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Plasma phosphorylated tau 217 detects amyloid-β in neuronal synuclein disease
Alena M Smith, Sara A Lorkiewicz, Burak Arslan, Laia Montoliu-Gaya, Nicholas J Ashton, Edward N Wilson, Daniel Alcolea, Íñigo Rodríguez-Baz et al.. NPJ Parkinson's disease, 2026-04-10
Topic: Plasma and spinal-fluid biomarkers
Multiple proteinopathies commonly coexist in neurodegenerative diseases, making it essential to evaluate plasma biomarker performance in these complex diseases. While plasma biomarkers accurately detect amyloid-β pathology in Alzheimer's disease (AD), their performance is unknown in neuronal synuclein disease (NSD). We aimed to determine the accuracy of plasma pTau217, pTau181, Aβ42/40, GFAP, and NfL to detect amyloid-β in NSD, then establish and validate cut points for the most promising marker. We included 253 participants (180 discovery; 73 validation). In the discovery cohort, NSD status was defined by CSF α-synuclein seed amplification assay and amyloid-β status by CSF Aβ42/40. Participants included individuals with clinical Lewy body disease (LBD), AD, and cognitively unimpaired. Validation cohorts consisted of clinically diagnosed LBD participants. In the discovery cohort, plasma pTau217, pTau181, Aβ42/40, and GFAP significantly differed by amyloid-β status regardless of NSD status, while NfL was highest in NSD+/Aβ+ participants. Among all biomarkers, plasma pTau217 showed the best diagnostic performance (AUC = 0.92, 95% CI = 0.81-0.98). Applying plasma pTau217 cut points to pre-screen clinically diagnosed LBD participants reduced the need for confirmatory amyloid-β PET or CSF in 41-56%. These findings support plasma pTau217 as a minimally-invasive tool for identifying pathological amyloid-β in neuronal synucleinopathies with mixed Alzheimer's disease pathology.
Key findings
- In the discovery cohort, plasma pTau217, pTau181, Aβ42/40, and GFAP significantly differed by amyloid-β status regardless of NSD status, while NfL was highest in NSD+/Aβ+ participants.
- These findings support plasma pTau217 as a minimally-invasive tool for identifying pathological amyloid-β in neuronal synucleinopathies with mixed Alzheimer's disease pathology.
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Study details
- Participants253
- Effect sizeAUC = 0.92
- Evidence strengthModerate
How this study scored 63/100
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, multi-centre collaboration and free to read, so those were left out: it earned 35 of the 56 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (NPJ Parkinson's disease) |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 253 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 41963316) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 35 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 35 of the 56 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Smith, A. M., Lorkiewicz, S. A., Arslan, B., Montoliu-Gaya, L., Ashton, N. J., Wilson, E. N., et al. (2026). Plasma phosphorylated tau 217 detects amyloid-β in neuronal synuclein disease. NPJ Parkinson's disease. https://doi.org/10.1038/s41531-026-01341-8
Vancouver
Smith AM, Lorkiewicz SA, Arslan B, Montoliu-Gaya L, Ashton NJ, Wilson EN, et al. Plasma phosphorylated tau 217 detects amyloid-β in neuronal synuclein disease. NPJ Parkinson's disease. 2026. doi:10.1038/s41531-026-01341-8. PMID: 41963316.
BibTeX
@article{smith2026-41963316,
author = {Smith, Alena M and Lorkiewicz, Sara A and Arslan, Burak and Montoliu-Gaya, Laia and Ashton, Nicholas J and Wilson, Edward N and Alcolea, Daniel and Rodríguez-Baz, Íñigo and others},
title = {{Plasma phosphorylated tau 217 detects amyloid-β in neuronal synuclein disease}},
journal = {NPJ Parkinson's disease},
year = {2026},
doi = {10.1038/s41531-026-01341-8},
pmid = {41963316},
url = {https://doi.org/10.1038/s41531-026-01341-8}
}
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