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

Incorporated in 2013, TenNor Therapeutics is a near-commercial stage biotechnology company dedicated to the discovery, development and commercialization of differentiated therapies to address unmet medical needs in disease areas associated with bacterial infections and bacterial metabolism. Empowered by its proprietary multi-targeting conjugate molecule technology, TenNor Therapeutics aims to deliver the best therapeutic solutions to overcome the limitations of conventional treatments and improve patient outcomes. As of July 24, 2025, TenNor Therapeutics had built a differentiated pipeline of seven innovative assets, including three Core Products, namely, rifasutenizol (TNP-2198), the world’s first and only new molecular entity (“NME”) drug candidate developed for the treatment of Helicobacter pylori (“H. pylori”) infection; rifaquizinone (TNP-2092) injection, a potential first-in-class, triple-targeting antibacterial drug candidate for the treatment of implant-associated bacterial infections; and TNP-2092 oral, the world’s first multi-targeting antibacterial drug candidate for the treatment of diseases associated with gut bacterial metabolism.

For more information, please visit: www.tennortherapeutics.com