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Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study
Emma L van der Ende, Carolin Heller, Aitana Sogorb-Esteve, Imogen J Swift, David McFall, Georgia Peakman, Arabella Bouzigues, Jackie M Poos et al.. Journal of neuroinflammation, 2022-09-05
Topic: Plasma and spinal-fluid biomarkers
CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers. In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers. In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP. In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores. Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD. Intriguingly, correlations with several disease measures in presymptomatic carriers suggest that complement protein levels might increase before symptom onset. Although the overlap between groups precludes their use as diagnostic markers, further research is needed to determine their potential to monitor dysregulation of the complement system in FTD.
Key findings
- CSF C1q and C3b, as well as plasma C2 and C3, were elevated in symptomatic mutation carriers compared to presymptomatic carriers and non-carriers.
- In genetic subgroup analyses, these differences remained statistically significant for C9orf72 mutation carriers.
- In presymptomatic carriers, several complement proteins correlated negatively with grey matter volume of FTD-related regions and positively with NfL and GFAP.
- In symptomatic carriers, correlations were additionally observed with disease duration and with Mini Mental State Examination and Clinical Dementia Rating scale® plus NACC Frontotemporal lobar degeneration sum of boxes scores.
- Elevated levels of CSF C1q and C3b, as well as plasma C2 and C3, demonstrate the presence of complement activation in the symptomatic stage of genetic FTD.
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Study details
- Study designcohort study
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 32 of the 56 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuroinflammation) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following people over time |
| 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 | 3 / 5 | 2022 — within 6 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36064709) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 32 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 32 of the 56 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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APA 7th
van der Ende, E. L., Heller, C., Sogorb-Esteve, A., Swift, I. J., McFall, D., Peakman, G., et al. (2022). Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study. Journal of neuroinflammation. https://doi.org/10.1186/s12974-022-02573-0
Vancouver
van der Ende EL, Heller C, Sogorb-Esteve A, Swift IJ, McFall D, Peakman G, et al. Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study. Journal of neuroinflammation. 2022. doi:10.1186/s12974-022-02573-0. PMID: 36064709.
BibTeX
@article{vanderende2022-36064709,
author = {van der Ende, Emma L and Heller, Carolin and Sogorb-Esteve, Aitana and Swift, Imogen J and McFall, David and Peakman, Georgia and Bouzigues, Arabella and Poos, Jackie M and others},
title = {{Elevated CSF and plasma complement proteins in genetic frontotemporal dementia: results from the GENFI study}},
journal = {Journal of neuroinflammation},
year = {2022},
doi = {10.1186/s12974-022-02573-0},
pmid = {36064709},
url = {https://doi.org/10.1186/s12974-022-02573-0}
}