Oligomer‐Aβ42 suppress glioma progression via potentiating phagocytosis of microglia

Abstract

AbstractAimsGlioma is characterized by an immunosuppressed environment and a poor prognosis. The accumulation of Amyloid β (Aβ) leads to an active environment during the early stages of Alzheimer's disease (AD). Aβ is also present in glioma tissues; however, the biological and translational implications of Aβ in glioma are elusive.MethodsImmunohistochemical (IHC) staining, Kaplan–Meier (KM) survival analysis and Cox regression analysis on a cohort of 79 patients from our institution were performed to investigate the association between Aβ and the malignancy of glioma. Subsequently, the potential of oligomer‐Aβ42 (OAβ42) to inhibit glioma growth was investigated in vivo and in vitro. Immunofluorescence staining and phagocytosis assays were performed to evaluate the activation of microglia. Finally, RNA‐seq was utilized to identify the predominant signaling involved in this process and in vitro studies were performed to validate them.ResultsA positive correlation between Aβ and a favorable prognosis was observed in glioma. Furthermore, OAβ42 suppressed glioma growth by enhancing the phagocytic activity of microglia. Insulin‐like growth factor 1 (IGF‐1) secreted by OAβ42‐activated microglia was essential in the engulfment process.ConclusionOur study proved an anti‐glioma effect of Aβ, and microglia could serve as a cellular target for treating glioma with OAβ42.