Sirtuins in Alzheimer's disease: Global research trends and bibliometric insights

The sirtuin (SIRT) family of NAD⁺-dependent deacetylases has emerged as a central regulator in Alzheimer's disease (AD)-related pathophysiological pathways. However, the global publication landscape, research hotspots, and translational implications of SIRT-related AD research remain insufficiently integrated.

Publications on sirtuins in AD was conducted in the Web of Science Core Collection database. Bibliometric analysis was performed using CiteSpace (version 6.4.1), VOSviewer (version 1.6.20), bibliometrix R package (https://www.bibliometrix.org), and Scimago Graphica (Version 1.0.46.0) to analyze trends, co-authorship, citation patterns, and research topics.

A total of 1141 publications from 62 countries were identified, with 71% being original research articles. The field showed sustained growth with notable acceleration after 2015. China led in publication output (357 articles, 31.3%), while the United States ranked first in total citations (22,190). The University of Barcelona and the University of California System were the most productive institutions. Co-authorship analysis identified 6019 authors with an average of 6.47 co-authors per document. Co-citation analysis emphasizes the central role of high-impact journals like Nature and PNAS. The thematic evolution in keyword analysis shows a shift from descriptive neurodegeneration studies toward mechanistic research, identifying oxidative stress, SIRT1/SIRT3 signaling, epigenetic regulation, amyloid-β, the mTOR pathway, autophagy, and neurogenesis as major hotspots. Biological interpretation of these hotspots suggests that SIRTs may contribute to AD pathophysiology through oxidative stress regulation, autophagy, epigenetic modulation, neurogenesis, and amyloid-β-related pathways, supporting their potential relevance to molecularly targeted strategies based on preclinical evidence. Citation burst analysis indicated emerging post-2015 interest in NAD⁺ metabolism and multi-target therapeutics, while persistent gaps remain in isoform-specific investigations, integrated multi-molecular studies, and robust clinical validation.

This study provides a comprehensive bibliometric and translational framework for SIRT-related AD research. Future research should prioritize mechanistic validation, address translational barriers including isoform selectivity and blood-brain barrier permeability, and expand investigation of under-studied SIRT isoforms.