Systemic inflammasome activation and pyroptosis associate with the progression of amnestic mild cognitive impairment and Alzheimer’s disease
Notice bibliographique
Résumé
BACKGROUND: Growing evidence indicates that inflammasome-mediated inflammation plays important roles in the pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Pyroptosis induced by inflammasome, and Gasdermin D (GSDMD) is involved in several neurodegenerative disorders. However, it is not clear whether peripheral inflammasome and pyroptosis are activated in aMCI and AD patients, influencing on neuroinflammation. The aim of this study was to examine the association between systemic inflammasome-induced pyroptosis and clinical features in aMCI and AD. METHODS: A total of 86 participants, including 33 subjects with aMCI, 33 subjects with AD, and 20 cognitively normal controls, in this study. The Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale were used for cognitive assessment. Levels of inflammasome-related genes/proteins in peripheral blood mononuclear cells (PBMCs) were determined using quantitative polymerase chain reaction and Western blotting. The levels of IL-1β, Aβ1-42, Aβ1-40, p-tau, and t-tau in cerebrospinal fluid (CSF), as well as the plasma IL-1β level, were measured by enzyme-linked immunosorbent assay. Finally, lipopolysaccharides (LPS) were used to investigate the effects of systemic inflammasome-induced pyroptosis in an AD mice model. RESULTS: Several genes involved in the inflammatory response were enriched in PBMCs of AD patients. The mRNA and protein levels of NLRP3, caspase-1, GSDMD, and IL-1β were increased in PBMCs of aMCI and AD patients. The IL-1β level in plasma and CSF of aMCI and AD patients was significantly higher than that in controls and negatively correlated with the CSF Aβ1-42 level, as well as MMSE and MoCA scores. Furthermore, there was a positive correlation between the IL-1β level in plasma and CSF of aMCI or AD patients. In vivo experiments showed that systemic inflammasome-induced pyroptosis aggravated neuroinflammation in 5 × FAD mice. CONCLUSIONS: Our findings showed that canonical inflammasome signaling and GSDMD-induced pyroptosis were activated in PBMCs of aMCI and AD patients. In addition, the proinflammatory cytokine IL-1β was strongly associated with the pathophysiology of aMCI and AD. As such, targeting inflammasome-induced pyroptosis may be a new approach to inhibit neuroinflammation in aMCI and AD patients.
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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 | 0,000 |
| 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 ».