Accumulation of abnormally phosphorylated τ precedes the formation of neurofibrillary tangles in Alzheimer's disease
Abstract
The intraneuronal accumulation of paired helical filaments in the form of neurofibrillary tangles is one hallmark of the brain pathology in Alzheimer's disease. At certain predilection sites, a small number of similar lesions are also present in the brains of the majority of aged non-demented individuals. As suggested by several studies before, these abnormal cytoskeletal structures contain determinants of microtubule-associated protein tau and ubiquitin. The present study uses a morphological classification of neurofibrillary tangles into different stages of maturation, as suggested by Alzheimer in 1911, and shows by quantitative immunocytochemistry that early stages of neurofibrillary degeneration contain abnormally phosphorylated tau. Immunoreactivity for the altered tau is seen not only in tangles but also in the cytoplasm of some nerve cells lacking neurofibrillary tangles. Similar numbers of such immunoreactive neurons without tangles are present in age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls. In contrast, incorporation of an epitope, recognized by a monoclonal antibody (3-39) raised to paired helical filaments, which is directed against a determinant residing in the 50-65 amino acid residue region of ubiquitin occurs late in the process of tangle maturation and is most pronounced in extracellular 'ghost tangles'. It is suggested that the accumulation of abnormally phosphorylated tau is one of the earliest cytoskeletal ch…
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Tau is hyperphosphorylated in the brains of patients with Alzheimer's disease.
“An important post-translational modification is phosphorylation, because Tau is hyperphosphorylated in the brains of patients with Alzheimer’s disease74.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [74]
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- Authors
- Bancher, C., Brunner, C., Lassmann, H., Budka, H., Jellinger, K., Wiche, G., Seitelberger, F., Grundke-Iqbal, I., Iqbal, K., & Wisniewski, H. M.
- Affiliations
- University of Vienna (AT)
- Corresponding author
- Bancher, C.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1989-01
- Volume
- 477
- Issue
- 1-2
- Pages
- 90-99
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2077422298
- Cited by
- 818
- References
- 1
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 16 · 2023: 20 · 2022: 20 · 2021: 25 · 2020: 36 · 2019: 20 · 2018: 16 · 2017: 17 · 2016: 24 · 2015: 19 · 2014: 17 · 2013: 30 · 2012: 22
- FWCI
- 21.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG04220, AG-05892)
- National Institute of Neurological Disorders and Stroke (NS 18105)
- 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, Alzheimer's disease, paired helical filaments, ubiquitin, cytoskeletal changes, proteolysis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Glial Fibrillary Acidic Protein, Humans, Microscopy, Electron, Microtubule-Associated Proteins, Middle Aged, Nerve Tissue Proteins, Neurofibrils, Phosphorylation, Reference Values, tau Proteins
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