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Abstract #4036

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

Emily Hiles1,2, Ved Hatolkar2, Colleen Bailey2, Wendy Oakden2, