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TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia
Mackenzie IR, Rademakers R, Neumann M.. The Lancet. Neurology, 2010-10-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Abnormal intracellular protein aggregates comprise a key characteristic in most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The seminal discoveries of accumulation of TDP-43 in most cases of ALS and the most frequent form of FTD, frontotemporal lobar degeneration with ubiquitinated inclusions, followed by identification of FUS as the novel pathological protein in a small subset of patients with ALS and various FTD subtypes provide clear evidence that these disorders are related. The creation of a novel molecular classification of ALS and FTD based on the identity of the predominant protein abnormality has, therefore, been possible. The striking functional and structural similarities of TDP-43 and FUS, which are both DNA/RNA binding proteins, imply that abnormal RNA metabolism is a pivotal event, but the mechanisms leading to TDP-43 and FUS accumulation and the resulting neurodegeneration are currently unknown. Nonetheless, TDP-43 and FUS are promising candidates for the development of novel biomarker assays and targeted therapies.
What this study adds
Evidence grade: Low
This is a narrative review. This review describes how clumps of the proteins TDP-43 and FUS are found in ALS and frontotemporal dementia, leading to a new way of classifying these diseases. It notes that the mechanisms causing these protein clumps and the resulting nerve damage are still unknown, though these proteins are seen as promising candidates for future biomarker tests and targeted therapies.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mackenzie, I. R., Rademakers, R., & Neumann, M. (2010). TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. The Lancet. Neurology. https://doi.org/10.1016/s1474-4422(10)70195-2
Vancouver
Mackenzie IR, Rademakers R, Neumann M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. The Lancet. Neurology. 2010. doi:10.1016/s1474-4422(10)70195-2. PMID: 20864052.
BibTeX
@article{mackenzie2010-20864052,
author = {Mackenzie, I. R. and Rademakers, R. and Neumann, M.},
title = {{TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia}},
journal = {The Lancet. Neurology},
year = {2010},
doi = {10.1016/s1474-4422(10)70195-2},
pmid = {20864052},
url = {https://doi.org/10.1016/s1474-4422(10)70195-2}
}
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.
Key findings
- Abnormal intracellular protein aggregates comprise a key characteristic in most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
- The seminal discoveries of accumulation of TDP-43 in most cases of ALS and the most frequent form of FTD, frontotemporal lobar degeneration with ubiquitinated inclusions, followed by identification of FUS as the novel pathological protein in a small subset of patients with ALS and various FTD subtypes provide clear evidence that these disorders are related.
- The creation of a novel molecular classification of ALS and FTD based on the identity of the predominant protein abnormality has, therefore, been possible.
- The striking functional and structural similarities of TDP-43 and FUS, which are both DNA/RNA binding proteins, imply that abnormal RNA metabolism is a pivotal event, but the mechanisms leading to TDP-43 and FUS accumulation and the resulting neurodegeneration are currently unknown.
- Nonetheless, TDP-43 and FUS are promising candidates for the development of novel biomarker assays and targeted therapies.
Why it matters
This review describes how clumps of the proteins TDP-43 and FUS are found in ALS and frontotemporal dementia, leading to a new way of classifying these diseases. It notes that the mechanisms causing these protein clumps and the resulting nerve damage are still unknown, though these proteins are seen as promising candidates for future biomarker tests and targeted therapies.
Study details
- Evidence strengthLow
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (The Lancet. Neurology) |
| Journal's citation record | 3 / 4 | The Lancet Neurology: journal h-index 457 (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 | 2010 — 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 | 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 957 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 53.2 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 6 / 6 | Cited 44.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 39 other studies in this library |
| Still being cited | 3 / 4 | Cited 138 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Manuela Neumann: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20864052) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
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