Concurrent Changes in Plasma Phosphorylated Tau 217, Tau PET, and Cognition in Preclinical Alzheimer Disease
Notice bibliographique
Résumé
Importance: Developing disease-modifying treatments is a priority for Alzheimer disease research. Objective: To determine the potential of plasma phosphorylated tau 217 (p-tau217) and tau positron emission tomography (PET) to assess disease modification in treatment trials. Design, Setting, and Participants: This diagnostic/prognostic study used longitudinal data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study collected from April 2014 to June 2023. Recruited from 67 sites in the US, Canada, Australia, and Japan, participants included older individuals (age 65-85 years) who were cognitively unimpaired at screening and underwent an amyloid PET scan. Participants without elevated amyloid PET were included from a companion to the A4 study, the Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. Exposure: 18F-florbetapir PET imaging. Main Outcomes and Measures: 18F-florbetapir PET imaging was used to classify participants as having elevated amyloid β (Aβ+). Measures of tau included longitudinal plasma p-tau217 and 18F-flortaucipir PET. Cognition was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Results: A total of 1169 individuals were included from A4 Study and 538 without elevated amyloid PET were included from the LEARN Study. Among these 1707 participants, the baseline mean (SD) age was 71.5 (4.7) years, 1024 (60%) were female, and 683 (40%) male; 1169 participants were Aβ+, and the mean (SD) Mini-Mental State Examination score was 28.8 (1.2). The tau PET substudy included 443 participants; plasma p-tau217 levels were available for 1643 participants. The largest effect size of longitudinal tau PET accumulation at 36 months in Aβ+ participants was in the inferior temporal gyrus. Baseline associations with longitudinal change in PACC score in Aβ+ participants were strongest in the entorhinal cortex (correlation [ρ] = -0.55; 95% CI, -0.63 to -0.45) and plasma p-tau217 levels (ρ = -0.47; 95% CI, -0.56 to -0.37). Tau PET changes in frontoparietal regions were strongly correlated with concurrent cognitive changes. Levels of plasma p-tau217 increased significantly in Aβ+ participants before showing significant deceleration (χ2 = 21.7; P < .001) and were not associated with concurrent cognitive change in the tau PET substudy (ρ = -0.03; 95% CI, -0.23 to 0.16) but were modestly associated with concurrent cognitive changes in the full plasma sample (n = 1119; ρ = -0.24; 95% CI, -0.34 to -0.14). Conclusions and Relevance: This study found that tau PET is valuable for both prognostic and real-time tracking of disease progression. Plasma p-tau217 predicts cognitive changes prior to overt cognitive impairment and can efficiently guide participant selection. Imaging-based tau measures may enhance detection of disease-modifying effects and refine therapeutic targets in future Alzheimer disease trials.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».