Abnormally phosphorylated tau is associated with neuronal and axonal loss in experimental autoimmune encephalomyelitis and multiple sclerosis
Abstract
The pathological correlate of clinical disability and progression in multiple sclerosis is neuronal and axonal loss; however, the underlying mechanisms are unknown. Abnormal phosphorylation of tau is a common feature of some neurodegenerative disorders, such as Alzheimer's disease. We investigated the presence of tau hyperphosphorylation and its relationship with neuronal and axonal loss in chronic experimental autoimmune encephalomyelitis (CEAE) and in brain samples from patients with secondary progressive multiple sclerosis. We report the novel finding of abnormal tau phosphorylation in CEAE. We further show that accumulation of insoluble tau is associated with both neuronal and axonal loss that correlates with progression from relapsing-remitting to chronic stages of EAE. Significantly, analysis of secondary progressive multiple sclerosis brain tissue also revealed abnormally phosphorylated tau and the formation of insoluble tau. Together, these observations provide the first evidence implicating abnormal tau in the neurodegenerative phase of tissue injury in experimental and human demyelinating disease.
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In animal models, demyelination can be triggered by the accumulation of amyloid-beta peptides, phosphorylated Tau, or proinflammatory cytokines.
“In animal models, demyelination can be triggered by the accumulation of amyloid-beta peptides, phosphorylated Tau, or proinflammatory cytokines (35–37).”
From Single-nucleus transcriptome analysis reveals dysregulation of angiogenic endothelial cells and neuroprotective glia in Alzheimer’s disease (2020) · cites this paper as [36]
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- Authors
- Anderson, J. M., Hampton, D. W., Patani, R., Pryce, G., Crowther, R. A., Reynolds, R., Franklin, R. J. M., Giovannoni, G., Compston, D. A. S., Baker, D., Spillantini, M. G., & Chandran, S.
- Affiliations
- University of Cambridge (GB)
- Queen Mary University of London (GB)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-21
- Volume
- 131
- Issue
- 7
- Pages
- 1736-1748
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2136049101
- Cited by
- 141
- References
- 57
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 10 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 8 · 2019: 8 · 2018: 3 · 2017: 12 · 2016: 11 · 2015: 9 · 2014: 4 · 2013: 11 · 2012: 6
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Multiple Sclerosis Society
- Multiple Sclerosis Society (207495)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau hyperphosphorylation, neuronal loss, axonal loss, experimental autoimmune encephalomyelitis, secondary progressive multiple sclerosis, demyelinating disease, neurodegeneration
- MeSH terms
- Animals, Axons, Brain, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Humans, Mice, Inbred Strains, Neurons, Phosphorylation, Blotting, Western, tau Proteins, Cell Death, Multiple Sclerosis, Chronic Progressive, Mice, Biozzi, Mice
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