RAVI S. PANDEY, United States of America
THE JACKSON LABAROTARY FOR GENOMIC MEDICINE CARTER LABAuthor Of 1 Presentation
CHARACTERIZATION OF GENETIC AND ENVIRONMENTAL INFLUENCES IN A NOVEL MOUSE MODEL OF LATE-ONSET AD
Abstract
Aims
Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder, with no effective treatment currently available. Although the vast majority of cases are late-onset AD (LOAD), current animal models do not recapitulate LOAD and thus are not ideal for the development of therapeutics. In addition to genetic factors, a western-style diet (e.g. high fat, high sugar, low vitamins) in combination with a sedentary lifestyle can lead to an increased risk for dementia. The MODEL-AD Center is charged with creating, defining, and distributing novel mouse models of LOAD for broad use.
Methods
MODEL-AD has created a mouse strain carrying a humanized ApoE4 knock-in mutation, an App allele with a humanized Aβ1-42 region in the mouse gene and an R47H point mutation of the Trem2 gene (B6.APOEe4/Trem2*R47H/hAβ). Cohorts of mice were aged to 4, 12, 18 and 24 months on standard or Western diet. Transcriptomics, biomarker and cognitive assays as well as immunohistochemistry and in vivo imaging studies were established to characterize these models and the effect of diet.
Results
Analyses of transcriptomic data in combination with behavioral and molecular phenotypes and in vivo imaging has yielded additional insight into genetic and environmental influences on AD endophenotypes and disease mechanisms.
Conclusions
The MODEL-AD consortium has established a new model to study the effects of genetic and environmental factors for LOAD. Furthermore, this model will serve as a backbone strain for the further addition of LOAD risk alleles to more closely align phenotypes in the mouse to outcomes observed in human AD.