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Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia
van der Ende EL, Xiao M, Xu D, Poos JM, Panman JL, Jiskoot LC, Meeter LH, Dopper EG et al.. Journal of neurology, neurosurgery, and psychiatry, 2020-04-09
Topic: Brain proteins, microglia and lab models
Introduction Synapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD. Methods We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN , C9orf72 or MAPT , and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses. Results Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage. Discussion We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.
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APA 7th
van der Ende, E. L., Xiao, M., Xu, D., Poos, J. M., Panman, J. L., Jiskoot, L. C., et al. (2020). Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp-2019-322493
Vancouver
van der Ende EL, Xiao M, Xu D, Poos JM, Panman JL, Jiskoot LC, et al. Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia. Journal of neurology, neurosurgery, and psychiatry. 2020. doi:10.1136/jnnp-2019-322493. PMID: 32273328.
BibTeX
@article{vanderende2020-32273328,
author = {van der Ende, E. L. and Xiao, M. and Xu, D. and Poos, J. M. and Panman, J. L. and Jiskoot, L. C. and Meeter, L. H. and Dopper, E. G. and others},
title = {{Neuronal pentraxin 2: a synapse-derived CSF biomarker in genetic frontotemporal dementia}},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2020},
doi = {10.1136/jnnp-2019-322493},
pmid = {32273328},
url = {https://doi.org/10.1136/jnnp-2019-322493}
}
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Key findings
- Results Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p<0.001) and non-carriers (990 pg/mL (597-1373), p<0.001) (corrected for age).
- Similar results were found for NPTX1 and NPTXR.
- Discussion We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD.
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Study details
- Study designlongitudinal study
- Participants106
- Evidence strengthModerate
How this study scored 66/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported 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 and multi-centre collaboration, so those were left out: it earned 38 of the 58 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 106 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 | — / 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 32273328) |
| Free to read | 2 / 2 | Free to read |
| Points | 38 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 38 of the 58 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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