

Recent research indicates that beta-amyloid has antiviral and antimicrobial properties, indicating a possible link between the immune response against infections and development of Alzheimer’s disease. Scientists have discovered evidence that protein interferon-induced transmembrane protein 3 (IFITM3) is involved in immune response to pathogens and play a key role in the accumulation of beta amyloid in plaques. IFITM3 is able to alter the activity of gamma-secretase enzyme, which breaks down the precursor proteins into fragments of beta-amyloid that make up plaques. 

Yet it was determined that the production of IFITM3 starts in reply to activation of the immune system by invading viruses and bacteria. Indeed, researchers 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.

Innate immunity is also correlated with Alzheimer’s disease1, but the influence of immune activation on the production of amyloid beta is unknown. They were able to identify IFITM3 as γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-β.

According to the current research, inflammatory cytokines induce the expression of IFITM3 in neurons and astrocytes, which binds to γ-secretase and upregulates its activity, thereby increasing the production of amyloid-β. The expression of IFITM3 is increased with ageing and in mouse models that express Alzheimer’s disease genes. IFITM3 protein is upregulated in tissue samples from a subset of patients with late-onset Alzheimer’s disease that exhibit higher γ-secretase activity. The amount of IFITM3 in the γ-secretase complex has a strong and positive correlation with γ-secretase activity in samples from patients with late-onset Alzheimer’s disease. These conclusions disclose a mechanism in which γ-secretase is controlled by neuroinflammation via IFITM3 and the risk of Alzheimer’s disease is thus amplified

SOURCE

https://www.nature.com/articles/s41586-020-2681-2

Read Full Post »