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CNS-selective plasma p-tau217 accurately captures Alzheimer's disease pathology and progression
Xuemei Zeng, Marissa F Farinas, Michel N Nafash, Denis S Smirnov, Brian J Lopresti, Cristy Matan, Dana L Tudorascu, Sarah B Berman et al.. medRxiv : the preprint server for health sciences, 2026-05-21
Topic: Plasma and spinal-fluid biomarkers
Plain-language summary
Blood-based biomarkers have expanded access to biologically supported diagnosis of Alzheimer's disease (AD), particularly through measurement of amyloid-beta (Aβ) and phosphorylated tau species1-3. Among these, plasma tau phosphorylated at threonine 217 (p-tau217) is currently the leading biomarker recommended by clinical guidelines4-6. However, circulating p-tau217 originates from both central nervous system (CNS) and peripheral tissues7, potentially limiting specificity, particularly in individuals with common age-related comorbidities8. Here we report a next-generation biomarker, brain-derived p-tau217%, which quantifies the proportion of circulating tau that is CNS-derived and phosphorylated at threonine 217. Across neuropathologically defined, Aβ- and tau-neuroimaging-characterized, and memory clinic cohorts, brain-derived p-tau217% consistently identified AD pathology and clinical AD with larger effect sizes, higher discriminative accuracy, and improved sensitivity and specificity, outperforming conventional non-CNS-selective plasma p-tau217, p-tau217/Aβ1-42 and p-tau217% alternatives as well as brain-derived-p-tau217 alone. Furthermore, the CNS-selective biomarker demonstrated more robust prediction of future clinical progression in individuals followed for up to two decades. Importantly, diagnostic performance remained high in older adults with diabetes and cardiovascular disease, populations in which standard p-tau217 showed reduced specificity. Moreover, superiority extended to comparisons against multiple CNS disease-related proteins in targeted proteomic analyses. These findings establish plasma brain-derived p-tau217% as a biologically grounded and clinically robust biomarker that advances molecular definition, detection, and prognosis of Alzheimer's disease.
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APA 7th
Zeng, X., Farinas, M. F., Nafash, M. N., Smirnov, D. S., Lopresti, B. J., Matan, C., et al. (2026). CNS-selective plasma p-tau217 accurately captures Alzheimer's disease pathology and progression. medRxiv : the preprint server for health sciences. https://doi.org/10.64898/2026.05.18.26353208
Vancouver
Zeng X, Farinas MF, Nafash MN, Smirnov DS, Lopresti BJ, Matan C, et al. CNS-selective plasma p-tau217 accurately captures Alzheimer's disease pathology and progression. medRxiv : the preprint server for health sciences. 2026. doi:10.64898/2026.05.18.26353208. PMID: 42238423.
BibTeX
@article{zeng2026-42238423,
author = {Zeng, Xuemei and Farinas, Marissa F and Nafash, Michel N and Smirnov, Denis S and Lopresti, Brian J and Matan, Cristy and Tudorascu, Dana L and Berman, Sarah B and others},
title = {{CNS-selective plasma p-tau217 accurately captures Alzheimer's disease pathology and progression}},
journal = {medRxiv : the preprint server for health sciences},
year = {2026},
doi = {10.64898/2026.05.18.26353208},
pmid = {42238423},
url = {https://doi.org/10.64898/2026.05.18.26353208}
}
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Key findings
- Furthermore, the CNS-selective biomarker demonstrated more robust prediction of future clinical progression in individuals followed for up to two decades.
- These findings establish plasma brain-derived p-tau217% as a biologically grounded and clinically robust biomarker that advances molecular definition, detection, and prognosis of Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 23 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on 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 14 of the 60 points we could judge it on, which is 23 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv : the preprint server for health sciences) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 42238423) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 14 / 60 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 14 of the 60 points we could judge it on is 23 out of 100. |
| Total | 23 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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