Home › Research › Risk factors
Mutations causing neurodegenerative tauopathies
Goedert M, Jakes R.. Biochimica et biophysica acta, 2005-01-01
Topic: Brain proteins, microglia and lab models
Tau is the major component of the intracellular filamentous deposits that define a number of neurodegenerative diseases. They include the largely sporadic Alzheimer's disease (AD), progressive supranuclear palsy, corticobasal degeneration, Pick's disease and argyrophilic grain disease, as well as the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). For a long time, it was unclear whether the dysfunction of tau protein follows disease or whether disease follows tau dysfunction. This was resolved when mutations in Tau were found to cause FTDP-17. Currently, 32 different mutations have been identified in over 100 families. About half of the known mutations have their primary effect at the protein level. They reduce the ability of tau protein to interact with microtubules and increase its propensity to assemble into abnormal filaments. The other mutations have their primary effect at the RNA level and perturb the normal ratio of three-repeat to four-repeat tau isoforms. Where studied, this resulted in a relative overproduction of tau protein with four microtubule-binding domains in the brain. Individual Tau mutations give rise to diseases that resemble progressive supranuclear palsy, corticobasal degeneration or Pick's disease. Moreover, the H1 haplotype of Tau has been identified as a significant risk factor for progressive supranuclear palsy and corticobasal degeneration. At a practical level, the new work is leading to the production of experimental animal models that reproduce the essential molecular and cellular features of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and nerve cell degeneration.
Key findings
- Moreover, the H1 haplotype of Tau has been identified as a significant risk factor for progressive supranuclear palsy and corticobasal degeneration.
Why it matters
This review describes how mutations in the tau gene cause inherited frontotemporal dementia and parkinsonism linked to chromosome 17, and how these mutations affect tau protein or its RNA. It explains disease mechanisms in rare inherited tau disorders and does not report a treatment, cure or prevention for Alzheimer's disease.
New to this subject? Start with our plain-English guide: Risk factors, ranked →
Study details
- Evidence strengthLow
How this study scored 46/100
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 journal's citation record, so that was left out: it earned 44 of the 96 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Biochimica et biophysica acta) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2005 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 438 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.0 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 4 / 6 | Cited 12.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 14 other studies in this library |
| Still being cited | 3 / 4 | Cited 57 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Ross Jakes: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | MRC Laboratory of Molecular Biology: institution h-index 816 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15615642) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 44 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 44 of the 96 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.bbadis.2004.08.007
- PubMed: 15615642
- Original source →
- Free full text: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease →
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
Goedert, M., & Jakes, R. (2005). Mutations causing neurodegenerative tauopathies. Biochimica et biophysica acta. https://doi.org/10.1016/j.bbadis.2004.08.007
Vancouver
Goedert M, Jakes R. Mutations causing neurodegenerative tauopathies. Biochimica et biophysica acta. 2005. doi:10.1016/j.bbadis.2004.08.007. PMID: 15615642.
BibTeX
@article{goedert2005-15615642,
author = {Goedert, M. and Jakes, R.},
title = {{Mutations causing neurodegenerative tauopathies}},
journal = {Biochimica et biophysica acta},
year = {2005},
doi = {10.1016/j.bbadis.2004.08.007},
pmid = {15615642},
url = {https://doi.org/10.1016/j.bbadis.2004.08.007}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 16.
Later studies that cite this one
14 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Risk factors
Also tagged “phosphorylated”
732 studies in the library carry the topic tag “phosphorylated”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 732 tagged studies.