Sequential Changes of Tau-Site-Specific Phosphorylation during Development of Paired Helical Filaments
Abstract
It has been reported that many tau sites in neurofibrillary tangles (NFT) are abnormally phosphorylated. We investigated the phosphorylation of tau in the hippocampus of nondemented patients and Alzheimer's disease patients by immunostaining with five site-specific antibodies against phosphorylated tau. In the pretangle stage, tau in neuropil threads was phosphorylated at serines 199, 202 and 409, numbered according to the longest human tau isoform, whereas tau in some neuronal soma was phosphorylated at serines 199, 202, 409 and 422. Tau at the stage of NFT was phosphorylated at serine 396 and threonine 231 in addition to serines 199, 202, 409 and 422. In the advanced stage, tau in ghost tangles was phosphorylated mainly at serine 396. These results suggest that the phosphorylation of each site in tau differs among the maturing stages of neurofibrillary change and that abnormal phosphorylation of tau in the neuronal soma occurs at 199, 202, 409 and 422 earlier than at threonine 231 and serine 396.
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Specific tau phosphorylation epitopes are associated with different stages of neurofibrillary tangle formation in Alzheimer disease.
“Several groups have used phosphorylation-dependent tau antibodies and a panel of AD cases of varying severity to map epitopes that were associated with different stages of neurofibrillary tangle formation during disease progression (9, 10).”
From An Unbiased Approach to Identifying Tau Kinases That Phosphorylate Tau at Sites Associated with Alzheimer Disease (2013) · cites this paper as [10]
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- Authors
- Kimura, T., Ono, T., Takamatsu, J., Yamamoto, H., Ikegami, K., Kondo, A., Hasegawa, M., Ihara, Y., Miyamoto, E., & Miyakawa, T.
- Affiliations
- Hizen Psychiatric Center (JP)
- The University of Tokyo (JP)
- Kumamoto University (JP)
- Venue
- Dementia and Geriatric Cognitive Disorders
- Publisher
- S. Karger AG
- Published
- 1996
- Volume
- 7
- Issue
- 4
- Pages
- 177-181
- ISSN
- 1420-8008 (ISSN-L)
- 1421-9824
- OpenAlex
- W1975596414
- Cited by
- 134
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 2 · 2016: 9 · 2015: 4 · 2014: 9 · 2013: 7 · 2012: 6
- FWCI
- 0.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Dementia and Geriatric Cognitive Disorders (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 phosphorylation, site-specific phosphorylation, paired helical filaments, neurofibrillary tangles, Alzheimer's disease, hippocampus, neuropil threads, tau isoforms
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Cytoskeleton, Hippocampus, Humans, Immunohistochemistry, Middle Aged, Phosphorylation, Psychiatric Status Rating Scales, Serine, Threonine, Neurofibrillary Tangles, tau Proteins, Pyramidal Cells
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