The emerging role of oligodendrocytes in Alzheimer's disease: Integrating bibliometric insights with molecular pathogenesis

Introduction

Alzheimer's disease (AD), the most common neurodegenerative disorder globally, is characterized by core pathological features including amyloid-β (Aβ) plaque deposition, neurofibrillary tangles formed by hyperphosphorylated tau protein, and progressive neuronal loss. ¹ However, the traditional “neuron-centric” research paradigm has struggled to explain the complex pathogenesis of AD. Recent studies have revealed that central nervous system (CNS) glial cells, particularly oligodendrocyte, play a critical role in AD progression through maintaining myelin homeostasis, participating in neuroinflammation, and supporting axonal function. ² In addition to the neuronal loss characteristic of the disease, white matter degeneration and demyelination may be important pathophysiological features. Myelin loss and the inability of the OLs, the cells responsible for the production and maintenance of myelin, to repair myelin damage may be additional central features of AD. ³

Oligodendrocytes (OLs) are the sole myelinating cells in the CNS, and their dysfunction directly disrupts myelin integrity, leading to impaired nerve conduction, axonal energy crisis, and amplified neuroinflammation. ⁴ Concurrently, extracellular vesicles (EVs) act as “nanocarriers” mediating intercellular communication between OLs and other cells, while machine learning (ML) technologies enable novel insights into OL pathological mechanisms through multi-omics data integration. These findings underscore the importance of OLs in AD and suggest that preserving myelin integrity could serve as a therapeutic strategy. The central role of OLs in maintaining neuronal homeostasis positions them as critical contributors to AD progression and promising targets for innovative treatments. ⁵

Bibliometric analysis is a quantitative method used to assess research literature and provide insights into the development and influence of scientific fields. This approach includes a variety of tools and techniques for mapping science, such as network analysis and citation analysis, which help in visualizing knowledge trends and identifying key contributors within a field. Knowledge mapping, an integral aspect of bibliometric analysis, enables the exploration of relationships between different scientific concepts and research clusters, allowing researchers to visualize and understand the evolution of scientific knowledge, particularly in areas such as AD research, where a wide range of factors and mechanisms need to be comprehensively understood and linked together.^6,7 Such analyses help highlight emerging themes and influential works, providing an effective way to navigate the complex and ever-expanding body of research.

The objective of this study is to enhance our understanding of the involvement of OLs in AD. Specifically, we aim to examine the evolution of OL-related research in AD over the past decades through co-citation network analysis, thereby identifying key publications and emerging thematic trends. Furthermore, this work seeks to delineate the global research landscape by quantifying contributions from major entities such as countries, institutions, authors, and journals. Ultimately, the integrated bibliometric analysis aspires to reveal existing research gaps and potential opportunities, providing valuable insights to inform and direct future investigations in the field of AD.

Methods

Results

Study identification and characteristics

Figure 1A presents the total number of publications per year, with particularly rapid growth observed over the last decade. The trends in oligodendroglia research related to AD from 1981 to 2025 show a marked increase in both research output and citations, with an annual growth rate of 11.34% (Supplemental Table 4). The research area has experienced a steady growth in publications, with a notable increase beginning around 2010. This upward trend is corroborated by the cumulative citations, which exhibit a sharp ascent post-2016. Initially, the annual output was sporadic, with fewer than ten articles published each year until the mid-1990s. However, productivity then increased gradually, reaching a significant surge in the 2000s. This growth trajectory is mirrored in the citation metrics, which average 60.85 citations per document, underscoring the scholarly impact and the field's escalating influence (Supplemental Table 4). Most of the publications are original research studies, while a small portion are review articles, indicating a dominant focus on primary research in the field. Figure 1B shows the application of Price's Law to the growth of publications. The blue line represents the total number of publications per year, while the red dashed line is the exponential fit based on Price's Law. The model demonstrates a strong fit to the data, with a high coefficient of determination (R² = 0.9266), suggesting that the growth of oligodendroglia research in AD follows an exponential pattern typical of rapidly developing scientific fields.

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Figure 1.

