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Development and External Validation of a Plasma p-tau217-Based Model for MCI-to-Dementia Progression
Du, M.; Roy, I.; Chu, B.; Tian, S.. medRxiv (preprint), 2026-09-16
Topic: Brain proteins, microglia and lab models
--Clinical trajectories after a diagnosis of mild cognitive impairment (MCI) vary widely, so prognostic models must account for both the timing of subsequent diagnoses and unequal follow-up. Using the Alzheimers Disease Neuroimaging Initiative (ADNI), we developed a Cox proportional-hazards model for time from an MCI-aligned plasma index visit to a subsequent dementia diagnosis, using age at study entry and log-transformed plasma p-tau217. Coefficients and baseline survival were estimated in 401 participants with 85 events and then frozen and applied without refitting to an independent cohort from the National Alzheimers Coordinating Center (NACC). NACC p-tau217 measurements were reported on the Quanterix HD-X platform and were mapped to the ADNI development-assay scale using a prespecified transformation derived from paired ADNI measurements. The two-predictor model reached a pooled out-of-fold C-index of 0.775 in ADNI (apparent C-index, 0.778) and 0.652 (95% CI, 0.526-0.765) in 104 NACC participants with 25 incident dementia diagnoses. At two years, observed risk was 0.214 compared with a mean predicted risk of 0.089, an observed-to-expected ratio of 2.40. Neither adding APOE{varepsilon} 4 count, sex, or education nor expanding the model with GFAP, NfL, and the A{beta}42/A{beta}40 ratio materially improved discrimination in ADNI; APOE{varepsilon} 4 also provided no detectable incremental gain in NACC. The model showed moderate discrimination in NACC, although the wide confidence interval includes values near chance and the middle and higher risk tertiles did not clearly separate; C-indices were similar in the bridged primary and direct-scale sensitivity analyses, and mean two-year predicted risk was lower than observed only in the bridged analysis.
Key findings
- At two years, observed risk was 0.214 compared with a mean predicted risk of 0.089, an observed-to-expected ratio of 2.40.
- The model showed moderate discrimination in NACC, although the wide confidence interval includes values near chance and the middle and higher risk tertiles did not clearly separate; C-indices were similar in the bridged primary and direct-scale sensitivity analyses, and mean two-year predicted risk was lower than observed only in the bridged analysis.
Why it matters
This study built a model using age and a blood marker, p-tau217, to predict which people with mild cognitive impairment will develop dementia. The model worked moderately well in one group but its accuracy in a second group was uncertain, with a wide range that included near-chance results, so it is not yet ready for clinical use.
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Study details
- Participants401
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 26 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 24 of the 94 points we could judge it on, which is 26 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| 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 | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 401 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Alzheimer’s Disease Neuroimaging Initiative: h-index 3 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 24 of the 94 points we could judge it on is 26 out of 100. |
| Total | 26 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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. Check the citation against the original before you use it.
APA 7th
Du, M., Roy, I., Chu, B., & Tian, S. (2026). Development and External Validation of a Plasma p-tau217-Based Model for MCI-to-Dementia Progression. medRxiv (preprint). https://doi.org/10.64898/2026.09.15.26363045
Vancouver
Du M, Roy I, Chu B, Tian S. Development and External Validation of a Plasma p-tau217-Based Model for MCI-to-Dementia Progression. medRxiv (preprint). 2026. doi:10.64898/2026.09.15.26363045.
BibTeX
@article{du2026-54b6b226,
author = {Du, M. and Roy, I. and Chu, B. and Tian, S.},
title = {{Development and External Validation of a Plasma p-tau217-Based Model for MCI-to-Dementia Progression}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.09.15.26363045},
url = {https://doi.org/10.64898/2026.09.15.26363045}
}