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High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis
Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC et al.. Neurology, 2019-08-01
Topic: Amyloid, tau and blood-test diagnosis
Objective We examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards. Methods Using an immunoprecipitation and liquid chromatography-mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan. Results Plasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82-0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79-0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90-0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 ( p = 0.01). Conclusions Plasma Aβ42/Aβ40, especially when combined with age and APOE ε4 status, accurately diagnoses brain amyloidosis and can be used to screen cognitively normal individuals for brain amyloidosis. Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Plasma Aβ42/Aβ40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia. Classification of evidence This study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.
Key findings
- Results Plasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82-0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79-0.92).
- Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive.
Why it matters
In 158 mostly cognitively normal people, a mass-spectrometry blood test of the Aβ42/Aβ40 ratio matched amyloid PET brain-scan results well (AUC 0.88), and better when combined with age and APOE ε4 status (AUC 0.94). People whose PET scan was negative but whose blood ratio was abnormal were more likely to turn PET-positive later; the record does not give how much more likely. The authors propose it for screening research volunteers, such as for prevention trials. It detects amyloid build-up, not dementia, and it is not a treatment.
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Study details
- Effect sizeAUC 0.85; AUC 0.94
- Evidence strengthLow
Limitations
The comparison group was mostly cognitively normal, and samples were collected within 18 months of the PET scan, so this doesn't establish how the blood test performs once people already have symptoms or over longer time gaps.
How this study scored 62/100
Published in a leading specialty journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it. We have no data on institution's track record, so that was left out: it earned 60 of the 97 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| 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 | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 889 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 98.8 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 6 / 6 | Cited 61.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 91 other studies in this library |
| Still being cited | 4 / 4 | Cited 409 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Randall John Bateman: h-index 101 (OpenAlex, whole career) |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 0 institution(s) in 0 countries — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31371569) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 60 / 97 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 60 of the 97 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000008081
- PubMed: 31371569
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Schindler, S. E., Bollinger, J. G., Ovod, V., Mawuenyega, K. G., Li, Y., Gordon, B. A., et al. (2019). High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. https://doi.org/10.1212/wnl.0000000000008081
Vancouver
Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019. doi:10.1212/wnl.0000000000008081. PMID: 31371569.
BibTeX
@article{schindler2019-31371569,
author = {Schindler, S. E. and Bollinger, J. G. and Ovod, V. and Mawuenyega, K. G. and Li, Y. and Gordon, B. A. and Holtzman, D. M. and Morris, J. C. and others},
title = {{High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis}},
journal = {Neurology},
year = {2019},
doi = {10.1212/wnl.0000000000008081},
pmid = {31371569},
url = {https://doi.org/10.1212/wnl.0000000000008081}
}
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