Longitudinal association between synaptic dysfunction and Alzheimer’s disease pathology in preclinical Alzheimer’s disease
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Notice bibliographique
Résumé
Abstract Background Synapse loss in Alzheimer’s disease (AD) is correlates closely with cognitive impairment. Recent evidence suggests that synapse loss is promoted by amyloid‐beta, leading in turn to the spread of tau pathology. We sought to assess: 1) the association in positron emission tomography (PET) between several cerebrospinal fluid (CSF) synaptic biomarkers and amyloid and tau burden, as well as their annual change; and 2) the potential clinical utility of these synaptic biomarkers in preclinical AD. Methods Mass spectrometry assays quantified cerebrospinal fluid (CSF) markers of synaptic dysfunction (GAP43, SYT1, SNAP25 and Neurogranin) on 75 older adults (age 67.1 ± 4.8 years, 69.3% female) from the PREVENT‐AD cohort. These persons also had longitudinal amyloid ([18F]‐NAV4694) and tau ([18F]‐AV1451) PET scans performed over approximately 4.5 years. All were cognitively unimpaired (CU) at baseline, but 19 developed mild cognitive impairment (MCI) during follow‐up. We examined: 1) the association between these synaptic dysfunction biomarkers and global Aβ and entorhinal tau burden as well as their annual change, adjusting for age and sex; and 2) synaptic biomarker differences across those with Aβ at baseline vs. those who subsequently developed such pathology, and between individuals who remained CU vs. those who developed MCI during follow‐up. Analyses were considered significant at p=0.05/5=0.01 to account for multiple comparisons. Results Amyloid burden was positively associated with increased SNAP25long, while tau burden was associated with all 5 synaptic biomarkers (Figure 1). No association was found between these markers and amyloid and tau annual change. GAP43 and SNAP25 differed in Aβ‐ and Aβ+ groups but showed no difference across amyloid accumulators’ groups (Figure 2). Finally, MCI individuals had higher SNAP25long and GAP43 concentration than CU individuals (Figure 3). Conclusions GAP43 and SNAP25, being markers associated with neuronal growth and synaptic vesicle fusion, appear closely related to amyloid and tau burden, but only at baseline, even in preclinical AD. These biomarkers of synapse loss appear also to have clinical relevance, with differences observed in MCI compared to CU individuals. Future studies should explore these biomarkers, alongside pathology reduction, as potential targets for AD prevention to confirm these preliminary findings.
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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 | 0,001 | 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 découle