Innate immunity is associated with Alzheimer’s disease1, but the influence of immune activation on the production of amyloid-β is unknown2,3. Here we identify interferon-induced transmembrane protein 3 (IFITM3) as a γ-secretase modulatory protein, and establish a mechanism by which inflammation affects the generation of amyloid-β. 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 familial Alzheimer’s disease genes. Furthermore, knockout of IFITM3 reduces γ-secretase activity and the formation of amyloid plaques in a transgenic mouse model (5xFAD) of early amyloid deposition. 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 findings reveal a mechanism in which γ-secretase is modulated by neuroinflammation via IFITM3 and the risk of Alzheimer’s disease is thereby increased.
 

For original article, please see:https://www.nature.com/articles/s41586-020-2681-2

About TenNor Therapeutics

TenNor Therapeutics is a clinical-stage company specialized in the discovery and development of differentiated new drug products in diseases associated with bacterial infection and metabolism. TenNor possesses a unique multi-targeting drug conjugate technology platform and a strong new drug development pipeline with global IP protection. Several products are currently in late-stage of clinical development targeting H. pylori infection, implanted medical device infections, hepatic encephalopathy and irritable bowel syndrome with diarrhea. The company is committed to address the unmet needs in the disease area and provide safe and effective therapies for patients in China and around the world.

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