Along the way to a neurofibrillary tangle: a look at the structure of tau
Abstract
We report our ongoing work to characterize the molecular nature of neurofibrillary tangles (NFT). An epitope map of tau protein using monoclonal antibodies that crossreact with NFT reveals the presence of epitopes that span the entire tau molecule from the amino terminus to the carboxy terminus. Several antibodies that recognize tau protein including Alz50 do not recognize primary amino acid sequence but are directed either against a post-translational modification or a complex higher order structure. The importance of tau protein in the development of the pathology is underscored by the extent of the tau-reactive neuritic lesions. These dystrophic neurites or "curly fibers" extend well beyond the classical distributions of the senile plaques and NFT. Furthermore, the neuropil lesion is considerably more extensive than either the senile plaques or neurofibrillary tangles. One of the features of the dystrophy in Alzheimer's disease is widespread neuronal sprouting characteristic of dystrophic neurites and tangle-bearing cells.
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Tauopathies are neurodegenerative diseases characterized by pathological accumulation of hyper-phosphorylated tau in paired helical filaments or neurofibrillary tangles within neurons and glia of affected brain regions, leading to cell death.
“Tauopathies are neurodegenerative diseases characterized by aberrant forms of tau protein accumulation leading to neuronal death in focal brain areas.”
From Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models (2019) · cites this paper as Kosik et al., 1989
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Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models
Silva, M. C., Ferguson, F. M., Cai, Q., Donovan, K. A., Nandi, G., Patnaik, D., Zhang, T., Huang, H.-T., Lucente, D. E., Dickerson, B. C., et al. (2019) · eLife · doi:10.7554/elife.45457 · Cited by 283 · see citing works
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- Authors
- Kosik, K. S., Kowall, N. W., & McKee, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Annals of Medicine
- Publisher
- Informa UK Limited
- Published
- 1989-01
- Volume
- 21
- Issue
- 2
- Pages
- 109-112
- ISSN
- 0785-3890 (ISSN-L)
- 1365-2060
- OpenAlex
- W1988360179
- Cited by
- 31
- References
- 32
- Citations by year
- 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 1
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Medicine (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, neurofibrillary tangles, epitope mapping, monoclonal antibodies, post-translational modification, protein higher-order structure, dystrophic neurites, amyloid plaques, nerve sprouting, Alzheimer's disease pathology
- MeSH terms
- Alzheimer Disease, Amyloidosis, Antibodies, Monoclonal, Cross Reactions, Dendrites, Humans, Microtubule-Associated Proteins, Nerve Tissue Proteins, Neurofibrils, Protein Processing, Post-Translational, tau Proteins
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