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Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43
Davidson Y, Kelley T, Mackenzie IR, Pickering-Brown S, Du Plessis D, Neary D, Snowden JS, Mann DM.. Acta neuropathologica, 2007-01-12
Topic: Brain proteins, microglia and lab models
We have investigated the extent and pattern of immunostaining for the TAR DNA-binding protein, TDP-43, in 37 patients with frontotemporal lobar degeneration with ubiquitin (UBQ) pathology (FTLD-U). We confirm that TDP-43 protein is a component of the UBQ immunoreactive (UBQ-ir) neuronal cytoplasmic inclusions (NCI), neuronal intranuclear inclusions (NII) and neurites of the cerebral cortex and hippocampus in FTLD-U. We further show that the same three histological patterns, previously identified by us according to the form, number and distribution of the UBQ-ir NCI, NII and neurites are equivalently present in TDP-43 immunohistochemistry.
Key findings
- We confirm that TDP-43 protein is a component of the UBQ immunoreactive (UBQ-ir) neuronal cytoplasmic inclusions (NCI), neuronal intranuclear inclusions (NII) and neurites of the cerebral cortex and hippocampus in FTLD-U.
- We further show that the same three histological patterns, previously identified by us according to the form, number and distribution of the UBQ-ir NCI, NII and neurites are equivalently present in TDP-43 immunohistochemistry.
- TDP-43 immunoreactive (TDP-43-ir) NCI with rounded, spicular or skein-type appearance were seen in motor neurones of the trigeminal or facial cranial nerve nuclei in one patient with frontotemporal dementia (FTD) and in the spinal cord in three patients with FTD + motor neurone disease (MND).
- In patients with MND alone, TDP-43-ir NCI are common in anterior horn cells of the spinal cord, and occasionally seen in neurones of the hypoglossus nucleus.
Why it matters
In brain tissue from 37 people with frontotemporal lobar degeneration with ubiquitin pathology (FTLD-U), this study confirmed that the protein TDP-43 is part of the abnormal inclusions in the cortex and hippocampus, and that the three inclusion patterns the authors had earlier described with ubiquitin staining look the same with TDP-43 staining. Similar TDP-43 inclusions were seen in motor neurones of a few patients with FTD or FTD plus motor neurone disease, and were common in spinal cord motor neurones in motor neurone disease alone. The study describes tissue findings in FTLD and MND, not Alzheimer's disease, and reports no test, treatment or prevention.
Study details
- Participants37
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (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 | 2007 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 37 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 301 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.3 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 5 / 6 | Cited 28.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 30 other studies in this library |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author David Mann: h-index 99 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Manchester: institution h-index 1,304 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17219193) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Davidson, Y., Kelley, T., Mackenzie, I. R., Pickering-Brown, S., Du Plessis, D., Neary, D., et al. (2007). Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta neuropathologica. https://doi.org/10.1007/s00401-006-0189-y
Vancouver
Davidson Y, Kelley T, Mackenzie IR, Pickering-Brown S, Du Plessis D, Neary D, et al. Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta neuropathologica. 2007. doi:10.1007/s00401-006-0189-y. PMID: 17219193.
BibTeX
@article{davidson2007-17219193,
author = {Davidson, Y. and Kelley, T. and Mackenzie, I. R. and Pickering-Brown, S. and Du Plessis, D. and Neary, D. and Snowden, J. S. and Mann, D. M.},
title = {{Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43}},
journal = {Acta neuropathologica},
year = {2007},
doi = {10.1007/s00401-006-0189-y},
pmid = {17219193},
url = {https://doi.org/10.1007/s00401-006-0189-y}
}
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