A literature search was conducted on December 31, 2023, focusing on relevant publications from January 1, 2014, onwards. The search was performed using the Web of Science Core Collection database (WoSCC).¹ The search strategy was defined as follows: [topic search = (Exosomes OR Extracellular Vesicles) AND (multiple sclerosis OR amyotrophic lateral sclerosis OR Parkinson OR Alzheimer OR Huntington OR Neurodegenerative)]. Publications released before January 1, 2014, or not written in English were excluded from the results. To maintain the integrity of the research in this field, other types of articles were also excluded, such as meeting abstracts, editorial materials, letters, proceedings papers, corrections, early access articles, book chapters, news items, reprints, retracted publications, and retractions. This query yielded a total of 2,393 publications.

All data retrieved from the (WoSCC) were exported using various bibliometric analysis software for research purposes. VOSviewer was employed to analyze partnerships among countries, institutions, and authors of highly cited literature. It also creates a visual map of the network and clusters keywords with high co-occurrence frequency to identify research hotspots and trends. CiteSpace captures keywords with significant citation bursts, analyzes citations for journals and clusters, and visually maps all entries. Citation surges are a crucial indicator for identifying emerging trends in research within this field. Bibliometrix.org was utilized to construct a global distribution network of publications related to exosomes in neurodegenerative diseases (NDs).

After conducting a thorough search and assessment, a total of 2,393 publications met the inclusion criteria. This includes 1,488 articles and 905 review articles (Figure 1). Since 2014, the amount of research on exosomes in the field of neurodegenerative diseases (NDs) has steadily increased, peaking in 2023 with 304 articles and 116 review articles (Figures 2A,B). The total number of citations for these publications has also seen a yearly increase, reaching 18,911 in 2023, which includes 12,048 citations for articles and 7,287 for review articles (Figures 2C,D). When analyzing the number of publications and citations by country, the United States leads with 751 publications (501 articles and 250 review articles), followed by China with 365 publications (203 articles and 162 review articles) and Italy with 243 publications (142 articles and 101 review articles) (Figures 2E,F). Additionally, the United States has the highest number of citations, totaling 36,186 (including 24,538 for articles and 11,648 for review articles), while China follows with 14,020 citations (8,701 for articles and 5,319 for review articles). There are notable gaps in the publication and citation counts for other countries (Figures 2G,H). A global visualization map illustrates the depth of study for each country within this research area (Figure 2I).

Academic collaborations between different countries, institutions, and authors play a crucial role in facilitating knowledge exchange and expanding research on exosomes in neurological disorders (NDs). The geographic map in Figure 3A clearly illustrates the extensive cooperation among various countries, with China and the United States leading international partnerships. According to Figure 3B, China, the USA, and Italy rank as the top three countries engaging in collaborations with others. 47 institutions have published more than 15 papers each, as shown in Figure 3C. Notably, Nia, the University of San Francisco, Capital Medical University, Harvard Medical School, Zhejiang University, and Shanghai Jiao Tong University have each published over 34 papers, significantly contributing to research in this field (Table 1). The top 10 most productive authors in exosome research related to NDs from 2014 to 2023 are listed in Table 2. Kapogiannis and Dimitrios are identified as pivotal figures within the author cooperation network, having published the highest number of papers (Sato et al., 2011) and amassing a total of 3,921 citations (Figure 3D).

The topic categories of exosomes in neurodegenerative disease (ND) studies were analyzed across all relevant literature. Figure 4A presents a tree diagram illustrating the top 10 categories in the Web of Science (WOS), along with the number of corresponding articles. The top three categories account for over 70% of the total publications: Neurosciences with 775 papers (32.39%), Biochemistry and Molecular Biology with 504 papers (21.06%), and Cell Biology with 422 papers (17.63%).

An analysis of the 2,393 publications on exosomes in ND research revealed the most productive journals, which are listed in Table 3. After examining the subject categories, Figure 4B displays the top 10 journals based on local citations, with the numbers indicating the citation counts. The results show that the Journal of Biological Chemistry has the highest number of local citations, totaling 6,163. The second-ranked journal is PLoS ONE, with 5,154 local citations, followed by the Journal of Neuroscience, which has 4,110 citations. Renowned international journals such as Nature, Science, and Cell also rank highly in ND research.

