Head‐to‐head trajectories of MK6240, Flortaucipir, and plasma <i>p</i> ‐tau217 as a function of Aβ
Bibliographic record
Abstract
BACKGROUND: Tau PET tracers present distinct binding characteristics that might influence their trajectories and relationship with other biomarkers along the AD continuum. In a head-to-head study, we investigated the relationship between the emergence of PET tracers MK6240 and Flortaucipir, and plasma p-tau217 abnormalities as a function of Aβ PET deposition. We further assessed the concordance between tau PET and plasma p-tau217 positivity and its relationship with cognitive scores. METHOD: We evaluated 352 individuals from the HEAD study (205 cognitively unimpaired and 147 cognitively impaired) with Aβ PET, MK6240 and Flortaucipir tau PET, and plasma p-tau217 (ALZpath) and GFAP (Quanterix) measures. Tau PET Braak regions, plasma p-tau217 trajectories were modeled as functions of Aβ burden (Centiloid scale) using the Lowess method. Biomarkers were z-scored anchored on young individuals (n = 19, < 28 years old) as anchors. Tau PET (Braak 1 region) and plasma p-tau217 were considered positive/abnormal when surpassing 2.5 z-score. RESULT: Among the tested markers, MK6240 was the earliest to show abnormality as a function of Centiloid, occurring at 22 Centiloids, followed by plasma p-tau217 at 38 Centiloid and Flortaucipir at Centiloid 56 (Figure 1). Tau PET and plasma p-tau217 positivity showed an overall high concordance (∼80% for both tracers; Figure 2). In MK6240 discordant cases, most individuals were MK6240+/p-tau217- (13.8%), while 6.6% were MK6240-/p-tau217+ (Figure 2A). For Flortaucipir, 15% of discordant cases were Flortaucipir-/p-tau217+, while 4.8% were Flortaucipir+/p-tau217- (Figure 2B). The discordant groups present higher Centiloid than the ptau217-/Tau- group and overall decreased scores in cognitive tests, except for p-tau217+/MK6240- group (Figure 3). CONCLUSION: MK6240 becomes abnormal at lower levels of Aβ burden compared to plasma p-tau217 and Flortaucipir. The relatively high prevalence of discordant tau PET positive or plasma p-tau217 positive and suggests that some individuals may show tau PET positivity first, while others may exhibit plasma p-tau217 positivity first. The distinct cognitive profiles of this groups suggest potential clinical relevance, warranting further investigation.
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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 | 0.000 | 0.001 |
| 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) | 0.002 | 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".