Trends in publications, global collaboration and country involvement on oligodendroglia in Alzheimer's disease (1981–2025). (A) Total number of publications per year. (B) Price's Law Growth Curve. (C) World Collaboration Map. The lines connecting countries represent collaborative links between authors from different nations, with denser lines indicating higher collaboration intensity. Darker shades of blue highlight countries with substantial collaborative activity, particularly prominent in North America, Europe, and parts of Asia. (D) Top Contributing Countries by Document Count: The bar chart displays the number of publications by corresponding authors from various countries, distinguishing between single-country publications (SCP) and multiple-country publications (MCP).

Analysis of cooperation between institutions

Prominent institutions such as University of California Los Angeles, Harvard Medical School, Mayo Clinic, and University British Columbia exhibit substantial collaborative activities, as evidenced by their larger node sizes and thicker edges (Figure 2A). The University of California System published the most papers (n = 112), followed by Harvard University (n = 58), Mayo Clinic (n = 48) (Supplemental Table 6). Emerging institutions, such as Emory University, Rush University, and Chinese Academy of Sciences have also exhibited rapid growth in recent years. Figure 2B presents an institutional clustering analysis. The clusters surrounding University of California Los Angeles and Mayo Clinic denote a pronounced emphasis on interdisciplinary research within the biomedical sciences, whereas other clusters may reflect specialization in clinical medicine or targeted neurological research domains. These clusters provide crucial insights into how research institutions align their efforts within specialized networks to maximize collective expertise. Institutions such as Emory University, Rush University, and Columbia University are represented by red-colored nodes, signifying recent increases in collaborative activities and new publication outputs, indicative of proactive strategies to extend their research influence into emerging domains. Conversely, institutions represented by blue and green nodes, such as Mayo Clinic, exhibit well-established, long-term collaborations. These enduring ties suggest a focus on stability and depth, where institutions like Mayo Clinic maintain specialized research in specific medical domains rather than pursuing broad, interdisciplinary expansions. These evolving collaboration patterns reveal a diversified global research environment, wherein growth and stability coexist, thereby contributing to a richer and increasingly interconnected research ecosystem.

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Figure 2.

Collaboration, productivity analysis and author analysis of leading institutions in oligodendroglia Alzheimer's disease research. (A) Institutional Research Networks and Trends based on VOSviewer. (B) Institution's clustering analysis based on VOSviewer. Larger nodes represent institutions with more collaborations, and the different colors reflect distinct clusters of regional or institutional partnerships. (C) Co-authorship network. Each node represents an author, with the size of the node indicating the number of publications. The colors of the nodes correspond to different clusters of collaboration, suggesting a rich network of scholarly interactions among researchers. (D) The co-cited authorship network. The edges between nodes represent collaborative publications, with thicker lines indicating a higher number of joint works. The clustering of nodes reveals distinct research groups and collaborative relationships, with notable clusters identified by different colors.

Analysis of journals and co-journals

Supplemental Table 2 shows that Frontiers in Cellular Neuroscience is the most significant source, with 48 articles and the highest cumulative influence over time (local impact, with an h-index: 23). Other sources, such as Acta Neuropathologica, International Journal of Molecular Sciences, Journal of Neurochemistry, and Glia contribute substantially to the field, with 45, 45, 41, and 31 articles, respectively. Bradford's law is one of the basic laws of bibliometrics. It states that scientific journals in a certain field can be divided into core areas and subsequent partitions according to the number of publications, and the number of journals satisfies 1: n: n2. Based on this, we analyzed 24 core journals (Figure 3A,B). Among the journals in the core area of Bradford's law and the top five journals published above, more than half of the journals were in JCR Q1, indicating that the literature included in this analysis is of high quality (Supplemental Table 2), among which the highest impact factors were for Acta Neuropathologica (IF: 9.3, Q1). The steady growth in publication rate of these core journals reflects their enduring influence and increasing academic interest in this area, consistent with Bradford's Law. Figure 3D provides an analysis of the journal collaboration network, where Journal of Neuroscience appears as a key node, with its significant size denoting frequent collaboration with other impactful journals. Similarly, Nature and Proceedings of the National Academy of Sciences of the United States of America are notable for their substantial contributions and strong inter-journal linkages. Figure 3C presents the citation network analysis, again highlighting Frontiers in Cellular Neuroscience for its leading citation frequency, reflecting its pivotal role in shaping the discourse on oligodendroglia research in AD. International Journal of Molecular Sciences and Journal of Neurochemistry are also prominent, with their large nodes indicating substantial citation impact. The network's dense interlinkages reflect the interconnected nature of research in this domain, while other journals such as Glia and Neural Regeneration Research further illustrate diverse yet collaborative contributions.

