Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

With age comes wisdom, or so they say. Yet, the reality is that with age, the ability to remember declines and for many progresses to the point where individuals are no longer self-sufficient. This is the experience for over 500,000 Canadians suffering from Alzheimer's disease (AD) and other forms of dementia. The AD endemic has been growing exponentially and is predicted to affect 150 million people by 2050. Moreover, these estimates do not include the countless silent sufferers dealing with the social, emotional, and financial turmoil associated with caring for loved ones stricken by this disease. AD progresses slowly, first robbing sufferers of their short-term memories, like where they left their keys, then wiping away their long-term memories, like the names of their loved ones, and finally taking away their ability to do simple daily tasks, like taking a shower. There is no cure for AD and little progress has been made to develop new treatments. Interestingly, 2/3 of AD patients are women who have a more aggressive disease progression. This suggests that understanding the differences between male and female brains could provide important clues to new therapeutic avenues. We will study how amyloid beta, a pathological agent in AD, disrupts neuronal health and function. We have exciting preliminary data suggesting that amyloid beta affects male and female brains differently, and these differences could lead to sex-specific therapies for men and women. Our research will focus on the role of calcium, an element that plays a vital role in maintaining neuronal health and whose regulation may differ between men and women. Our data indicate that modulating calcium is a powerful tool to reestablish neuronal function and maintain brain health. We hope to open the door towards new strategies and new treatments based on a better understanding of the underlying causes of AD.