Title : Mapping the cytokine landscape in Alzheimer’s disease: A bibliometric analysis of global trends and emerging themes
Abstract:
Objective: Examine the global development of cytokine-related Alzheimer’s disease research through bibliometric analysis, identifying emerging themes and informing future therapeutic investigations.
Background: Alzheimer's Disease (AD) is the most common form of dementia, affecting 416 million individuals across the disease continuum. Dysregulated cytokine signaling plays a critical role in neuroinflammation in AD, with activated microglia serving as a major source of cytokines involved in disease progression. Despite increasing interest in neuroinflammation in AD, the evolution and emerging research themes within cytokine research have not been systematically evaluated, limiting understanding of the field’s trajectory.
Methods: In accordance with the Preliminary Guideline for Reporting Bibliometric Reviews of the Biomedical Literature (BIBLIO), the top 200 most cited research articles were extracted from the Web of Science Core Collection (WoSCC) using the keywords “Alzheimer's disease”, “cytokine”, and “neuroinflammation.” The extracted articles underwent a single-blind screening process based on predetermined eligibility criteria; records were systematically excluded if they: (1) merely mentioned cytokines without actively investigating them, (2) did not focus on an AD context, or (3) failed to explicitly report a relevant outcome, resulting in 100 included studies. Data was exported to RStudio/Biblioshiny and Microsoft Excel for bibliometric analysis and data visualization.
Results: 87% of publications were published between 2000 and 2023, with peak annual output occurring in 2000 and 2010 (n=7 each). Institutional affiliations were predominantly based in the United States (58.8%), followed by Italy (17.6%) and Germany (11.8%). Collaboration network analysis revealed the United States as the central global hub of international collaboration, demonstrating strongest cross-border research partnerships with China (n=6) and Germany (n=3). Senior author institutional affiliations and collaborations generally reflected countries with the highest AD prevalence per-capita in 2023; however, Japan, despite having the highest prevalence, was not represented. Titlebased frequency analysis showed greater representation of pro-inflammatory mediators, particularly IL-1 (n=17), IL-1β (n=13), and TNF-α (n=8). Thematic mapping evaluated research themes based on centrality and density. “Inflammation” emerged as a motor theme (highly developed and central), while “neuroinflammation” emerged as a relatively less developed and central theme. “Mouse model” surfaced as an emerging theme based on its low development and centrality metrics. A chronological analysis of topic trends over time further supported this finding, revealing conceptual evolution from foundational components (“protein,” “astrocytes,” and “microglia” in the mid-2000s) and peaking nodes (“inflammation” and “Alzheimer's disease” around 2010–2011) towards “mouse model” and “blood-brain-barrier” as the most recent introduced terms, indicating growing emphasis on translational approaches.
Conclusion: AD cytokine research has rapidly expanded over the past two decades, with inflammatory signaling remaining prominent and mouse-model research emerging as a developing direction. The relative underrepresentation of anti-inflammatory cytokines among highly cited publications highlights an underexplored area for future investigation into cytokine-mediated immune regulation and therapeutic strategies, while greater representation of Japanese institutions may improve geographic representativeness of future AD research.
