Cognitive assessment in TDP-43 ALS/FTD mouse models using automated touchscreen tasks – a translatable approach for drug development

A significant number of people with ALS also develop cognitive impairment that may include problems with language, thought processing and behavioural changes. A prominent protein called TDP-43 is associated with ALS and is also related to cognitive impairments in frontotemporal dementia. Over 95% of people with ALS have abnormal TDP-43 protein function. To date, researchers have not been able to effectively investigate cognitive impairment in ALS mice models with TDP-43 protein abnormalities as currently available tests for studying symptoms in ALS laboratory mice are not very sensitive and are prone to human error in measurement. Dr. Beraldo and colleagues are using a touchscreen system that resembles a box that uses iPads as the walls. By using food as a reward, they have trained mice to recognize images and touch the walls with their noses. In this project, the researchers will measure how well ALS mice complete the same tasks and hope to identify subtle levels of cognitive impairment compared to mice without ALS. The touchscreen system will allow the investigators to measure changes in cognitive impairment as motor neurons degenerate in ALS mice. If successful, this new technology could be used as a tool for measuring cognitive impairment in several other ALS mouse models or for screening drugs to find new treatments in the future.