Frontotemporal dementia (FTD) is a group of disorders caused by nerve cell loss in areas of the brain responsible for managing cognitive functions and voluntary movement. By itself, FTD, which is the second most common form of dementia after Alzheimer’s disease, can cause memory issues and attention problems, and impair cognitive flexibility — the ability to adapt thinking and behaviour to changing conditions. In the 1980s, it was believed that FTD rarely occurred in ALS, but scientists have recently discovered that it occurs more often and that these two diseases have many features in common. In fact, several studies suggest that ALS and FTD could be pooled together in one clinical spectrum of neurodegenerative disorders.

With ALS, FTD can cause mild symptoms that do not cause problems, noticeable changes in behaviour or cognitive processes involving comprehension and language abilities, or as in about 15 per cent of cases, it can appear as full dementia. Moreover, more and more studies have shown that ALS itself can lead to cognitive problems and about 50 to 60 percent of the ALS patients present some level of dementia.

The association between FTD and ALS is distressing for people facing an ALS diagnosis; however, the appearance and progression of FTD symptoms are providing new clues about the nature of ALS. Dr. Flavio Beraldo, an Adjunct Professor at the Department of Physiology and Pharmacology and a research associate at the Robarts Research Institute at Western University in London, Ontario has been studying the biological mechanisms of neurodegenerative diseases in genetically modified mice since 2008. His primary area of focus has been Alzheimer’s disease, but in the last two years, he has expanded his scope of work to include ALS.

Dr. Beraldo and his colleagues have successfully trained mice how to use an innovative touchscreen technology that can measure cognitive deficits. Here’s how it works: A mouse is placed into a compartment in a closed box that’s about the same size as a toaster oven and has a touchscreen wall like an iPad. The mouse learns to touch the correct image on the screen with its nose by receiving either a food reward for the right choice or a flash of light for the wrong decision. The system, called the Bussey-Saksida touchscreen chamber, is named after its inventors, Dr. Tim Bussey and Dr. Lisa Saksida at the Translational Cognitive Neuroscience Lab (TCNLab) at Western University. It uses software adapted from the Cambridge Neuropsychological Test Automated Battery (CANTAB), the gold standard tool used to evaluate human cognitive function.

Dr. Beraldo and two co-investigators, Dr. Marco Prado and Dr. Vania Prado recently received an ALS Canada Project Grant of $110,770 to use the touchscreen technology to investigate cognitive deficits in mice that have been genetically altered to have a human form of ALS. They will use mice that have been modified to overproduce TDP-43, a protein that is commonly found to be misfolded and clumped in over 95 per cent of human ALS cases and is also found in over half of FTD cases. The researchers will test the mice with tasks that evaluate attention, motivation/apathy, cognitive flexibility and memory as ALS pathology and motor deficits progress. Dr. Marco Prado is an expert in researching how abnormal protein behaviours lead to neurodegenerative diseases in mice and Dr. Vania Prado is an expert in generating genetically modified mice to understand the mechanisms of neurodegenerative diseases.

The touchscreen system is fully automated with electronic components that collect the data, so there is no possibility that human interaction by an experimenter might influence mice behaviour, a problem sometimes encountered in standard mice research. The box contains four separate compartments, allowing researchers to test four mice at a time. In total, 200-300 mice can be tested per day, a significant increase over the 50-60 mice per day that can be tested in standard mouse research where a researcher watches and records each mouse’s behaviour. Since the experimental tasks for mice are very similar to those used to test people, if this project is successful, the touchscreen technology could be easily adapted to test, in mice, potential new drugs that could be applied to human clinical trials in the future.

“We hope to detect cognitive impairment in TDP-43 mice and we anticipate that cognitive deficits will show up before motor deficits,” said Dr. Beraldo. “Ultimately, with a better understanding of the development and progression of cognitive deficits in mice, we may be able to diagnose ALS earlier and use touchscreen technology to screen drugs for future research.”

You can hear Dr. Beraldo speak about his research on January 24, 2018 (noon ET) during the first ALS Canada Research Program webinar of the year! Register now.

Dr. Beraldo’s project is one of 12 funded by the ALS Canada Research Program in 2017 following a rigorous scientific assessment by panels of global ALS experts. The panellists evaluated a larger pool of applications to identify the projects that are grounded in scientific excellence and have the potential to most quickly advance the field of ALS research in order to develop effective treatments.

ALS Canada is a registered charity that receives no government funding. Everything we do – from funding research to providing community-based support for people living with ALS – is possible only because of donor generosity and partnerships with provincial ALS Societies who contribute to the ALS Canada Research Program.

Posted in: Research