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Figure 3.

Key journals contributing to oligodendroglia research in Alzheimer's disease. (A) Core Journals Identified by Bradford's Law. (B) Top 5 Journals Over Time. The line graph depicts the cumulative occurrence of articles from key sources over time. The y-axis shows the number of publications, while the x-axis represents the publication year, ranging from 1981 to 2025. (C) Journal Citation Network Visualization by Time. (D) Journal Citation Network Visualization. Each node denotes a journal, while the connecting lines represent citation relationships. The color gradient reflects temporal variations in citation relevance across years. Node size indicates citation frequency, while colors denote clusters of journals that frequently cite one another.

Analysis of references and documents

The citation network, as seen in the CiteSpace visualization (Figure 4A), clusters primarily around research topics such as hippocampus, AD, and vascular dementia. These topics exhibit significant relevance within the regional context, where local citation counts serve as a proxy for specific academic interests. This interconnected network underscores the collaborative nature of the field and the crucial influence these works have had in shaping the ongoing directions of Oligodendroglia in AD research. Figure 4B shows the Top 25 References with the Strongest Citation Bursts. In the field of research, the characteristics of citation bursts in the literature can effectively reveal the evolution of research hotspots and the spread of the influence of key achievements. Since 2014, the research enthusiasm has increased significantly. The correlation between citation burst strength and duration shows that: early foundational literatures maintain long-term low-intensity citations due to their theoretical, the superposition of mid-term technology-driven factors (such as single-cell sequencing) and disease demands (such as AD) gives rise to high-intensity, medium-cycle hotspots; and recent research on mechanism deepening continues to exert influence due to its potential for clinical translation.

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Figure 4.

Analysis of oligodendroglia in Alzheimer's disease references. (A) Keyword Clustering based on References. (B) Top 25 References with Strongest Citation Bursts in Alzheimer's Disease Research. The burst timeline (right-hand side) shows the periods during which these bursts occurred, with red segments indicating the time intervals when each reference received heightened attention. The burst detection process highlights key works that had a significant impact in a short time, suggesting pivotal contributions to the evolving research landscape in Alzheimer's disease.

The dataset comprises 1780 documents with 131,698 references, reflecting the extensive body of research on the role of OLs in AD from 1981 to 2025. On average, the retrieved publications were 8.58 years old and received 60.85 citations per document, reflecting the substantial academic influence and enduring relevance of research in this field (Supplemental Table 4). In Supplemental Table 3, the most locally cited publications are those by Desai MK (2009) ⁹ and Nasrabady SE (2018), ³ with 67 and 70 local citations, respectively. These influential studies have been instrumental in advancing our understanding of the role of OLs and myelin integrity in the pathogenesis of AD. Desai MK demonstrated that in triple-transgenic AD (3xTg-AD) mice, region-specific alterations in myelination and OL marker expression occur before the onset of amyloid and tau pathology, suggesting that OL dysfunction is an early event in AD progression. In parallel, Nasrabady SE proposed that myelin breakdown and white matter degeneration are fundamental contributors to cognitive decline in AD, positioning OLs as critical mediators between neuronal pathology and neurodegeneration. Collectively, these findings have shifted the conceptual framework of AD from a neuron-centric disorder to one in which oligodendrocyte impairment and myelin loss play central mechanistic roles, offering new perspectives for early intervention and therapeutic targeting.

