The Innate Immune Protein IFITM3 as a γ-Secretase Modulatory Protein: From Inflammation to Alzheimer's Disease.

The mechanisms of Alzheimer's disease (AD) development are complex, and the detailed roles of neuroinflammation in AD still need to be elucidated. With various genetic and environmental risk factors, the accumulation of harmful amyloid plaques containing amyloid-β (Aβ) peptides is one of the main hallmarks of AD. Recent findings show that the innate immune protein interferon-induced transmembrane protein 3 (IFITM3) binds to γ-secretase and modulates Aβ production, providing a direct link between neuroinflammation, amyloidogenesis, and the pathogenesis of AD. In this review, we explore IFITM3-mediated modulation of γ-secretase complex activity and its pivotal role in AD pathology during neuroinflammation. Furthermore, we also provide an overview of the recent growing evidence connecting the roles of infection, the immune system, and AD pathogenesis.