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MODEL-AD: Late-Onset Alzheimer’s Disease Models
Poster Title: MODEL-AD: Late-Onset Alzheimer’s Disease Models
Submitted on 14 Aug 2018
Author(s): Bruce Lamb on behalf of the MODEL-AD Consortium
Affiliations: The Jackson Laboratory, Indiana University Stark Neuroscience Institute, Sage Bionetworks, University of California Irvine
This poster was presented at AAIC 2018
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Poster Information
Abstract: Alzheimer’s disease (AD) is the most common form of dementia, with no effective preventative strategies or treatments. A major obstacle when designing therapeutics to treat AD is the lack of predictive animal models in preclinical testing trials. One reason for this may be that existing models are based on familial mutations, which accounts for only 2-5% of all cases, while most AD cases are non-familial late-onset AD (LOAD). The Model Organism Development and Evaluation for Late-onset AD (MODEL-AD) Center has been established as a consortium consisting of Indiana University, The Jackson Laboratory, University of California-Irvine and Sage Bionetworks to create new animal models of LOAD with the end goal of identifying biomarkers and developing therapeutics to prevent AD.
The Bioinformatics and Data Management Core (BDMC) prioritizes novel sequence variants, creating analytical pipelines for human-mouse phenotype comparisons, and analyzing phenotypic data. The Disease Modeling Project (DMP) creates new mouse models based on variants identified by the BDMC. APOE4 and Trem2 alleles are the strongest genetic risk factors for LOAD; as such we have created a novel model expressing both human APOE4 and the R47H allele of Trem2. This is being phenotypically characterized using functional assays, neurodegeneration, amyloid and tau pathology, transcriptional and metabolic profiling, and in vivo imaging. The Preclinical Testing Core (PTC) evaluates novel compounds in new models with an AD-like phenotype based on a tertiary screening pipeline with predetermined go/no go criteria. These criteria include exposure levels in target tissues, target engagement, disease modifying effect, and in vivo functional activity and therapeutic index. All data will be made available through the Sage-Synapse portal. The Center goals are: to identify and prioritize novel genetic variants, genes and biomarkers from AD patient data; to generate and validate new animal models based on these LOAD variants; and to utilize these novel models in a preclinical testing paradigm. The APOE4/Trem2 model as well as a humanized Aß mouse will serve as standard backgrounds as additional LOAD genetic variants are introduced at IU/JAX/ UCI. Conclusions: All models, protocols, and data sets will be made widely available. For more information see
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