Uncovering atrophy progression pattern and mechanisms in individuals at risk of Alzheimer's disease
Notice bibliographique
Résumé
Alzheimer's disease is associated with pre-symptomatic changes in brain morphometry and accumulation of abnormal tau and amyloid-beta pathology. Studying the development of brain changes prior to symptoms onset may lead to early diagnostic biomarkers and a better understanding of Alzheimer's disease pathophysiology. Alzheimer's disease pathology is thought to arise from a combination of protein accumulation and spreading via neural connections, but how these processes influence brain atrophy progression in the pre-symptomatic phases remains unclear. Individuals with a family history of Alzheimer's disease (FHAD) have an elevated risk of Alzheimer's disease, providing an opportunity to study the pre-symptomatic phase. Here, we used structural MRI from three databases (Alzheimer's Disease Neuroimaging Initiative, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease and Montreal Adult Lifespan Study) to map atrophy progression in FHAD and Alzheimer's disease and assess the constraining effects of structural connectivity on atrophy progression. Cross-sectional and longitudinal data up to 4 years were used to perform atrophy progression analysis in FHAD and Alzheimer's disease compared with controls. PET radiotracers were also used to quantify the distribution of abnormal tau and amyloid-beta protein isoforms at baseline. We first derived cortical atrophy progression maps using deformation-based morphometry from 153 FHAD, 156 Alzheimer's disease and 116 controls with similar age, education and sex at baseline. We next examined the spatial relationship between atrophy progression and spatial patterns of tau aggregates and amyloid-beta plaques deposition, structural connectivity and neurotransmitter receptor and transporter distributions. Our results show that there were similar patterns of atrophy progression in FHAD and Alzheimer's disease, notably in the cingulate, temporal and parietal cortices, with more widespread and severe atrophy in Alzheimer's disease. Both tau and amyloid-beta pathology tended to accumulate in regions that were structurally connected in FHAD and Alzheimer's disease. The pattern of atrophy and its progression also aligned with existing structural connectivity in FHAD. In Alzheimer's disease, our findings suggest that atrophy progression results from pathology propagation that occurred earlier, on a previously intact connectome. Moreover, a relationship was found between serotonin receptor spatial distribution and atrophy progression in Alzheimer's disease. The current study demonstrates that regions showing atrophy progression in FHAD and Alzheimer's disease present with specific connectivity and cellular characteristics, uncovering some of the mechanisms involved in pre-clinical and clinical neurodegeneration.
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 | 0,005 |
| 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 | 0,002 |
| 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 ».