Genetic susceptibility of Alzheimer's disease associated with APOE polymorphism: systematic review and bibliometric study

Abstract

Introduction Alzheimer's disease is a progressive neurodegenerative disorder that is the leading cause of dementia worldwide. Genetic factors, particularly Apolipoprotein E (APOE) polymorphisms, are known to play a significant role in increasing susceptibility to Alzheimer's disease. The increasing number of publications related to APOE and Alzheimer's disease has prompted the need for bibliometric analysis and systematic reviews to comprehensively understand research developments and their genetic relationships. This study aims to analyze the global development of research on APOE polymorphisms in Alzheimer's disease through a bibliometric study and systematic review approach. Methods The study used a combined bibliometric and systematic review design. Data were obtained from the Scopus database for the period 2000–2025 using keywords Title-Abs-Key ((“APOE” Or “APOE E4” Or “Apolipoprotein E4”) And (“Alzheimer's disease”And (“Genetic Susceptibility”Or”Risk Factor”)) And (Limit-To (Doctype,”Ar”)) And (Limit-To(Language,”English”)) And Pubyear > 1999 And Pubyear < 2026. Bibliometric analysis was performed using VOSviewer and Microsoft Excel to evaluate publication trends, countries, institutions, journals, author collaborations, and co-occurrence keywords . A systematic review was conducted on 26 articles that met the inclusion criteria to evaluate the association of APOE polymorphisms with Alzheimer's risk. Results A total of 3824 articles from 718 publication sources were identified with an average citation of 51.51 per document. The United States was the country with the highest publication contribution. Keyword co-occurrence analysis showed that APOE4, genetics, and biomarkers were the main research themes. The results of the systematic review showed that APOE polymorphisms, especially rs429358 and rs7412, had a significant association with an increased risk of Alzheimer's disease in various ethnic populations with a very low p-value of up to 1E-320. Conclusion APOE polymorphisms play an important role in the genetic susceptibility of Alzheimer's disease and have the potential to be key biomarkers in early detection and the development of precision medicine in neurodegenerative diseases.