P2‐037: THE QUEST FOR EARLY REVERSIBLE CHANGES IN ALZHEIMER'S DISEASE: MASS SPECTROMETRIC IMAGING OF GANGLIOSIDES IN A NOVEL TRANSGENIC RAT MODEL OF PRODROMAL AD
Notice bibliographique
Résumé
Identifying the earliest cellular changes that lead to Alzheimer's disease (AD) is an important step towards preventing the disease. In search of such changes, we investigate membrane lipids called gangliosides that are essential for cell signaling and survival. The expression pattern of ganglioside species can change in response to stress, and in turn, altered membrane lipid composition can increase a cell's vulnerability to stressors. Gangliosides are implicated in a number of neurodegenerative diseases, including Alzheimer's disease (AD), yet whether gangliosides play an important role in the earliest stages of AD development remains unresolved. We hypothesize that changes in membrane lipid composition, including gangliosides, may be evident in the elderly brain during the prodromal stages of AD. Such membrane alterations may render the aging brain more vulnerable, and set in motion a downward spiral of pathologic events, culminating in the development of AD. llIdentifying the earliest cellular changes that lead to Alzheimer's disease (AD) is an important step towards preventing the disease. In search of such changes, we investigate membrane lipids called gangliosides that are essential for cell signaling and survival. The expression pattern of ganglioside species can change in response to stress, and in turn, altered membrane lipid composition can increase a cell's vulnerability to stressors. Gangliosides are implicated in a number of neurodegenerative diseases, including Alzheimer's disease (AD), yet whether gangliosides play an important role in the earliest stages of AD development remains unresolved. We hypothesize that changes in membrane lipid composition, including gangliosides, may be evident in the elderly brain during the prodromal stages of AD. Such membrane alterations may render the aging brain more vulnerable, and set in motion a downward spiral of pathologic events, culminating in the development of AD.the earliest cellular changes that lead to Alzheimer's disease (AD) is an important step towards preventing the disease. In search of such changes, we investigate membrane lipids called gangliosides that are essential for cell signaling and survival. The expression pattern of ganglioside species can change in response to stress, and in turn, altered membrane lipid composition can increase a cell's vulnerability to stressors. Gangliosides are implicated in a number of neurodegenerative diseases, including Alzheimer's disease (AD), yet whether gangliosides play an important role in the earliest stages of AD development remains unresolved. We hypothesize that changes in membrane lipid composition, including gangliosides, may be evident in the elderly brain during the prodromal stages of AD. Such membrane alterations may render the aging brain more vulnerable, and set in motion a downward spiral of pathologic events, culminating in the development of AD. To model the prodromal stage of AD in the elderly brain, we use a novel transgenic rat strain. APP21 transgenic (tg) rats express human APP Swe/Ind in high quantities but do not develop histological hallmarks of AD spontaneously as they age. Yet, these animals are susceptible to developing pathological hallmarks of AD when challenged, for example with AD brain extracts. In brain sections from APP21 tg animals, we imaged and profiled gangliosides based on their chemical structure using matrix-associated-laser-desorption/ionization imaging mass spectrometry (MALDI-IMS). This innovative technology allows us to visualize changes in ganglioside expression profiles within a neuroanatomical context, and to relate these profiles to neuropathological events. To test our hypothesis, we harvested brains from APP21 tg rats and age-matched wildtype rats at different ages. Brain sections were imaged with MALDI-IMS and screened histologically for any pathology related to AD (Abeta, plaques, astrogliosis, activated microglia). A comparison of brain ganglioside expression between APP21 tg rats and wildtype animals will be presented. If our hypothesis is confirmed, an intervention aimed at stabilizing membrane lipid composition in individuals at risk of developing AD may make the aging brain more resistant to neurodegenerative challenges.
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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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
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 ».