Prognostic utility of <i>p</i> ‐tau217 and tau PET in Alzheimer's disease
Bibliographic record
Abstract
Abstract Background Recently proposed biomarker‐based biological staging schemes may improve risk prediction of cognitive impairment in Alzheimer's disease (AD). Evidence demonstrates that tau positron emission tomography (PET) reliably identifies individuals at high risk for clinical progression. While plasma phosphorylated tau at threonine 217 ( p ‐tau217) has been proposed as a cost‐effective biomarker, its added prognostic value to tau PET remains under‐explored. Here, we tested the utility of combining plasma p ‐tau217 and tau PET for predicting risk of clinical progression in cognitively unimpaired (CU) individuals. Method We evaluated 156 CU individuals from the A4 Study placebo group with positron emission tomography (PET) for amyloid‐β (Aβ) plaques ([ 18 F]Florbetapir) and tau tangles ([ 18 F]Flortaucipir), plasma p ‐tau217 and longitudinal neuropsychological testing. Aβ‐positive (A+) individuals were classified as p ‐tau217‐positive (A+T p‐tau217 +), tau PET‐positive in the medial temporal lobe (A+T MTL +) and in the neocortex (A+T NEO +). Cutpoints were determined as the mean + 2.0 standard deviations (SD) of the corresponding tau biomarker in Aβ‐negative controls from the LEARN substudy. Time‐to‐event analyses considered clinical progression as a 1 point increase in the Clinical Dementia Rating ‐ Sum of Boxes (CDR‐SB) score, and dichotomized A/T biomarkers were used as predictors. Result Demographics of the study population are reported in Table 1. Cox proportional‐hazard models showed a gradual increase in the risk of clinical progression in the A+T MTL + (HR=2.25, p = 0.0034) and A+T NEO + (HR=3.14, p < 0.0001) groups versus the A+ (reference) group. In analyses incorporating p ‐tau217 to the models, we found that the A+T p‐tau217 + group showed a significantly increased risk for clinical progression compared to A+ group when added to the T MTL model but not to the T NEO model. (Figure 1). Model fit indexes indicated that adding p ‐tau217 to the models improved the predictive performance of the T MTL model, but not of the T NEO model (Table 2). Conclusion We found that p ‐tau217 positivity does not lead to a clear added prognostic value to tau PET in assessing risk of clinical progression in individuals with preclinical AD, particularly when measuring neocortical tau PET signal. These findings support imaging biomarkers as the primary prognostic tools for predicting cognitive impairment in early AD stages.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".