Exploring the Effects of Phospholipase A2 Inhibition on Brain Metabolism and Pathology in a Rat Model of Alzheimer’s Disease

Motivation: Current AD treatments do not improve cognitive deficits. Gaining a deeper understanding of the mechanisms underlying AD may reveal new therapeutic targets. Goal(s): Previous work demonstrated elevated choline levels in a preclinical model which may implicate the PLA2 pathway in AD. We aim to explore the role of PLA2 in AD. Approach: To understand the role of PLA2 in AD, we pharmacologically inhibited PLA2 in a preclinical model of AD. Metabolic, behavioural, and pathological aspects of AD were then explored using MRS, Barnes maze, immunostaining, and RNA sequencing. Results: Preliminary data indicate PLA2 inhibition reduces choline levels and improves long-term memory formation. Impact: This work may reveal PLA2 as new therapeutic target that improves cognitive deficits in Alzheimer’s disease. By linking behaviour, pathology, and metabolic processes, this study will give a well-rounded picture of how PLA2 activity impacts AD progression.