Home › Research › Biomarkers
Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease
Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P, Kornhuber J, Morris JC et al.. Journal of Alzheimer's disease : JAD, 2017-01-01
Topic: Plasma and spinal-fluid biomarkers
Background Decreased concentrations of amyloid-β 1-42 (Aβ42) in cerebrospinal fluid (CSF) and increased retention of Aβ tracers in the brain on positron emission tomography (PET) are considered the earliest biomarkers of Alzheimer's disease (AD). However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism. The CSF Aβ42/40 ratio seems to be a more accurate biomarker of clinical AD than CSF Aβ42 alone. Objective We tested whether CSF Aβ42 alone or the Aβ42/40 ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results. Methods CSF obtained from a mixed cohort (n = 200) of cognitively normal and abnormal research participants who had undergone amyloid PET within 12 months (n = 150 PET-negative, n = 50 PET-positive according to a previously published cut-off) was assayed for Aβ42 and Aβ40 using two recently developed immunoassays. Optimal CSF cut-offs for amyloid positivity were calculated, and concordance was tested by comparison of the areas under receiver operating characteristic (ROC) curves (AUC) and McNemar's test for paired proportions. Results CSF Aβ42/40 corresponded better than Aβ42 with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p < 0.0001) and a larger AUC (0.936 versus 0.814, respectively, p < 0.0001) associated with the ratio. For both CSF biomarkers, the percentage of CSF-abnormal/PET-normal cases was larger than that of CSF-normal/PET-abnormal cases. Conclusion The CSF Aβ42/40 ratio is superior to Aβ42 alone as a marker of amyloid-positivity by PET. We hypothesize that this increase in performance reflects the ratio compensating for general between-individual variations in CSF total Aβ.
Key findings
- However, a proportion of cases show discrepancies between the results of the two biomarker modalities which may reflect inter-individual differences in Aβ metabolism.
- Objective We tested whether CSF Aβ42 alone or the Aβ42/40 ratio corresponds better with amyloid PET status and analyzed the distribution of cases with discordant CSF-PET results.
- Results CSF Aβ42/40 corresponded better than Aβ42 with PET results, with a larger proportion of concordant cases (89.4% versus 74.9%, respectively, p < 0.0001) and a larger AUC (0.936 versus 0.814, respectively, p < 0.0001) associated with the ratio.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Participants200
- Effect size89.4%; 74.9%
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design 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 (Journal of Alzheimer's disease : JAD) |
| 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 | 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 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 200 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 27792012) |
| 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 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
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
Lewczuk, P., Matzen, A., Blennow, K., Parnetti, L., Molinuevo, J. L., Eusebi, P., et al. (2017). Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease. Journal of Alzheimer's disease : JAD. https://doi.org/10.3233/jad-160722
Vancouver
Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P, et al. Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease. Journal of Alzheimer's disease : JAD. 2017. doi:10.3233/jad-160722. PMID: 27792012.
BibTeX
@article{lewczuk2017-27792012,
author = {Lewczuk, P. and Matzen, A. and Blennow, K. and Parnetti, L. and Molinuevo, J. L. and Eusebi, P. and Kornhuber, J. and Morris, J. C. and others},
title = {{Cerebrospinal Fluid Aβ42/40 Corresponds Better than Aβ42 to Amyloid PET in Alzheimer's Disease}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2017},
doi = {10.3233/jad-160722},
pmid = {27792012},
url = {https://doi.org/10.3233/jad-160722}
}
Related studies in Biomarkers
Also tagged “18f”
319 studies in the library carry the topic tag “18f”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 319 tagged studies.