Keyword analysis

The keywords represent the focus of a study. Analyzing keywords can identify the hotspots and trends of research in the field. Our study includes 11,747 “Keywords Plus” and 3755 author keywords, underscoring the breadth of topics and themes explored within this research domain. Figure 5A presents a heatmap illustrating keyword density. The frequency analysis of Keywords Plus, author keywords, and all keywords was performed and presented in the form of a word cloud (Figure 5B). Excluding the search terms, the top five keywords can be roughly divided into AD, human, and oligodendroglia. Among them, the number of occurrences of “microbiota” was the highest, and the frequencies of “microglia” and “astrocyte” were also high. The keywords were clustered in VOSviewer to verify the above categories. Figure 5C and Figure 5D depict knowledge mapping networks related to neurodegenerative diseases. In Figure 5C, keywords such as “Alzheimer's disease”, “neurodegeneration”, “oligodendrocyte”, and “microglia” are prominently displayed, with clear connections among them, reflecting the research focus and interrelationships in this field from 1981 to 2025. From 2018 onwards, “exosomes” “extracellular vesicles” “white matter injury” “oligodendrocyte precursor cell” “neurodegeneration” “myelination” “microglia” gradually attracted attention. Figure 5D further visualizes the collaborative and associative relationships between these keywords through a more colorful and complex network structure, indicating the multi-faceted and intersecting nature of research on neurodegenerative diseases, involving multiple aspects like different cell types, disease entities, and research techniques. These two figures collectively show the research hotspots and the evolving trend of connections among relevant topics in the field of neurodegenerative diseases over a certain period. Figure 5E is a Trend Topics Analysis Graph, which is used to display the changing trends of the attention paid to different research topics during the period from 1981 to 2025. Looking at the overall trend in the graph, the higher up a term is, the more significant the rise in its popularity in the later period. Since 2020, there has been a growing focus on the ML association with AD alongside other areas such as neuroinflammation and OLs, marking it as a hot topic in the literature. In addition, the related research on electron microscopy has continued from 1994 to the present, revealing that electron microscopy and immunohistochemistry are the main means to study AD.

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Figure 5.

Keyword analysis of oligodendrocyte in Alzheimer's disease. (A) Heatmap of Keyword Density. (B) Author Keyword Clouds. (C) Network of Co-Occurring Keywords by Time. Nodes represent keywords, node size represents the frequency of keyword occurrence, and the larger the node, the more keywords appear; The connection between nodes represents the connection between keywords, and the more connections, the closer the connection. The color change of the node is consistent with the timeline change color below. (D) Co-occurrence Network of Keywords. (E) Trend Topics Over Time.

Discussion

The incidence and prevalence of AD have increased significantly worldwide, leading to a considerable medical and social burden. ¹⁰ Currently, clinical treatment for AD mainly aims at alleviating symptoms after their onset. The primary therapeutic options include cholinesterase inhibitors, NMDA receptor antagonists, and newer medications aimed at reducing amyloid plaques or tau protein aggregation. ¹¹ However, available treatments can only slow disease progression and do not offer a cure, including specific therapies targeting Aβ and tau proteins. As such, attention to other molecular mechanisms presents new opportunities for advancing understanding. In this context, our research is centered on the role of OLs in AD, which may provide novel insights and therapeutic targets for the onset, progression, and treatment of this neurodegenerative disorder.