Keywords can highlight the key areas and emerging trends in specific fields. A total of 60 keywords each appearing more than 20 times were selected for co-occurrence cluster analysis using VOSviewer. The 10 most frequent keywords identified were: Exosomes (581 occurrences), Extracellular vesicles (545 occurrences), Alzheimer’s disease (442 occurrences), Parkinson’s disease (255 occurrences), Exosome (237 occurrences), Biomarkers (182 occurrences), Neurodegeneration (170 occurrences), Multiple sclerosis (133 occurrences), Neurodegenerative diseases (114 occurrences), and Neuroinflammation (113 occurrences) (Table 4 and Figure 5A). Citespace was utilized for keyword clustering and timeline analysis

The analysis revealed the following top clusters: #0 Signaling pathway, #1 Exosome-like liposome, #2 Systemic sclerosis, #3 Emerging tool, #4 Neurodegenerative diseases, #5 Independent mechanism, #6 Polyglutamine diseases, #7 Therapeutic potential, #8 Systemic exosomal siRNA delivery, and #9 Amyloid beta. A timeline analysis showed that Exosome-like liposomes, Independent mechanisms, and Therapeutic potential have emerged as prominent research hotspots in recent years and are currently significant research directions (Figures 5B,C).

Burst analysis of keywords sheds light on the fastest-growing topics in recent years. As illustrated in Figure 5D, the intensity of the top 15 keywords experiencing an outbreak ranged from 5.6 to 8.2, with durations spanning from 3 to 4 years. Among these, transgenic mice exhibited the highest outbreak intensity, lasting for 5 years.

The analysis of 2,393 publications on exosomes in NDs research revealed the 10 most academically influential papers (Table 5). A co-citation relationship occurs when two or more papers are cited together in a single publication. By examining the bursts and clusters of co-cited references, CiteSpace can summarize the research directions among the referenced documents and identify common research themes.

Figure 6A displays the top 12 references with the most significant bursts in citation activity. Notably, a 2011 publication in Nature Biotechnology by Alvarez-Erviti et al. showed the highest explosive power with an intensity of 34.35 (Alvarez-Erviti et al., 2011b). The same year, another influential paper published in Neurobiology of Disease had an intensity of 27.89, underscoring the importance of Alvarez-Erviti et al.’s findings on exosomes in ND research and establishing a solid reference for future analyses (Alvarez-Erviti et al., 2011a). Additionally, a 2012 study by Saman et al. in the Journal of Biological Chemistry demonstrated strong explosive power, with an intensity of 23.90 (Saman et al., 2012). Other highly ranked publications also made significant contributions to the advancement of the field (Table 6) (Lachenal et al., 2011; Bellingham et al., 2012; Fitzner et al., 2011; Zhuang et al., 2011; Street et al., 2012; Vlassov et al., 2012; György et al., 2011; Baietti et al., 2012; Katsuda et al., 2013).

The analysis of the co-cited timeline view reveals the temporal relationships of hot topics by examining the co-cited references of the included papers. This method highlights research frontiers in the field. The timeline view of the top 10 key clusters is presented, and the results demonstrate significant clustering, indicated by a modularity value (Q) greater than 0.3 and an average contour value exceeding 0.7. In this context, the location of each occurrence corresponds to the time of its first citation, while a larger circle radius signifies a higher number of citations. This analysis suggests that the hot topics in exosome research concerning neurodegenerative diseases (NDs) are evolving. The identified clusters include: Astrocyte-derived exosomes (cluster #0), cholesterol-accumulated astrocytes (cluster #1), tunneling nanotubes (cluster #2), multiple sclerosis (cluster #3), Schwann cells (cluster #4), independent mechanisms (cluster #5), therapeutic loaded exosomes (cluster #6), GABA transmission (cluster #7), Parkinsonian disorders (cluster #8), mesenchymal stromal cells (cluster #9), and diagnostic biomarkers (cluster #10).

This analysis examines trending keyword topics from the last 10 years using R-bibliometrix. As illustrated in Figure 7A, the horizontal axis represents the year of occurrence, while the vertical axis indicates the frequency of keyword occurrences. The size of each node reflects how often a keyword appears, and the length of the horizontal line shows the duration of each keyword’s relevance. From 2013 to 2022, the keyword “extracellular vesicles” had the highest frequency, followed by “exosomes” and “brain.” Notably, “alpha-synuclein” garnered significant attention between 2018 and 2022. The latest trending themes regarding exosomes in neurodegenerative diseases (NDs) include outer-membrane vesicles, drug delivery systems, and convection-enhanced delivery.

