The rise of mixed-pathology Alzheimer’s disease: A bibliometric analysis of α-synuclein, β-amyloid, and tau protein in neurodegenerative disease

Introduction Alzheimer’s disease (AD) involves key pathological proteins (β-amyloid, tau, and α-synuclein) increasingly studied to address disease complexity, yet their concurrent quantitative evolution remains unmapped. This bibliometric study characterizes global publication trends, authorship networks, and thematic shifts regarding concurrent triple protein investigations within cerebrospinal fluid (CSF)-related AD literature. Methods Global research trends were analyzed using Scopus data retrieved up to September 18, 2025 with terms for "alpha-synuclein", "beta-amyloid", "tau protein", "Alzheimer's Disease", and "cerebrospinal fluid", excluding reviews and animal studies. Network and thematic analyses utilized VOSviewer 1.6.20 and Biblioshiny (Bibliometrix R package). Results Analysis of 431 publications (2003–2025) revealed exponential growth since 2019. The United States of America (USA) led with 99 articles, Alzheimer's & Dementia was the top journal (33 articles). The most prolific author was Zetterberg HH (33 publications). Keywords clustered around neurodegenerative diseases and emerging biomarkers. Thematic evolution showed α-synuclein, β-amyloid, and tau protein as core themes transitioning to motor themes by 2024–2025. Discussion Output remained stable until 2019, followed by a rapid threefold increase. Thematic clustering reveals conceptual overlaps bridging classical AD markers, synucleinopathies, proteomics, and clinical endpoints, underscoring a shift toward mixed-pathology frameworks. Keyword networks demonstrate a contemporary scholarly focus on exploring multiplex and systemic markers. Conclusion The literature has evolved from isolated single-protein concepts to a dense, centralized track focusing on mixed-pathology terminology. Future research tracking should monitor how these multi-protein networks expand within broader cohorts to improve global geographic representation.