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Mutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B.. Proceedings of the National Academy of Sciences of the United States of America, 1998-06-01
Topic: Brain proteins, microglia and lab models
Familial multiple system tauopathy with presenile dementia (MSTD) is a neurodegenerative disease with an abundant filamentous tau protein pathology. It belongs to the group of familial frontotemporal dementias with Parkinsonism linked to chromosome 17 (FTDP-17), a major class of inherited dementing disorders whose genetic basis is unknown. We now report a G to A transition in the intron following exon 10 of the gene for microtubule-associated protein tau in familial MSTD. The mutation is located at the 3' neighboring nucleotide of the GT splice-donor site and disrupts a predicted stem-loop structure. We also report an abnormal preponderance of soluble tau protein isoforms with four microtubule-binding repeats over isoforms with three repeats in familial MSTD. This most likely accounts for our previous finding that sarkosyl-insoluble tau protein extracted from the filamentous deposits in familial MSTD consists only of tau isoforms with four repeats. These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments. The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer's disease and other tauopathies.
Key findings
- These findings reveal that a departure from the normal ratio of four-repeat to three-repeat tau isoforms leads to the formation of abnormal tau filaments.
- The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene.
Why it matters
A mutation in the tau gene was found in familial multiple system tauopathy with presenile dementia, along with an abnormal preponderance of four-repeat over three-repeat tau isoforms that formed abnormal tau filaments. This shows that dysregulated tau production can cause neurodegeneration, but it is a genetic finding with no treatment tested.
Study details
- Evidence strengthLow
How this study scored 57/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (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 | 1998 — 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 | 7 / 7 | Cited 1,477 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 49.2 citations a year over 30 year(s) since 1998 |
| Impact for its field and year | 6 / 6 | Cited 50.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 59 other studies in this library |
| Still being cited | 3 / 4 | Cited 74 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bernardino Francesco Ghetti: h-index 121 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 9636220) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Spillantini, M. G., Murrell, JR., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998). Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.95.13.7737
Vancouver
Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proceedings of the National Academy of Sciences of the United States of America. 1998. doi:10.1073/pnas.95.13.7737. PMID: 9636220.
BibTeX
@article{spillantini1998-9636220,
author = {Spillantini, M. G. and Murrell, JR. and Goedert, M. and Farlow, M. R. and Klug, A. and Ghetti, B.},
title = {{Mutation in the tau gene in familial multiple system tauopathy with presenile dementia}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {1998},
doi = {10.1073/pnas.95.13.7737},
pmid = {9636220},
url = {https://doi.org/10.1073/pnas.95.13.7737}
}
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