Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology.
Open accessAbstract
A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation of the tissue sections with alkaline phosphatase prior to immunolabeling dramatically increased the number of tangles and plaques recognized by the antibody. The plaque core amyloid was not stained in either dephosphorylated or nondephosphorylated tissue sections. On immunoblots PHF polypeptides were labeled readily only when dephosphorylated. In contrast, a commercially available monoclonal antibody to a phosphorylated epitope of neurofilaments that labeled the tangles and the plaque neurites in tissue did not label any PHF polypeptides on immunoblots. The PHF polypeptides, labeled with the monoclonal antibody to tau, electrophoresed with those polypeptides recognized by antibodies to isolated PHF. The antibody to tau-labeled microtubules from normal human brains assembled in vitro but identically treated Alzheimer brain preparations had to be dephosphorylated to be completely recognized by this antibody. These findings suggest that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF.
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Tau hyperphosphorylation triggers the formation of neurofibrillary tangles and is a key pathological hallmark of AD.
“Tau hyperphosphorylation, which triggers the formation of neurofibrillary tangles, is a key pathological hallmark of AD [48].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [48]
The Abstract links abnormally phosphorylated tau to paired-helical filaments in Alzheimer disease neurofibrillary tangles, supporting its association with AD pathology. It does not show that tau hyperphosphorylation triggers tangle formation; the paper describes that conclusion as evidence suggesting tau is a component of the filaments. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAbnormal phosphorylation of tau leads to the formation of paired helical filaments (PHFs), the main components of intraneuronal neurofibrillary tangles.
“In the brain, abnormal phosphorylation of the microtubule-associated protein tau leads to the formation of paired helical filaments (PHFs), the main components of intraneuronal neurofibrillary tangles (Grundke-Iqbal et al., 1986).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Grundke-Iqbal et al., 1986
The Abstract says the findings suggest that abnormally phosphorylated tau is a component of paired helical filaments (PHFs), and identifies neurofibrillary tangles as a major location of PHFs. It does not establish the stronger causal claim that abnormal phosphorylation leads to PHF formation. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAt the cellular level, abnormal tau phosphorylation and the formation of tangles are major events in neuronal degeneration in Alzheimer's disease.
“At the cellular level, abnormal tau phosphorylation and the formation of tangles are major events in neuronal degeneration in Alzheimer’s disease (Grundke-Iqbal et al., 1986).”
From The influence of phospho-tau on dendritic spines of cortical pyramidal neurons in patients with Alzheimer’s disease (2013) · cites this paper as Grundke-Iqbal et al., 1986
The Abstract (p. 4913) identifies neurofibrillary tangles in Alzheimer disease brain and suggests that tau in paired-helical filaments is abnormally phosphorylated. It does not establish that tangle formation and tau phosphorylation are major events in neuronal degeneration. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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- Authors
- Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1986-07
- Volume
- 83
- Issue
- 13
- Pages
- 4913-4917
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC323854
- OpenAlex
- W2036755018
- Cited by
- 3,676
- References
- 3
- Citations by year
- 2026: 88 · 2025: 138 · 2024: 148 · 2023: 135 · 2022: 153 · 2021: 178 · 2020: 179 · 2019: 155 · 2018: 144 · 2017: 144 · 2016: 135 · 2015: 121 · 2014: 153 · 2013: 125 · 2012: 93
- FWCI
- 49.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-05892, P01 AG/NS 04220)
- 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, protein phosphorylation, Alzheimer's disease, neurofibrillary tangles, amyloid plaques, paired helical filaments, microtubule-associated proteins, monoclonal antibodies, dephosphorylation, microtubule assembly, neurofilaments
- MeSH terms
- Alzheimer Disease, Antibodies, Monoclonal, Cytoskeleton, Hippocampus, Humans, Immunologic Techniques, Microtubule-Associated Proteins, Phosphoproteins, Phosphorylation, tau Proteins
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