Phosphorylated serine 199 of microtubule-associated protein tau is a neuronal epitope abundantly expressed in youth and an early marker of tau pathology
Abstract
Microtubule-associated protein tau is abnormally phosphorylated in many neurodegenerative disorders, and is the major component of neurofibrillary degeneration, a degenerating process with many biochemical phenotypes. The serine 199 (S199) residue of tau is phosphorylated at early and late stages of Alzheimer's disease (AD). We studied the immunohistochemical distribution of this phosphorylated epitope in AD and other neurodegenerative disorders, as well as in controls of different ages. The phosphorylated S199 (S199P) epitope was observed in tau lesions from numerous diseases with neurofibrillary degeneration. This epitope was found to be abundantly expressed in the hippocampus formation in childhood and in young adult brain samples, and more specifically in subsets of neurons vulnerable to neurodegeneration. Interestingly, our data suggests that S199P is particularly resistant to phosphatase activity occurring during post-mortem delays. We suggest a peculiar and important role of the S199 residue as a qualitative indicator of the normal and pathological phosphorylation status of tau proteins.
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S199 and T231 are two of the earliest phosphorylated sites on tau in Alzheimer's disease.
“S199 and T231 are two of the earliest phosphorylated sites on tau in AD (Maurage et al., 2003, Luna-Munoz et al., 2007), and tau phosphorylated at S396 is found in paired helical filaments (Bramblett et al., 1993).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Maurage et al., 2003
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Phosphorylation affects the ability of tau protein to promote microtubule assembly.
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Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205
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Tau filament formation in transgenic mice expressing P301L tau
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Hoover, B. R., Reed, M. N., Su, J., Penrod, R. D., Kotilinek, L. A., Grant, M. K., Pitstick, R., Carlson, G. A., Lanier, L. M., Yuan, L.-L., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.030 · Cited by 1,118 · see citing works
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Steinhilb, M. L., Dias-Santagata, D., Fulga, T. A., Felch, D. L., & Feany, M. B. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-04-0327 · Cited by 187 · see citing works
JNK Plays a Key Role in Tau Hyperphosphorylation in Alzheimer's Disease Models
Ploia, C., Antoniou, X., Sclip, A., Grande, V., Cardinetti, D., Colombo, A., Canu, N., Benussi, L., Ghidoni, R., Forloni, G., et al. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110320 · Cited by 145 · see citing works
Sen, T., Saha, P., Jiang, T., & Sen, N. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1916895117 · Cited by 68 · see citing works
Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice
Walker, C. K., Greathouse, K. M., Boros, B. D., Poovey, E. H., Clearman, K. R., Ramdas, R., Muhammad, H. M., & Herskowitz, J. H. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2020.12.006 · Cited by 27 · see citing works
- Authors
- Maurage, C.-A., Sergeant, N., Ruchoux, M.-M., Hauw, J.-J., & Delacourte, A.
- Affiliations
- Centre Hospitalier Universitaire de Lille (FR)
- Inserm (FR)
- Corresponding author
- Delacourte, André
- Venue
- Acta Neuropathologica
- Published
- 2003-02
- Volume
- 105
- Issue
- 2
- Pages
- 89-97
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2151307579
- Cited by
- 51
- References
- 4
- Citations by year
- 2026: 6 · 2025: 1 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 2 · 2018: 1 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, tau phosphorylation, Alzheimer's disease, neurofibrillary degeneration, hippocampus, age-related expression, neurodegeneration, neurodegenerative diseases
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Epitopes, Brain, Child, Humans, Immunohistochemistry, Middle Aged, Nerve Degeneration, Neurons, Phosphorylation, Serine, Biomarkers, Neurofibrillary Tangles, tau Proteins, Neurodegenerative Diseases
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