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Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations
Mackenzie IR, Arzberger T, Kremmer E, Troost D, Lorenzl S, Mori K, Weng SM, Haass C et al.. Acta neuropathologica, 2013-10-06
Topic: Brain proteins, microglia and lab models
Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of frontotemporal dementia and motor neuron disease. Recently, unconventional non-ATG translation of the expanded hexanucleotide repeat, resulting in the production and aggregation of dipeptide repeat (DPR) proteins (poly-GA, -GR and GP), was identified as a potential pathomechanism of C9ORF72 mutations. Besides accumulation of DPR proteins, the second neuropathological hallmark lesion in C9ORF72 mutation cases is the accumulation of TDP-43.
Key findings
- Recently, unconventional non-ATG translation of the expanded hexanucleotide repeat, resulting in the production and aggregation of dipeptide repeat (DPR) proteins (poly-GA, -GR and GP), was identified as a potential pathomechanism of C9ORF72 mutations.
- Besides accumulation of DPR proteins, the second neuropathological hallmark lesion in C9ORF72 mutation cases is the accumulation of TDP-43.
- In this study, we characterized novel monoclonal antibodies against poly-GA and performed a detailed analysis of the neuroanatomical distribution of DPR and TDP-43 pathology in a cohort of 35 cases with the C9ORF72 mutation that included a broad spectrum of clinical phenotypes.
- We found the pattern of DPR pathology to be highly consistent among cases regardless of the phenotype with high DPR load in the cerebellum, all neocortical regions (frontal, motor cortex and occipital) and hippocampus, moderate pathology in subcortical areas and minimal pathology in lower motor neurons.
Why it matters
This study characterized new antibodies against dipeptide repeat proteins and analyzed their pathology in cases with C9ORF72 mutations, which cause frontotemporal dementia and motor neuron disease. It concerns those conditions, not Alzheimer's disease, and does not test any treatment, cure, or prevention for Alzheimer's.
Study details
- Evidence strengthModerate
How this study scored 54/100
Published in a leading specialty 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 | 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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 347 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.1 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 17.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 2 / 4 | Cited 43 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 | 1 / 3 | University of British Columbia: institution h-index 1,424 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24096617) |
| 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
- DOI: 10.1007/s00401-013-1181-y
- PubMed: 24096617
- Original source →
- Free full text: cIRcle (University of British Columbia) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Mackenzie, I. R., Arzberger, T., Kremmer, E., Troost, D., Lorenzl, S., Mori, K., et al. (2013). Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations. Acta neuropathologica. https://doi.org/10.1007/s00401-013-1181-y
Vancouver
Mackenzie IR, Arzberger T, Kremmer E, Troost D, Lorenzl S, Mori K, et al. Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations. Acta neuropathologica. 2013. doi:10.1007/s00401-013-1181-y. PMID: 24096617.
BibTeX
@article{mackenzie2013-24096617,
author = {Mackenzie, I. R. and Arzberger, T. and Kremmer, E. and Troost, D. and Lorenzl, S. and Mori, K. and Weng, S. M. and Haass, C. and others},
title = {{Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations}},
journal = {Acta neuropathologica},
year = {2013},
doi = {10.1007/s00401-013-1181-y},
pmid = {24096617},
url = {https://doi.org/10.1007/s00401-013-1181-y}
}
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