Grant: Master's Award: Canada Graduate Scholarships

Alzheimer’s Disease (AD), a chronic neurodegenerative disease, affects approximately 660,000 Canadians, with this number predicted to triple by 2050 [1]. Emerging evidence suggests that cognitive decline in AD is closely related to the abnormal phosphorylation of tau proteins, forming clumps–called “tangles”–inside neurons. The hyperphosphorylated tau proteins (termed pre-tangles) are found in the brainstem of most by 20 years of age but do not progress to AD in all individuals. Nonetheless, there appears to be a significant intervention window in the development of AD. One novel therapy is the manipulation of the gut-brain axis via probiotic supplementation. Notably, AD and imbalances in the gut microbiome lead to increased Blood-Brain Barrier and intestinal barrier permeability, respectively. The result is a pathway for bacterial metabolites into the brain, promoting disease through neuroinflammation. Probiotic supplementation, however, fosters a balanced gut microbial composition. As a result, intestinal and brain barrier permeabilities are decreased, systemic inflammation is decreased, blood lipid profiles become healthier, and cellular signalling prevents tau hyperphosphorylation. It is not, however, known if probiotics start their benefits in pre-clinical AD. The present study, therefore, supplements probiotics in a pre-tangle rat model to better understand this connection. Specifically, we will assess behavioural effects, Blood-Brain Barrier integrity, systemic inflammation, blood lipid profiles, gut microbiome compositions, and sex differences in response to probiotic treatment. Ultimately, the aim is to provide a precedent for the use of probiotics to delay AD progression and to improve health outcomes in Canadians.