Keynote Presentation: Improving Research Translation in Dementia: Humanized Mouse Models, Cognition and Imaging with Live Q&A

Animal models present a unique opportunity to understand molecular mechanisms of pathological changes involved in cognitive dysfunction in neurological disorders. However, most of the work focusing on cognition in mice have yet to translate to new effective drugs in humans. First generation mouse models of Alzheimer’s disease have focused on transgenic expression of human genes, usually driven by neuronal promoters. Although these models have been informative to understand pathology, they failed to reproduce the subtle age and brain region relevant pathology observed in humans. Moreover, most of the analysis in this first-generation mouse models suffers from lack of translational approaches to investigate cognition and mesoscopic brain changes. Next-generation mouse models provide opportunities to understand the role of humanized genes in pathology and cognitive function. We are developing a fully translational platform for testing how these interactions manifest as cognitive and molecular changes and how translatable these are to human data. Touchscreen tests that are similar, and sometimes identical to human tests improve translational of cognitive function testing in health and disease. In parallel, we are optimizing in vivo imaging approaches routinely used in humans for parallel studies in mice. Given the automated and standardized approach of this platform, data can be organized and deposited in repositories (such as www.mousebytes.ca), facilitating open science goals. I will focus on our collaborative efforts to study the contribution misfolded and toxic alpha-synuclein for cognitive dysfunction and how risk factors in dementia affect cognition. I will also explore potential molecular mechanisms that can be used to develop new therapeutics in open translational science. This work provides a road map on how to improve reproducibility and predictive power of preclinical data to impact clinical outcomes. 

Learning Objectives:

1. Discuss approaches to integrate open science in pre-clinical research.

2. Discuss toxicity of misfolded proteins.

3. Discuss the principles of using high level cognitive tests to study dementia in animal models.