Figure 7B presents a thematic map of exosome research in NDs. The relative position of each concept on the map indicates the development stage of the theme: (1) mature and essential themes are located in the upper middle region (e.g., stromal cells, in vitro studies, multiple sclerosis); (2) highly developed themes are found in the middle right region (e.g., exosomes, expression, brain); and (3) emerging themes are located in the lower right region (e.g., extracellular vesicles, Alzheimer’s disease, alpha-synuclein).

This bibliometric analysis revealed that the primary categories of exosome research in the field of neurodegenerative diseases (NDs) are Neurosciences, Biochemistry and Molecular Biology, and Cell Biology. Notably, the journal that published the most articles on this topic is the International Journal of Molecular Sciences, with a total of 131 articles and 3,347 citations, making it the top-ranked journal in terms of citations. Another significant journal in this field is Biochemistry and Molecular Biology.

Additionally, our separate analysis of articles and reviews found that, since 2021, while the total number of published articles has been steadily increasing, the number of published reviews has been declining. This trend suggests that current research on exosomes in the context of NDs is focusing more on new technologies and methods rather than on review analyses, indicating rapid development within this field.

In terms of international collaboration in NDs research related to exosomes, there is significant cooperation among different countries, institutions, and authors. China is the top country in cooperation and exchange with other countries and most of the publications cited are authored by Chinese. Academic cooperation between different countries can promote knowledge exchange and broaden the research horizon of exosomes in NDs, which also reflects China’s important position in this field of research. China and the United States have the most international cooperation. China, the United States and Italy are the top three countries that cooperate with other countries. Capital Med univ., Zhejiang univ., and Shanghai Jiao Tong univ. have all published more than 34 papers, making outstanding contributions to the research in this field. China has the largest number of academic scholars as leading and corresponding authors in all the countries, known as the great research society and community.

A standard research theme can be identified by analyzing the burst and clustering of co-cited references. In 2011, Alvarez-Erviti L et al. published two highly influential papers: one in Nature Biotechnology (intensity = 34.35) and the other in Neurobiology of Disease (intensity = 27.89). These papers demonstrate that exosomes, as explored by Alvarez-Erviti L, play a crucial role in the study of neurodegenerative diseases (NDs). Recent studies indicate that exosomes can influence NDs by regulating microRNA. Additionally, keyword cluster 8 suggests similar findings. Stromal cells, which are mentioned in the same co-cited references, rank highly on the topographic maps of exosomes studied in NDs, indicating their significant role in research within this area. As of 2023, the latest trend regarding exosomes in NDs focuses on drug delivery systems, highlighting the potential of exosomes to transport drugs. This aligns with future research directions exploring the use of exosomes for treating NDs. Furthermore, alpha-synuclein is a key cluster identified alongside the keyword trend theme and clustering of cited references, which may suggest a new research focus on exosomes in the context of NDs.

Co-occurrence analysis and burst analysis of keywords and co-cited documents are widely used methods for identifying research hotspots and predicting emerging research frontiers. In this study, we visually track the thematic evolution and prospects of exosomes in NDs research from multiple perspectives. Cluster analysis and thematic mapping indicate that stromal cells are a primary focus in this field (Figures 6B, 7B). The trending themes derived from the keywords suggest that siRNA delivery has gained significant attention in recent years (Figures 5B,C). Additionally, targeted drug delivery systems have emerged as the latest area of interest regarding exosomes in ND research, aligning with the current understanding of exosome delivery mechanisms. Overall, future research frontiers are likely to focus on the following areas:

This study is the first to use bibliometrics to systematically analyze research on exosomes in neurodegenerative diseases (NDs), providing comprehensive guidance for scholars in this field. In our study, we employed three widely used bibliometric tools simultaneously, which enhances the robustness of our data. Additionally, bibliometric analysis offers a broader perspective on current trends and cutting-edge developments compared to traditional reviews. However, this study has some limitations. First, our data were obtained solely from the Web of Science Core Collection (WoSCC) database, which may have resulted in the omission of relevant studies from other databases. Second, we only analyzed papers published in English, meaning that our findings might not represent the complete picture of research in this area. Lastly, due to the complexity of information technology and collaboration, bibliometric methods cannot fully distinguish the contributions of different authors or institutions.