Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Alzheimer's disease (AD) is commonly associated with behavioural changes such as agitation. Severe agitation is an important symptom to detect and treat as it increases the progression of AD, physical health problems, and caregiver stress. Biomarkers to detect AD severity exist, but biomarkers to detect behavioural symptoms in AD are still unknown. The production of harmful cells is elevated in the AD brain due to increased oxidative stress (OS), which creates a toxic environment and damages brain cells. Elevated OS has also been shown to increase brain cholesterol metabolism, resulting in increased harmful byproducts such as cerebrocholesterol (Cchol). Blood levels of Cchol provide a non-invasive measurement of altered brain cholesterol metabolism and has been shown to represent 90% of Cchol derived from the brain. Increased Cchol can be harmful in AD as it negatively impacts endocannbinoid system (ECS) signalling, which is important in regulating behavioural symptoms. These symptoms are common and difficult to treat in AD and currently prescribed medications, such as antipsychotics, have modest benefits which may not outweigh the associated harmful side effects. With the development of synthetic cannabinoids (CB) such as nabilone, which target the ECS, the safety and efficacy of CB can now be studied. CB have benefits on agitation and other behavioural symptoms, while also having neuroprotective effects on the AD brain by reducing inflammation and oxidative stress. Therefore, I propose to assess Cchol as a biomarker of agitation in moderate to severe AD patients, and of treatment response to nabilone. If successful, this study can help identify a previously unstudied biomarker, Cchol, and target agitated AD patients for treatment with nabilone.