According to Figure 1, the development of research in this field can be divided into two main phases. The initial phase, from 1981 to the early 2000s, saw relatively slow growth, with sporadic publications and limited focus on OLs in AD. The second phase, beginning in the 2010s, marks a period of significant growth characterized by an increased number of studies investigating OL dysfunction, neuroinflammation, and the integrity of myelin. This surge is evidenced by the prominence of keywords such as “oligodendrocyte”, “neuroinflammation”, and “myelin” in recent publications. These trends are consistent with an expanding body of literature suggesting close associations between oligodendrocyte dysfunction, altered myelination states, and hallmark pathological features of AD, including Aβ deposition and tau-related pathology, particularly in experimental and model-based studies. In support of this association, Torii et al. reported tau expression in mature, actively myelinating oligodendrocytes, emerging later than conventional myelination markers and thereby indicating tau as a potential marker of advanced OL maturation rather than a primary causal driver. ¹² In parallel, AD–associated pathology has been shown to coincide with disrupted oligodendrocyte precursor cell activity and reduced oligodendrocyte-driven myelin formation, alterations frequently observed alongside axonal damage and core AD pathological features involving both Aβ and tau. ⁵ Through a comprehensive analysis of the evolution and frequency of keywords in the literature included in this study, we identified several prominent keywords such as “oligodendrocytes”, “Alzheimer's disease”, “neuroinflammation”, “myelin”, “microglia”, “glial cells”, “Aβ”, “tau pathology”, “cognitive impairment”, “neurodegeneration”, and “astrocytes” among others. Based on the clustering analysis conducted using various bibliometric tools, the focus of these studies was largely centered on understanding the role of OLs and their impact on AD pathogenesis.

Specifically, the keywords indicated a growing interest in exploring the relationship between glial cell function and the underlying molecular mechanisms of AD, such as the contributions of “neuroinflammation,” “myelin health,” and “oligodendrocyte progenitor cells” to disease progression. Initially, in the earlier stages of research, keywords such as “Aβ”, “tau protein”, and “neurofibrillary tangles” dominated the literature, reflecting a strong focus on the classic pathological features of AD. This focus highlighted the attempts of researchers to elucidate the mechanisms behind the abnormal protein accumulations central to AD, which have long been established as the hallmarks of the disease. During this foundational phase, the identification of these key pathological processes laid the groundwork for subsequent research into the more nuanced aspects of neurodegeneration. As research progressed into the mid-2000s, new concepts began to emerge, which shifted the focus towards understanding cellular dynamics and interactions within the CNS. Terms like “neuroinflammation”, “oxidative stress”, and “oligodendrocytes” started to appear frequently, indicating a broadened scope of research interest. This shift suggested an increasing awareness of the critical role that support cells such as OLs play in maintaining neuronal health and how their dysfunction may contribute to AD progression. This period also saw a growing recognition of the importance of OLs and myelin health, underlined by the frequent appearance of related keywords, emphasizing the broader impact of glial cell dysfunction. In recent years, the focus of research has notably evolved towards a deeper exploration of cellular and molecular interactions, particularly with an emphasis on “neuroinflammation” and “glial cell dysfunction.” Emerging keywords such as “oligodendrocyte progenitor cells” and “reactive astrocytes” indicate that current research is actively probing into the roles of different types of glial cells in AD and their potential as therapeutic targets. It is worth noting that “microbiota” appears most frequently in the literature, yet it is mainly concentrated in recent studies, likely reflecting the emerging interest in the gut-brain axis in AD research. In addition, the related research on electron microscopy has continued from 1994 to the present, revealing that electron microscopy and immunohistochemistry are the main means to study AD.

Glial cells, including OLs, astrocytes, and microglia, play a crucial role in the neuroinflammatory processes of AD. ¹³ The accumulation of Aβ plaques and tau tangles triggers a cascade of inflammatory responses, primarily involving the activation of microglia and astrocytes, which further exacerbates neurodegeneration. This chronic neuroinflammatory state is a significant driver of AD progression, impacting multiple aspects of disease pathology. ² In recent years, the role of OLs has also gained increased attention. OLs are responsible for forming myelin, which is essential for fast neuronal signaling and brain function. Disruption of oligodendrocytes and myelin results in axonal damage and neurodegeneration, key features of AD. White matter abnormalities and myelin alterations have been repeatedly reported in both human studies and experimental models of AD and are increasingly discussed as potential early or accompanying features of disease progression, although their precise temporal relationship with classical neuronal pathology remains context-dependent. The underlying causes of myelin loss in AD include oxidative stress, neuroinflammation, and excitotoxicity, which are linked to the accumulation of Aβ and tau hyperphosphorylation. Tau pathology is a defining feature of AD, with tau positron emission tomography (PET) scans playing a crucial role in confirming diagnoses. ¹⁴ Tau, a neuronal protein, is essential for microtubule assembly and axonal transport. Under normal conditions, tau helps stabilize microtubules, promoting proper cellular function. However, mutations associated with tau pathology disrupt its ability to bind to microtubules, leading to the protein's self-aggregation. This misfolded tau forms tangles within neurons, a hallmark of tauopathies such as AD. Interestingly, tau is also expressed in OLs, where it is involved in crucial developmental processes, including OL maturation and myelin synthesis. However, tau aggregation in these cells impairs both their maturation and the production of myelin. Tau aggregates have been detected in OLs across various tau-related diseases, highlighting the broader impact of tau pathology beyond neurons. ¹⁵ Recent studies have further shown that tau can propagate within the white matter of the brain, particularly within the corpus callosum. After unilateral inoculation of tau, the protein spreads from the inoculated side to the contralateral side of the corpus callosum, with significant evidence of tau phosphorylation. This suggests that tau pathology not only disrupts neuronal function but also contributes to the seeding and propagation of tau aggregates in OLs, potentially exacerbating the damage to white matter. ¹⁶

