<i>In vivo</i> assessment of astrocyte reactivity in patients with progressive supranuclear palsy
Notice bibliographique
Résumé
Abstract Emerging evidence highlights the association of reactive astrocytes with neurodegenerative diseases. Although astrocytic pathology is a pathological hallmark of progressive supranuclear palsy (PSP), its role in the pathophysiology of the disease is not fully understood. In this study, we aimed to assess astrocyte reactivity in vivo in patients with PSP using magnetic resonance spectroscopy and plasma biomarkers. Furthermore, given the central role of astrocytes in brain energy metabolism and their glycolytic profile, which implies a preference for lactate production, we investigated alterations in brain energy metabolism by measuring brain lactate levels and examined their relationship with astrocyte reactivity. We included 30 patients with PSP-Richardson’s syndrome and 30 healthy controls; in patients, tau deposition was confirmed via 18 F-florzolotau-PET. Myo-inositol, an astroglial marker, and lactate were quantified in the anterior cingulate cortex (ACC) via magnetic resonance spectroscopy. The ACC was studied because previous functional imaging studies revealed its involvement as a distinctive feature of PSP. It involves in cognitive processes, such as executive function, which often exhibit deficits in patients with PSP. We measured plasma concentrations of glial fibrillary acidic protein (GFAP) as another astrocytic marker, neurofilament light chain (NfL), and tau phosphorylated at threonine 181. Reactive astrocytes, tau deposition, and synaptic loss in the ACC were assessed in post-mortem brain samples from another three patients with PSP with comparable disease durations to those of participants. The level of myo-inositol in the ACC and the plasma GFAP were significantly higher in patients than in healthy controls; these increases were significantly associated with Frontal Assessment Battery and Mini-Mental State Examination scores, respectively. The lactate level in the ACC was high in patients and correlated significantly with high myo-inositol levels. The plasma NfL outperformed other biomarkers in discriminating patients from controls (area under the curve [AUC] = 0.95), followed by lactate and myo-inositol (AUC = 0.88 and 0.78, respectively). Histological analysis of the ACC in patients revealed evident reactive astrocytes despite mild tau deposition and no marked synaptic loss. We found high levels of astrocyte biomarkers (myo-inositol in the ACC and plasma GFAP) in patients with PSP, suggesting astrocyte reactivity, and these biomarkers correlated with cognitive decline. Elevated myo-inositol levels were associated with high lactate levels, suggesting a link between reactive astrocytes and brain energy metabolism changes. Our results indicate that astrocyte reactivity in the ACC precedes pronounced tau pathology and neurodegenerative processes in the region and affects brain function in PSP.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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 | 0,001 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».