Aims: Glioma 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.
Methods: Immunohistochemical (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.
Results: A 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.
Conclusion: Our study proved an anti-glioma effect of Aβ, and microglia could serve as a cellular target for treating glioma with OAβ42.
Keywords: IGF-1; OAβ42; glioma; microglia; phagocytosis.
© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.