Plasma p-tau217 predicting brain-wide tau accumulation in preclinical AD
Bibliographic record
Abstract
BACKGROUND: Recently developed blood test of Alzheimer's disease (AD) has been recognized as a promising alternative to CSF and PET, as it is noninvasive, cost-effective, and more accessible. Particularly, plasma p-tau217 shows high sensitivity in detecting β-amyloid (Aβ) and tau positivity in early AD. However, the potential value of p-tau217 in revealing Aβ and tau distribution and predicting future development has not been studied. OBJECTIVES: We investigated the dose-response associations between p-tau217 and regional Aβ and tau measured by PET, as well as the longitudinal prediction of p-tau217 for prospective Aβ and tau accumulation measured by longitudinal PET. DESIGN: Cross-sectional and longitudinal analyses. SETTING: We used data in Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) study (N = 333) for primary analyses and Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 410) for validation. PARTICIPANTS: Cognitively unimpaired older adults (N = 333) from A4 study and cognitively unimpaired older adults (N = 222), mild cognitive impairment (N = 114), and dementia (N = 74) from ADNI. MEASUREMENTS: Flortaucipir PET measured regional Aβ and tau. RESULTS: Plasma p-tau217 was associated with concurrent Aβ in most cortical regions and tau in temporo-parietal cortices. Longitudinally, p-tau217 predicted brain-wide tau accumulation in widespread cortical regions in preclinical AD, but not Aβ change anywhere. CONCLUSIONS: Plasma p-tau217 shows dose-response, brain-wide relationships with concurrent Aβ and future tau development in preclinical AD, suggesting its potential in disease trajectory monitoring and large-scale screening for individuals approaching certain biological stages of AD in clinical trials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".