摘要
Sporadic late-onset Alzheimer’s disease(SLOAD)and familial early-onset Alzheimer’s disease(FEOAD)associated with dominant mutations in APP,PSEN1 and PSEN2,are thought to represent a spectrum of the same disorder based on near identical behavioral and histopathological features.Hence,FEOAD transgenic mouse models have been used in past decades as a surrogate to study SLOAD pathogenic mechanisms and as the gold standard to validate drugs used in clinical trials.Unfortunately,such research has yielded little output in terms of therapeutics targeting the disease’s development and progression.In this short review,we interrogate the widely accepted view of one,dimorphic disease through the prism of the Bmi1+/–mouse model and the distinct chromatin signatures observed between SLOAD and FEOAD brains.
基金
This work was supported by grants from the National Science and Engineering Research Council of Canada(NSERC)(to GB),Canadian Institutes of Health Research(CIHR)(to GB),Maisonneuve-Rosemont Hospital Foundation and Fondation de la Famille Pierre Theroux(to GB).RH is supported by a fellowship from the Maisonneuve-Rosemont Hospital Foundation.AF is supported by post-doctoral fellowship from the Jane Coffin Childs Fund.
