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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T et al.. Science (New York, N.Y.), 2006-10-01
Topic: Brain proteins, microglia and lab models
Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.
Key findings
- Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders.
Why it matters
Before this study, the ubiquitinated protein inside the tau- and alpha-synuclein-negative inclusions of frontotemporal lobar degeneration (FTLD-U) and ALS was unknown. The authors report that it is TDP-43, which they found in an abnormal form ("hyper-phosphorylated, ubiquitinated, and cleaved") only in affected brain and spinal cord regions. They conclude it is "the common pathologic substrate linking these neurodegenerative disorders". The study is about FTLD and ALS, not Alzheimer's disease, and it does not test any treatment, test or prevention.
Study details
- Evidence strengthLow
How this study scored 62/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (Science (New York, N.Y.)) |
| Journal's citation record | 4 / 4 | Science: journal h-index 1,754 (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 | 2006 — 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 6,587 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 299.4 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 6 / 6 | Cited 104.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 6 / 6 | Cited by 272 other studies in this library |
| Still being cited | 4 / 4 | Cited 1,133 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Virginia M.‐Y. Lee: h-index 202 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Pennsylvania: institution h-index 1,859 (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 17023659) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., et al. (2006). Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science (New York, N.Y.). https://doi.org/10.1126/science.1134108
Vancouver
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science (New York, N.Y.). 2006. doi:10.1126/science.1134108. PMID: 17023659.
BibTeX
@article{neumann2006-17023659,
author = {Neumann, M. and Sampathu, D. M. and Kwong, L. K. and Truax, A. C. and Micsenyi, M. C. and Chou, T. T. and Bruce, J. and Schuck, T. and others},
title = {{Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis}},
journal = {Science (New York, N.Y.)},
year = {2006},
doi = {10.1126/science.1134108},
pmid = {17023659},
url = {https://doi.org/10.1126/science.1134108}
}
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