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Plasma pTau 217/β-amyloid 1-42 ratio for enhanced accuracy and reduced uncertainty in detecting amyloid pathology
Natalya Benina, Luna Buitrago, Francesca I De Simone, Rachel R Radwan, M Craig Miller, Katie Martin, Diana Dickson, Sara Ho et al.. Brain : a journal of neurology, 2026-04-07
Topic: Plasma and spinal-fluid biomarkers
Plain-language summary
To improve clinical utility, a dual threshold approach was applied to maximize predictive values and positive likelihood ratios while minimizing the proportion of indeterminate results. When assessing the ability of individual plasma biomarkers to differentiate between amyloid-positive and amyloid-negative participants, plasma pTau217 (P < 0.001) and plasma Aβ1-42 (P = 0.0056) demonstrated significant discriminative power, whereas Aβ1-40 (P = 0.30) did not. Notably, the integration of these biomarkers into the plasma pTau217/Aβ1-42 ratio demonstrated enhanced classification performance (P < 0.001). Using a two-threshold approach based on positive and negative likelihood ratios (PLR/NLR) targets of 14/20, respectively, the plasma pTau217/Aβ1-42 ratio achieved a positive predictive value (PPV) of 94.44% and negative predictive value (NPV) of 94.28%, in the parametric model, comparable to plasma pTau217 alone (PPV: 94.44%, NPV: 94.28%), but yielded fewer indeterminate results (26.5% versus 38.6%). Using a non-parametric model, the plasma ratio achieved a PPV and NPV of 94.62% and 91.78%, respectively, while plasma pTau217 alone achieved 92.41% and 92.86%; the ratio once again reduced the proportion of indeterminate results (20.2% versus 35.1%). The plasma pTau217/Aβ1-42 ratio demonstrated superior performance in identifying amyloid pathology and reduced the frequency of indeterminate results compared to plasma pTau217 alone. These findings support the evaluation of the clinical utility of the plasma pTau217/Aβ1-42 ratio as a tool for identifying amyloid pathology in patients presenting with cognitive complaints.
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APA 7th
Benina, N., Buitrago, L., De Simone, F. I., Radwan, R. R., Miller, M. C., Martin, K., et al. (2026). Plasma pTau 217/β-amyloid 1-42 ratio for enhanced accuracy and reduced uncertainty in detecting amyloid pathology. Brain : a journal of neurology. https://doi.org/10.1093/brain/awag001
Vancouver
Benina N, Buitrago L, De Simone FI, Radwan RR, Miller MC, Martin K, et al. Plasma pTau 217/β-amyloid 1-42 ratio for enhanced accuracy and reduced uncertainty in detecting amyloid pathology. Brain : a journal of neurology. 2026. doi:10.1093/brain/awag001. PMID: 41562409.
BibTeX
@article{benina2026-41562409,
author = {Benina, Natalya and Buitrago, Luna and De Simone, Francesca I and Radwan, Rachel R and Miller, M Craig and Martin, Katie and Dickson, Diana and Ho, Sara and others},
title = {{Plasma pTau 217/β-amyloid 1-42 ratio for enhanced accuracy and reduced uncertainty in detecting amyloid pathology}},
journal = {Brain : a journal of neurology},
year = {2026},
doi = {10.1093/brain/awag001},
pmid = {41562409},
url = {https://doi.org/10.1093/brain/awag001}
}
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Key findings
- To improve clinical utility, a dual threshold approach was applied to maximize predictive values and positive likelihood ratios while minimizing the proportion of indeterminate results.
- When assessing the ability of individual plasma biomarkers to differentiate between amyloid-positive and amyloid-negative participants, plasma pTau217 (P < 0.001) and plasma Aβ1-42 (P = 0.0056) demonstrated significant discriminative power, whereas Aβ1-40 (P = 0.30) did not.
- Notably, the integration of these biomarkers into the plasma pTau217/Aβ1-42 ratio demonstrated enhanced classification performance (P < 0.001).
- Using a two-threshold approach based on positive and negative likelihood ratios (PLR/NLR) targets of 14/20, respectively, the plasma pTau217/Aβ1-42 ratio achieved a positive predictive value (PPV) of 94.44% and negative predictive value (NPV) of 94.28%, in the parametric model, comparable to plasma pTau217 alone (PPV: 94.44%, NPV: 94.28%), but yielded fewer indeterminate results (26.5% versus 38.6%).
- Using a non-parametric model, the plasma ratio achieved a PPV and NPV of 94.62% and 91.78%, respectively, while plasma pTau217 alone achieved 92.41% and 92.86%; the ratio once again reduced the proportion of indeterminate results (20.2% versus 35.1%).
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Study details
- Participants208
- Effect size94.44%; 94.28%; 26.5%
- Evidence strengthLow
How this study scored 61/100
Published in a leading specialty journal. Scored zero for study design and randomized / 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, multicenter collaboration and free to read, so those were left out: it earned 34 of the 56 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 208 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41562409) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 34 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 34 of the 56 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
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