Glial and Neuronal Tau Pathology in Tauopathies: Characterization of Disease-Specific Phenotypes and Tau Pathology Progression
Abstract
Tauopathies are degenerative diseases characterized by the accumulation of phosphorylated tau in neurons and glial cells. With some exceptions, tau deposits in neurons are mainly manifested as pretangles and tangles unrelated to the tauopathy. It is thought that abnormal tau deposition in neurons occurs following specific steps, but little is known about the progression of tau pathology in glial cells in tauopathies. We compared tau pathology in different astrocyte phenotypes and oligodendroglial inclusions with that in neurons in a large series of tauopathies, including progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick disease, frontotemporal lobar degenerations (FTLD) associated with mutations in the tau gene, globular glial tauopathy (GGT), and tauopathy in the elderly. Our findings indicate that disease-specific astroglial phenotypes depend on i) the primary amino acid sequence of tau (mutated tau, 3Rtau, and 4Rtau); ii) phospho-specific sites of tau phosphorylation, tau conformation, tau truncation, and ubiquitination in that order (which parallel tau modifications related to pretangle and tangle stages in neurons); and iii) modifications of the astroglial cytoskeleton. In contrast to astrocytes, coiled bodies in oligodendrocytes have similar characteristics whatever the tauopathy, except glial globular inclusions in GGT, and coiled bodies and globular oligodendroglial inclusions in FTLD-tau/K317M. These observations indicate that tau pathology in glial cells largely parallels, but is not identical to, that in neurons in many tauopathies.
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Most tauopathies have neuronal and glial accumulations of toxic insoluble tau, neuronal loss, and proinflammatory microglia.
“Most tauopathies have neuronal and glial accumulations of toxic insoluble tau, neuronal loss, and proinflammatory microglia47.”
From Microglia in neurodegeneration (2018) · cites this paper as [47]
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- Authors
- Ferrer, I., López-González, I., Carmona, M., Arregui, L., Dalfó, E., Torrejón-Escribano, B., Diehl, R., & Kovacs, G. G.
- Affiliations
- Bellvitge University Hospital (ES)
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-01
- Volume
- 73
- Issue
- 1
- Pages
- 81-97
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2319874712
- Cited by
- 217
- References
- 50
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 15 · 2023: 16 · 2022: 27 · 2021: 22 · 2020: 19 · 2019: 21 · 2018: 23 · 2017: 16 · 2016: 9 · 2015: 13 · 2014: 8
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tauopathy, tau phosphorylation, astrocytes, oligodendrocytes, globular glial tauopathy, progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, Pick's disease, frontotemporal lobar degeneration, tau mutations, tau truncation, coiled bodies, globular inclusions
- MeSH terms
- Brain, Humans, Neuroglia, Neurons, Phenotype, tau Proteins, Disease Progression, Tauopathies
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