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Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Nakashima-Yasuda H, Uryu K, Robinson J, Xie SX, Hurtig H, Duda JE, Arnold SE, Siderowf A et al.. Acta neuropathologica, 2007-07-25
Topic: Brain proteins, microglia and lab models
Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson's disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer's disease (AD). Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD = 4/21 (19%), while DLB and normal controls exhibited no (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively. Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001). Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases. This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders.
Key findings
- Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD = 4/21 (19%), while DLB and normal controls exhibited no (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively.
- Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001).
- Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases.
Why it matters
Examining 213 brains after death, the researchers looked for clumps of TDP-43, a protein best known from some frontotemporal dementias and ALS, and found them in 25 of 80 brains with both dementia with Lewy bodies and Alzheimer's, 4 of 21 with Parkinson's dementia and 5 of 69 with Parkinson's without dementia, but in none of 10 with Lewy body dementia alone and 1 of 33 healthy brains. The clumps were significantly more common in diseased than normal brains and in brains of people who had dementia, which the authors say suggests TDP-43 "may have co-morbid effects" in Lewy body diseases. This shows the proteins occurring together, not that TDP-43 causes the dementia, and the highest rate was in brains that also had Alzheimer's.
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Study details
- Effect size31.3%; 7.2%
- Evidence strengthLow
How this study scored 59/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 467 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.2 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 5 / 6 | Cited 23.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 45 other studies in this library |
| Still being cited | 3 / 4 | Cited 67 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John Q. Trojanowski: h-index 255 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 17653732) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
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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
Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., et al. (2007). Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta neuropathologica. https://doi.org/10.1007/s00401-007-0261-2
Vancouver
Nakashima-Yasuda H, Uryu K, Robinson J, Xie SX, Hurtig H, Duda JE, et al. Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta neuropathologica. 2007. doi:10.1007/s00401-007-0261-2. PMID: 17653732.
BibTeX
@article{nakashimayasuda2007-17653732,
author = {Nakashima-Yasuda, H. and Uryu, K. and Robinson, J. and Xie, S. X. and Hurtig, H. and Duda, J. E. and Arnold, S. E. and Siderowf, A. and others},
title = {{Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases}},
journal = {Acta neuropathologica},
year = {2007},
doi = {10.1007/s00401-007-0261-2},
pmid = {17653732},
url = {https://doi.org/10.1007/s00401-007-0261-2}
}
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