Neuroinflammation-mediated YKL-40 correlates with tau pathology and predicts longitudinal cognitive impairment and brain atrophy in Alzheimer’s disease, with hypertensive dependency
Notice bibliographique
Résumé
Background: Neuroinflammation and hypertension are involved in Alzheimer's disease (AD). However, their independent and additive impacts on astrocytes and AD-related pathologies have not been fully explored. Hence, this study investigated whether the associations between astrocyte reactivity, measured by cerebrospinal fluid (CSF), Chitinase 3-like protein 1 (CHI3L1/YKL-40), and AD-related pathologies were mediated by neuroinflammation and whether these associations were modified by hypertension. We also investigated the influence of hypertension on the relationship between baseline levels of CSF YKL-40 and longitudinal changes in cognitive function and brain structures. Methods: This study analyzed 288 participants from the AD Neuroimaging Initiative (ADNI) database. Multivariate linear regression, interaction, and subgroup analyses were conducted to explore the interrelationship between CSF YKL-40, AD biomarkers, neuroinflammation, cognitive function, and brain structures. Causal mediation analyses with 10,000 bootstrapped iterations were performed, using CSF YKL-40 as the independent variable and AD-related pathologies as the dependent variables, to explore mediation effects of neuroinflammation. Linear mixed-effects models were employed to study the associations between CSF YKL-40 and longitudinal changes in cognitive function and brain structures. Results: Higher baseline CSF YKL-40 levels were correlated with higher p-tau, t-tau, and neuroinflammatory biomarkers (ICAM1, VCAM1, sTNFR1, and sTNFR2), but with lower entorhinal cortex volume. Interaction showed that hypertension had a moderating influence on the associations between CSF YKL-40 and p-tau and t-tau. The significant associations of CSF YKL-40 with p-tau and t-tau were partially mediated by neuroinflammatory biomarkers (ICAM1, VCAM1, sTNFR1, and sTNFR2) in the whole sample (proportions: 13.0%∼78.8%). Similarly, the partial mediation effects of VCAM1, sTNFR1, and sTNFR2 on the aforementioned associations also existed in hypertensive subgroup (proportions: 17.9%∼50.3%). Additionally, higher baseline levels of CSF YKL-40 predicted faster decline in cognitive performance and brain atrophy (volumes of whole brain, hippocampus, entorhinal cortex, and middle temporal lobe) in the whole sample. Notably, subgroup analyses showed that the associations between higher CSF YKL-40 and faster brain atrophy were pronounced in hypertensive individuals. Conclusion: These findings suggest that neuroinflammation may mediate the relationship between astrocyte reactivity, measured by CSF YKL-40, and AD-related pathologies, with significant hypertensive dependency. Furthermore, elevated baseline CSF YKL-40 levels accelerated cognitive decline and brain atrophy, particularly in hypertensive individuals.
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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 | 0,001 |
| 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 ».