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Review
. 2025 Apr;22(3):e00540.
doi: 10.1016/j.neurot.2025.e00540. Epub 2025 Feb 11.

Astrocyte and oligodendrocyte pathology in Alzheimer's disease

Rania Ziar  1 , Paul J Tesar  2 , Benjamin L L Clayton  3
Affiliations
Review

Astrocyte and oligodendrocyte pathology in Alzheimer's disease

Rania Ziar et al. Neurotherapeutics. 2025 Apr.

Abstract

Astrocytes and oligodendrocytes, once considered passive support cells, are now recognized as active participants in the pathogenesis of Alzheimer's disease. Emerging evidence highlights the critical role that these glial cells play in the pathological features of Alzheimer's, including neuroinflammation, excitotoxicity, synaptic dysfunction, and myelin degeneration, which contribute to neurodegeneration and cognitive decline. Here, we review the current understanding of astrocyte and oligodendrocyte pathology in Alzheimer's disease and highlight research that supports the therapeutic potential of modulating astrocyte and oligodendrocyte functions to treat Alzheimer's disease.

Keywords: Alzheimer's; Astrocyte; Glia; Oligodendrocyte.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Paul J Tesar reports a relationship with Convelo Therapeutics that includes: board membership, consulting or advisory, and equity or stocks. Paul J Tesar has issued patents and patents pending to Convelo Therapeutics related to remyelinating therapeutics. Paul J Tesar and Benjamin LL Clayton have patents pending has patents pending related to treating neurodegenerative diseases. Rania Ziar declares that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Astrocyte pathology in Alzheimer's disease. Figure highlights key examples of astrocyte pathological features in Alzheimer's disease. These pathological features include loss of the homeostatic function to uptake neurotransmitters, like glutamate, and gain of the pathological functions to secrete proinflammatory cytokines and contribute to increased Aβ deposition. Approaches designed to restore the homeostatic functions of astrocytes, or suppress the pathological functions of astrocytes, could provide therapeutic benefit in AD. Created in BioRender. Clayton, B. (2024) BioRender.com/l06q743.
Fig. 2
Fig. 2
Oligodendrocyte and myelin pathology in Alzheimer's disease. Figure highlights key pathological features of oligodendrocytes and myelin in Alzheimer's disease. These pathological features include decreased oligodendrocyte differentiation, contribution to plaques by Aβ derived from oligodendrocytes, myelin damage, and degeneration of demyelinated axons. Therapeutics designed to slow or reverse the pathological features of oligodendrocytes and myelin may halt, slow, or reverse the progression of AD. Created in BioRender. Clayton, B. (2024) BioRender.com/j73b486.
Fig. 3
Fig. 3
Potential astrocyte and oligodendrocyte targeted therapies for Alzheimer's disease. The figure highlights experimental manipulations of astrocyte and oligodendrocyte pathology that attenuate pathology in models of Alzheimer's disease. These findings support the development of astrocyte, and oligodendrocyte-targeted therapeutics to halt, slow, or reverse the progression of AD. Created in BioRender. Clayton, B. (2025) BioRender.com/r03l163.
See this image and copyright information in PMC

References

    1. 2024 Alzheimer's disease facts and figures. Alzheimers Dement. 2024;20(5):3708–3821. - PMC - PubMed
    1. Thinakaran G., Koo E.H. Amyloid precursor protein trafficking, processing, and function. J Biol Chem. 2008;283(44):29615–29619. - PMC - PubMed
    1. Grundke-Iqbal I., Iqbal K., Tung Y.C., Quinlan M., Wisniewski H.M., Binder L.I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A. 1986;83(13):4913–4917. - PMC - PubMed
    1. Brandebura A.N., Paumier A., Onur T.S., Allen N.J. Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders. Nat Rev Neurosci. 2023;24(1):23–39. - PMC - PubMed
    1. Nave K.A. Myelination and the trophic support of long axons. Nat Rev Neurosci. 2010;11(4):275–283. - PubMed