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Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals
Brum WS, Ashton NJ, Simrén J, di Molfetta G, Karikari TK, Benedet AL, Zimmer ER, Lantero-Rodriguez J et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023-11-20
Topic: Plasma and spinal-fluid biomarkers
Introduction Blood biomarkers have proven useful in Alzheimer's disease (AD) research. However, little is known about their biological variation (BV), which improves the interpretation of individual-level data. Methods We measured plasma amyloid beta (Aβ42, Aβ40), phosphorylated tau (p-tau181, p-tau217, p-tau231), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) in plasma samples collected weekly over 10 weeks from 20 participants aged 40 to 60 years from the European Biological Variation Study. We estimated within- (CV I ) and between-subject (CV G ) BV, analytical variation, and reference change values (RCV). Results Biomarkers presented considerable variability in CV I and CV G . Aβ42/Aβ40 had the lowest CV I (≈ 3%) and p-tau181 the highest (≈ 16%), while others ranged from 6% to 10%. Most RCVs ranged from 20% to 30% (decrease) and 25% to 40% (increase). Discussion BV estimates for AD plasma biomarkers can potentially refine their clinical and research interpretation. RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions. Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls. Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability. Plasma neurofilament light chain and glial fibrillary acidic protein demonstrate high between-subject variation, the impact of which will depend on clinical context. Reference change values can potentially be useful in monitoring early disease progression and the safety/efficacy of interventions on an individual level. Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
Key findings
- Results Biomarkers presented considerable variability in CV I and CV G .
- RCVs might be useful for detecting significant changes between serial measurements when monitoring early disease progression or interventions.
- Highlights Plasma amyloid beta (Aβ42/Aβ40) presents the lowest between- and within-subject biological variation, but also changes the least in Alzheimer's disease (AD) patients versus controls.
- Plasma phosphorylated tau variants significantly vary in their within-subject biological variation, but their substantial fold-changes in AD likely limits the impact of their variability.
- Serial sampling revealed that unexpectedly high values in heathy individuals can be observed, which urges caution when interpreting AD plasma biomarkers based on a single test result.
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Study details
- Participants20
- Evidence strengthLow
How this study scored 55/100
Published in a leading specialty journal. Scored zero for study design, 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 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 20 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 37985230) |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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APA 7th
Brum, W. S., Ashton, N. J., Simrén, J., di Molfetta, G., Karikari, T. K., Benedet, A. L., et al. (2024). Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.13518
Vancouver
Brum WS, Ashton NJ, Simrén J, di Molfetta G, Karikari TK, Benedet AL, et al. Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.13518. PMID: 37985230.
BibTeX
@article{brum2024-37985230,
author = {Brum, W. S. and Ashton, N. J. and Simrén, J. and di Molfetta, G. and Karikari, T. K. and Benedet, A. L. and Zimmer, E. R. and Lantero-Rodriguez, J. and others},
title = {{Biological variation estimates of Alzheimer's disease plasma biomarkers in healthy individuals}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.13518},
pmid = {37985230},
url = {https://doi.org/10.1002/alz.13518}
}