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Hyperphosphorylation-induced tau oligomers
Iqbal K, Gong CX, Liu F.. Frontiers in neurology, 2013-08-15
Topic: Brain proteins, microglia and lab models
In normal adult brain the microtubule associated protein (MAP) tau contains 2-3 phosphates per mol of the protein and at this level of phosphorylation it is a soluble cytosolic protein. The normal brain tau interacts with tubulin and promotes its assembly into microtubules and stabilizes these fibrils. In Alzheimer disease (AD) brain tau is three to fourfold hyperphosphorylated. The abnormally hyperphosphorylated tau binds to normal tau instead of the tubulin and this binding leads to the formation of tau oligomers. The tau oligomers can be sedimented at 200,000 × g whereas the normal tau under these conditions remains in the supernatant. The abnormally hyperphosphorylated tau is capable of sequestering not only normal tau but also MAP MAP1 and MAP2 and causing disruption of the microtubule network promoted by these proteins. Unlike Aβ and prion protein (PrP) oligomers, tau oligomerization in AD and related tauopathies is hyperphosphorylation-dependent; in vitro dephosphorylation of AD P-tau with protein phosphatase 2A (PP2A) inhibits and rehyperphosphorylation of the PP2A-AD P-tau with more than one combination of tau protein kinases promotes its oligomerization. In physiological assembly conditions the AD P-tau readily self-assembles into paired helical filaments. Missense tau mutations found in frontotemporal dementia apparently lead to tau oligomerization and neurofibrillary pathology by promoting its abnormal hyperphosphorylation. Dysregulation of the alternative splicing of tau that alters the 1:1 ratio of the 3-repeat: 4-repeat taus such as in Down syndrome, Pick disease, and progressive supranuclear palsy leads to the abnormal hyperphosphorylation of tau.
Key findings
- The abnormally hyperphosphorylated tau is capable of sequestering not only normal tau but also MAP MAP1 and MAP2 and causing disruption of the microtubule network promoted by these proteins.
- Unlike Aβ and prion protein (PrP) oligomers, tau oligomerization in AD and related tauopathies is hyperphosphorylation-dependent; in vitro dephosphorylation of AD P-tau with protein phosphatase 2A (PP2A) inhibits and rehyperphosphorylation of the PP2A-AD P-tau with more than one combination of tau protein kinases promotes its oligomerization.
- In physiological assembly conditions the AD P-tau readily self-assembles into paired helical filaments.
- Missense tau mutations found in frontotemporal dementia apparently lead to tau oligomerization and neurofibrillary pathology by promoting its abnormal hyperphosphorylation.
- Dysregulation of the alternative splicing of tau that alters the 1:1 ratio of the 3-repeat: 4-repeat taus such as in Down syndrome, Pick disease, and progressive supranuclear palsy leads to the abnormal hyperphosphorylation of tau.
Why it matters
This paper describes how abnormally hyperphosphorylated tau binds normal tau and forms tau oligomers, and that dephosphorylation with protein phosphatase 2A inhibits this while rehyperphosphorylation promotes it. It is a mechanistic account of tau behavior and reports no treatment, cure, or prevention.
Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on institution's track record, so that was left out: it earned 41 of the 97 points we could judge it on, which is 42 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in neurology) |
| Journal's citation record | 2 / 4 | Frontiers in Neurology: journal h-index 162 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 112 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.5 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 3 / 6 | Cited 6.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Fei Liu: h-index 59 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23966973) |
| Free to read | 2 / 2 | Free to read |
| Points | 41 / 97 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 41 of the 97 points we could judge it on is 42 out of 100. |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fneur.2013.00112
- PubMed: 23966973
- Original source →
- Free full text: Frontiers in Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Iqbal, K., Gong, C. X., & Liu, F. (2013). Hyperphosphorylation-induced tau oligomers. Frontiers in neurology. https://doi.org/10.3389/fneur.2013.00112
Vancouver
Iqbal K, Gong CX, Liu F. Hyperphosphorylation-induced tau oligomers. Frontiers in neurology. 2013. doi:10.3389/fneur.2013.00112. PMID: 23966973.
BibTeX
@article{iqbal2013-23966973,
author = {Iqbal, K. and Gong, C. X. and Liu, F.},
title = {{Hyperphosphorylation-induced tau oligomers}},
journal = {Frontiers in neurology},
year = {2013},
doi = {10.3389/fneur.2013.00112},
pmid = {23966973},
url = {https://doi.org/10.3389/fneur.2013.00112}
}
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