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CSF and plasma Aβ42/40 across Alzheimer's disease continuum: comparison of two ultrasensitive Simoa® assays targeting distinct amyloid regions
Wojdała AL, Bellomo G, Toja A, Gaetani L, Parnetti L, Chiasserini D.. Clinical chemistry and laboratory medicine, 2023-09-04
Topic: Amyloid, tau and blood-test diagnosis
Objectives Decreased cerebrospinal fluid (CSF) amyloid beta 42/40 ratio (Aβ42/40) is one of the core Alzheimer's disease (AD) biomarkers. Measurement of Aβ42/40 in plasma has also been proposed as a surrogate marker for amyloidosis, however the validity and the diagnostic performance of this biomarker is still uncertain. Here we evaluated two immunoassays targeting distinct regions of the amyloid peptides by (a) performing a method comparison in both CSF and plasma, and (b) assessing the diagnostic performance across the AD continuum. Methods We used N4PE and N3PA Simoa ® assays to measure Aβ42/40 in CSF and plasma of 134 patients: preclinical AD (pre-AD, n=19), mild cognitive impairment due to AD (MCI-AD, n=41), AD at the dementia stage (AD-dem, n=35), and a control group (CTRL, n=39). The N4PE includes a detector antibody targeting the amyloid N-terminus, while the N3PA uses a detector targeting amyloid mid-region. Results Method comparison of N4PE and N3PA assays revealed discrepancies in assessment of plasma Aβ42/Aβ40. While the diagnostic performance of the two assays did not significantly differ in CSF, in plasma, N4PE assay provided better accuracy for AD discrimination than N3PA assay (AUC AD-dem vs. CTRL 0.77 N4PE, 0.68 N3PA). Conclusions While both Aβ42/40 assays allowed for an effective discrimination between CTRL and different AD stages, the assay targeting amyloid N-terminal region provided the best diagnostic performance in plasma. Differences observed in technical and diagnostic performance of the two assays may depend on matrix-specific amyloid processing, suggesting that further studies should be carried to standardize amyloid ratio measurement in plasma.
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APA 7th
Wojdała, A. L., Bellomo, G., Toja, A., Gaetani, L., Parnetti, L., & Chiasserini, D. (2024). CSF and plasma Aβ42/40 across Alzheimer's disease continuum: comparison of two ultrasensitive Simoa® assays targeting distinct amyloid regions. Clinical chemistry and laboratory medicine. https://doi.org/10.1515/cclm-2023-0659
Vancouver
Wojdała AL, Bellomo G, Toja A, Gaetani L, Parnetti L, Chiasserini D. CSF and plasma Aβ42/40 across Alzheimer's disease continuum: comparison of two ultrasensitive Simoa® assays targeting distinct amyloid regions. Clinical chemistry and laboratory medicine. 2024. doi:10.1515/cclm-2023-0659. PMID: 37656487.
BibTeX
@article{wojdala2024-37656487,
author = {Wojdała, A. L. and Bellomo, G. and Toja, A. and Gaetani, L. and Parnetti, L. and Chiasserini, D.},
title = {{CSF and plasma Aβ42/40 across Alzheimer's disease continuum: comparison of two ultrasensitive Simoa® assays targeting distinct amyloid regions}},
journal = {Clinical chemistry and laboratory medicine},
year = {2024},
doi = {10.1515/cclm-2023-0659},
pmid = {37656487},
url = {https://doi.org/10.1515/cclm-2023-0659}
}
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Key findings
- Results Method comparison of N4PE and N3PA assays revealed discrepancies in assessment of plasma Aβ42/Aβ40.
- While the diagnostic performance of the two assays did not significantly differ in CSF, in plasma, N4PE assay provided better accuracy for AD discrimination than N3PA assay (AUC AD-dem vs.
- Differences observed in technical and diagnostic performance of the two assays may depend on matrix-specific amyloid processing, suggesting that further studies should be carried to standardize amyloid ratio measurement in plasma.
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Study details
- Participants19
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed 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 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Clinical chemistry and laboratory medicine) |
| 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 | 19 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 37656487) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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