The study has shown that OLs are implicated in AD as a source of Aβ, which negatively impacts neuronal function.^17,18 Aβ pathology has been reported to disrupt oligodendrocyte precursor cell differentiation and induce cellular senescence, changes that are associated with enhanced neuroinflammatory responses and reduced remyelination capacity. ¹⁹ Recent experimental studies suggest that oligodendrocytes may contribute to Aβ-related pathology under specific conditions; however, these findings are largely derived from animal models and should not be interpreted as evidence of a universal or primary causal role of OLs in human AD. In addition, Aβ has been shown to interfere with oligodendrocyte function and myelin homeostasis by inducing dysregulation of hnRNP A2, leading to altered RNA metabolism and myelin protein synthesis. Such molecular disruptions are increasingly recognized as part of the complex pathological landscape of AD rather than as singular drivers of disease onset or progression. ²⁰ Neuroinflammation further exacerbates the condition by influencing OLs, leading to demyelination and compromised myelin integrity. ²¹ Emerging studies suggest that microbiota-related mechanisms, including short-chain fatty acids, immune modulation, and neuroinflammatory pathways, may be associated with oligodendrocyte function and myelin-related processes in AD. ²² Despite these negative effects, OLs also play a regulatory role in neuroinflammation, revealing a complex and bidirectional interaction between these cells and inflammatory processes. ²³ Thus, the interplay between OLs, neuroinflammation, and AD is multifaceted, contributing both to disease progression and to potential intervention strategies.

Microglia, the resident immune cells of the CNS, are critical for brain health, serving to clear cellular debris and modulate inflammation. In AD, microglial activation is induced by amyloid pathology, which amplifies neuroinflammation. Dysregulated microglial activity exacerbates AD by promoting chronic inflammation, which, in turn, negatively impacts OLs and neuronal survival. Interestingly, deleting BACE1 in OLs not only reduces amyloid plaques but also increases the presence of microglia around these plaques, suggesting a complex interaction between these two glial cell types. ²⁴ Furthermore, microglia support OLs function by promoting differentiation and enhancing myelin debris clearance, although chronic activation can have detrimental effects, such as increased neuronal apoptosis and impaired myelination.^25,26 Astrocytes play a pivotal role in the pathogenesis of AD. They are activated by Aβ and phosphorylated tau, triggering neuroinflammation and the release of neurotoxic substances that exacerbate the progression of AD.^27,28 As part of this response, astrocytes undergo significant metabolic changes, including the upregulation of proteins like mesencephalic astrocyte-derived neurotrophic factor, which is linked to synaptic dysfunction and cognitive deficits.^29,30 Astrocytes also interact with OLs, promoting their development and myelination through signaling pathways such as ephrin-B1. However, astrocytes can also exert detrimental effects on OLs. For example, in conditions like multiple sclerosis, astrocyte activation is associated with reduced OL viability and impaired myelination. ³¹ In summary, the interactions between glial cells—including OLs, microglia, and astrocytes—and AD pathology are complex and multifaceted. Each cell type exerts both protective and detrimental influences, affecting neuroinflammation, amyloid plaque formation, and tau pathology, which collectively contribute to AD progression.

