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Plasma immune signatures associate with neurodegeneration in frontotemporal lobar degeneration
van Schaik M, Lai KO, Shapiro NL, Jäck A, Goddard J, Crook H, Frohn R, Jones PS et al.. medRxiv, 2026-09-29
Topic: Inflammation, microglia and astrocytes
In exploratory full-cohort models, the multivariate CNS signature achieved an area under the curve of 0.93, compared with 0.82 for the multivariate inflammation signature. However, inflammatory proteins provided stronger discrimination for selected syndrome comparisons, including PPA versus PSP. Higher CD276 and SPP1 were associated with increased mortality, whereas higher amyloid-β42 was associated with lower mortality. A multivariate protein signature weighted towards tumour necrosis factor and immune signalling was associated with lower regional brain volumes across predominantly frontotemporal and limbic regions (canonical correlation 0.43; permutation p=0.018).
Key findings
- In exploratory full-cohort models, the multivariate CNS signature achieved an area under the curve of 0.93, compared with 0.82 for the multivariate inflammation signature.
- However, inflammatory proteins provided stronger discrimination for selected syndrome comparisons, including PPA versus PSP.
- Higher CD276 and SPP1 were associated with increased mortality, whereas higher amyloid-β42 was associated with lower mortality.
- A multivariate protein signature weighted towards tumour necrosis factor and immune signalling was associated with lower regional brain volumes across predominantly frontotemporal and limbic regions (canonical correlation 0.43; permutation p=0.018).
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Study details
- Study designcase-control study
- Participants177
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 42 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on 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 26 of the 62 points we could judge it on, which is 42 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 177 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 26 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 26 of the 62 points we could judge it on is 42 out of 100. |
| Total | 42 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
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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
van Schaik, M., Lai, K. O., Shapiro, N. L., Jäck, A., Goddard, J., Crook, H., et al. (2026). Plasma immune signatures associate with neurodegeneration in frontotemporal lobar degeneration. medRxiv. https://doi.org/10.64898/2026.09.28.26364155
Vancouver
van Schaik M, Lai KO, Shapiro NL, Jäck A, Goddard J, Crook H, et al. Plasma immune signatures associate with neurodegeneration in frontotemporal lobar degeneration. medRxiv. 2026. doi:10.64898/2026.09.28.26364155.
BibTeX
@article{vanschaik2026-b4bfc569,
author = {van Schaik, M. and Lai, K. O. and Shapiro, N. L. and Jäck, A. and Goddard, J. and Crook, H. and Frohn, R. and Jones, P. S. and others},
title = {{Plasma immune signatures associate with neurodegeneration in frontotemporal lobar degeneration}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.09.28.26364155},
url = {https://doi.org/10.64898/2026.09.28.26364155}
}
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