Grant: Project Grant

Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases whose societal impacts are disastrous, and whose underlying biological origins are poorly understood. While AD and ALS differ in terms of clinical presentation, age of onset, and brain regions affected, they also share commonalities; both are associated with marked brain metabolic changes, including reduced levels of the neuronal marker NAA, and increased levels of choline containing metabolites (phosphocholine and glycerophosphocholine). These metabolic alterations can be detected using a non-invasive imaging technique called magnetic resonance spectroscopy (MRS) and reflect distinct aspects of the neurodegenerative process. Previous studies of altered metabolism in AD and ALS have focused on individual brain regions. Thus, it remains unknown whether altered brain metabolite levels in AD and ALS are focal or widespread. In 2025, Sunnybrook Research Institute installed a new ultra-high-field (7 Tesla) MRI system that is one of only three of its kind in Canada. This new MRI system will allow us to employ magnetic resonance spectroscopic imaging (MRSI) methods for mapping metabolite concentrations throughout the brain with unprecedented sensitivity and resolution. Leveraging this new state-of-the-art technology, the aims of this study are 1) to develop ultra-high field MRSI for mapping metabolic alterations throughout the brain; 2) to apply 7T MRSI to study patterns of altered brain metabolism in both AD and ALS patients; 3) to apply 7T MRSI to study sex differences in the patterns of altered brain metabolism in both AD and ALS patients; 4) to assess specific metabolic alterations associated with Alzheimer's disease risk genes; and 5) to assess specific metabolic alterations associated with ALS risk genes. This work will result in the development of cutting-edge metabolic imaging techniques and improved characterization of metabolic alterations in neurodegeneration.