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Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease
Palmqvist S, Insel PS, Stomrud E, Janelidze S, Zetterberg H, Brix B, Eichenlaub U, Dage JL et al.. EMBO molecular medicine, 2019-11-11
Topic: Plasma and spinal-fluid biomarkers
Failures in Alzheimer's disease (AD) drug trials highlight the need to further explore disease mechanisms and alterations of biomarkers during the development of AD. Using cross-sectional data from 377 participants in the BioFINDER study, we examined seven cerebrospinal fluid (CSF) and six plasma biomarkers in relation to β-amyloid (Aβ) PET uptake to understand their evolution during AD. In CSF, Aβ42 changed first, closely followed by Aβ42/Aβ40, phosphorylated-tau (P-tau), and total-tau (T-tau). CSF neurogranin, YKL-40, and neurofilament light increased after the point of Aβ PET positivity. The findings were replicated using Aβ42, Aβ40, P-tau, and T-tau assays from five different manufacturers. Changes were seen approximately simultaneously for CSF and plasma biomarkers. Overall, plasma biomarkers had smaller dynamic ranges, except for CSF and plasma P-tau which were similar. In conclusion, using state-of-the-art biomarkers, we identified the first changes in Aβ, closely followed by soluble tau. Only after Aβ PET became abnormal, biomarkers of neuroinflammation, synaptic dysfunction, and neurodegeneration were altered. These findings lend in vivo support of the amyloid cascade hypotheses in humans.
Key findings
- Overall, plasma biomarkers had smaller dynamic ranges, except for CSF and plasma P-tau which were similar.
- In conclusion, using state-of-the-art biomarkers, we identified the first changes in Aβ, closely followed by soluble tau.
- These findings lend in vivo support of the amyloid cascade hypotheses in humans.
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Study details
- Study designcross-sectional
- Participants377
- Evidence strengthLow
How this study scored 57/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in 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 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EMBO molecular medicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 377 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 31709776) |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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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
Palmqvist, S., Insel, P. S., Stomrud, E., Janelidze, S., Zetterberg, H., Brix, B., et al. (2019). Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease. EMBO molecular medicine. https://doi.org/10.15252/emmm.201911170
Vancouver
Palmqvist S, Insel PS, Stomrud E, Janelidze S, Zetterberg H, Brix B, et al. Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease. EMBO molecular medicine. 2019. doi:10.15252/emmm.201911170. PMID: 31709776.
BibTeX
@article{palmqvist2019-31709776,
author = {Palmqvist, S. and Insel, P. S. and Stomrud, E. and Janelidze, S. and Zetterberg, H. and Brix, B. and Eichenlaub, U. and Dage, J. L. and others},
title = {{Cerebrospinal fluid and plasma biomarker trajectories with increasing amyloid deposition in Alzheimer's disease}},
journal = {EMBO molecular medicine},
year = {2019},
doi = {10.15252/emmm.201911170},
pmid = {31709776},
url = {https://doi.org/10.15252/emmm.201911170}
}
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