Neuroinflammation links Alzheimer's disease and glioblastoma via shared molecular pathways

Neuroinflammation is a critical, yet distinctly impactful, feature in both Alzheimer's disease (AD) and glioblastoma (GBM). In AD, chronic activation of microglia and astrocytes by amyloid-β and tau drives neuronal injury and cognitive decline. Conversely, GBM tumor cells often hijack inflammatory pathways to foster an immunosuppressive microenvironment, supporting tumor growth and progression. Understanding the commonalities and divergences in these neuroinflammatory responses is crucial for identifying novel therapeutic targets and potentially repurposing existing drugs, addressing significant unmet needs in both devastating conditions.

This study was conducted as a narrative review, synthesizing existing literature on neuroinflammation in Alzheimer's disease and glioblastoma. Three reviewers performed a comprehensive PubMed search, including English-language articles such as original studies, reviews, meta-analyses, and experimental and clinical reports. Keywords encompassed neuroinflammation, microglia, astrocytes, inflammasomes, NLRP3, NF-κB, HIF-1α, cytokines, blood-brain barrier, and miRNAs. Due to the inherent heterogeneity of the included studies, the findings were synthesized descriptively rather than through quantitative meta-analysis.

The review identified substantial overlap in neuroinflammatory mechanisms between Alzheimer's disease and glioblastoma. Both conditions exhibit pronounced microglial and astrocytic activation, dysregulated cytokine signaling, and heightened inflammasome activity. Key shared mediators include IL-1β, TNF-α, NF-κB, HIF-1α, GSK-3β, and specific miRNAs. Furthermore, both diseases are characterized by blood-brain barrier dysfunction and hypoxia-related changes. In AD, these pathways primarily contribute to chronic inflammation, synaptic loss, and neurodegeneration, with NLRP3, NF-κB, and M1-like microglial polarization playing central roles. In GBM, however, these very same pathways are redirected to support tumor progression, angiogenesis, immune evasion, and therapy resistance, largely through the actions of tumor-associated macrophages and reactive astrocytes. > Despite sharing fundamental neuroinflammatory mechanisms, these processes lead to divergent outcomes: neurodegeneration in AD versus tumor support and progression in GBM.