Research into remyelination therapies represents a potentially promising therapeutic direction for AD, focusing on countering oligodendroglial dysfunction and promoting myelin repair to mitigate cognitive decline. In AD, oligodendroglial impairment, driven by factors such as Aβ-related disruption of myelin homeostasis and RNA metabolism, compromises myelin protein synthesis and calcium regulation, contributing to demyelination and synaptic vulnerability. ²⁰ Therapeutic strategies such as low-intensity transcranial ultrasound, Liver X Receptor activation, and agents like ospemifene and erythropoietin have shown beneficial effects on oligodendrocyte differentiation and remyelination in preclinical models, with reported associations with cognitive improvement.^32–35 However, further validation in clinical settings is required to determine their translational relevance. Furthermore, molecules like microRNA-219 link remyelination processes directly to AD pathophysiology by modulating tau toxicity. ³⁶

The development of such targeted remyelination therapies increasingly benefits from integration with ML, which provides powerful capabilities for decoding AD heterogeneity and optimizing intervention strategies. ML models can identify oligodendroglia-related genes and molecular networks associated with AD, offering insights into diagnostic biomarkers and immune interactions. ³⁷ Recent magnetic resonance imaging (MRI)-based studies use myelin-related metrics (e.g., T1w/T2w ratio, in-vivo g-ratio mapping) as interpretable features to quantify white-matter demyelination and support early diagnosis. ³⁸ Machine learning–driven multi-omics frameworks that combine single-cell and spatial transcriptomic data have delineated multiple disease-associated oligodendrocyte (DAO) subpopulations linked to cognitive deterioration and pathological variability. ¹⁹ Subsequent single-cell RNA sequencing analyses validated the presence of these oligodendrocyte states and further subdivided them into transcriptionally distinct groups. ³⁹ Spatial enrichment of DAO signatures has been reported in demyelinated lesions and axonally compromised regions in mouse models of both multiple sclerosis and AD, indicating that this phenotype may represent a conserved response to CNS injury rather than pathology-specific mechanisms such as amyloid or tau accumulation. ⁴⁰ In line with this view, DAO-like cells preferentially localize near Aβ plaques and show increased expression of AD-associated risk genes, including C4b and ApoE. ⁴¹ Moreover, SERPINA3N expression has been detected in post-mortem AD brain tissue, and DAO presence is prominent in peri-plaque areas, supporting the relevance of oligodendrocyte-associated pathways as potential therapeutic targets. ⁴² Importantly, accumulating evidence indicates that DAO-like phenotypes may represent a conserved glial response to CNS injury rather than a pathology-specific mechanism restricted to AD, underscoring the need for cautious interpretation when extrapolating these findings to disease causality. Physics-informed deep networks, such as TauFlowNet, predict future tau accumulation and propagation from longitudinal tau-PET, while multimodal models combining plasma biomarkers with MRI approximate tau-PET indices for individualized risk stratification. ⁴³ Emerging trends emphasize interpretable, multiscale ML frameworks bridging imaging, molecular, and cellular data to model the “myelin integrity-connectivity-tau spread” axis.^19,38 These integrative approaches highlight OL biology as a promising diagnostic and therapeutic frontier in AD.

This study represents the first bibliometric analysis of OLs in AD, employing quantitative methods to explore the contributions and trends of OLs in the context of AD. However, several limitations must be acknowledged. The literature data used in this study were exclusively sourced from the WOS and Scopus. While this database provides a comprehensive dataset, relying solely on it may introduce selection bias by excluding relevant studies indexed in other major databases such as PubMed. Furthermore, the focus on English-language publications may result in the underrepresentation of research conducted in non-English-speaking regions, thereby limiting the global perspective of our findings. Additionally, our analysis heavily relies on the temporal accumulation of literature data and the consistency of keywords, which inherently introduces certain biases. Given the limitations of the analytical software in handling data heterogeneity, we primarily focused on the most recent period to capture emerging research trends.

Supplemental Material