Oligodendrocytes in Alzheimer’s disease pathophysiology
Abstract
Our understanding of Alzheimer's disease (AD) has transformed from a purely neuronal perspective to one that acknowledges the involvement of glial cells. Despite remarkable progress in unraveling the biology of microglia, astrocytes and vascular elements, the exploration of oligodendrocytes in AD is still in its early stages. Contrary to the traditional notion of oligodendrocytes as passive bystanders in AD pathology, emerging evidence indicates their active participation in and reaction to amyloid and tau pathology. Oligodendrocytes undergo a functional transition to a disease-associated state, engaging in immune modulation, stress responses and cellular survival. Far from being inert players, they appear to serve a dual role in AD pathogenesis, potentially offering defense mechanisms against pathology while also contributing to disease progression. This Review explores recent advancements in understanding the roles of oligodendrocytes and their myelin sheaths in the context of AD, shedding light on their complex interactions within the disease pathology.
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Oligodendrocytes actively respond to AD pathology, transitioning into reactive, "disease-associated" states marked by immune and stress-response genes.
“This aligns with emerging evidence that oligodendrocytes actively respond to AD pathology, transitioning into reactive, “disease‐associated” states marked by immune and stress‐response genes. 61”
From Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial–oligodendrocyte responses (2026) · cites this paper as [61]
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Chimeric brain models to study human glial-neuronal and macroglial-microglial interactions
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- Authors
- Kedia, S., & Simons, M.
- Affiliations
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Simons, Mikael
- Venue
- Nature Neuroscience
- Published
- 2025-01-29
- Volume
- 28
- Issue
- 3
- Pages
- 446-456
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W4406931967
- Cited by
- 86
- References
- 42
- Citations by year
- 2026: 53 · 2025: 33
- FWCI
- 11.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- oligodendrocytes, Alzheimer's disease, myelin sheath, amyloid pathology, tau pathology, glial cells, immunomodulation, stress response, cell survival, disease progression
- MeSH terms
- Alzheimer Disease, Animals, Humans, Myelin Sheath, Oligodendroglia
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