Immunohistochemical study of tau accumulation in early stages of Alzheimer-type neurofibrillary lesions
Abstract
Accumulation of abnormally phosphorylated tau results in the formation of neurofibrillary tangles (NFTs) in the neuronal cell soma and neuropil threads (NTs) in the cell processes. In the present study, we used immunohistochemistry to investigate serially cut thick tissue sections from the brains of patients with Alzheimer's disease (AD) and non-demented elderly subjects. In the early stages of neurofibrillary pathology, clusters of NTs occurred occasionally in the cerebral cortex. Each NTs cluster, the entire extent of which was observed in the serial sections, corresponded to a dendritic tree that was arborized from a tau-positive neuron. Adult human brain contains six tau isoforms with three having three carboxyl-terminal tandem repeat sequences that are encoded by exon 10 (3R-tau) and the other three having four repeat sequences (4R-tau). Three isoform patterns, 3R-tau(+)/4R-tau(-), 3R-tau(-)/4R-tau(+) and 3R-tau(+)/4R-tau(+), were seen in NFTs in early stage AD lesions. In an individual neuron, the isoform pattern was consistent between the NFTs in the cell soma and the NTs in the cell processes. The results of this study indicate that, in early stages of AD and age-associated neurofibrillary changes, tau accumulates simultaneously in the cell soma and cell processes of affected neurons. The process of AD and age-associated tau pathology is not tau-isoform-specific, but the ratio of 3R-tau and 4R-tau isoforms involved in the neurofibrillary changes varies and is specific…
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TSC is caused by a pathogenic variant in either TSC1 or TSC2.
“TSC is caused by a pathogenic variant in either TSC1 (coding for hamartin) located on chromosome 9q34 [23] or TSC2 (coding for tuberin) located on chromosome 16p13 [7].”
From Tuberous sclerosis complex is associated with a novel human tauopathy (2023) · cites this paper as [23]
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- Authors
- Togo, T., Akiyama, H., Iseki, E., Uchikado, H., Kondo, H., Ikeda, K., Tsuchiya, K., de Silva, R., Lees, A., & Kosaka, K.
- Affiliations
- Tokyo Institute of Psychiatry (JP)
- Yokohama City University (JP)
- Tokyo Metropolitan Matsuzawa Hospital (JP)
- The Royal Free Hospital (GB)
- Corresponding author
- Akiyama, Haruhiko
- Venue
- Acta Neuropathologica
- Published
- 2004-03-16
- Volume
- 107
- Issue
- 6
- Pages
- 504-508
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2064800313
- Cited by
- 38
- References
- 22
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2014: 2 · 2013: 4
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Fonden til Lægevidenskabens Fremme
- 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, neuropil threads, Alzheimer's disease, tau isoforms, 3R tau, 4R tau, cerebral cortex, phosphorylated tau
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, Neurofibrillary Tangles, tau Proteins
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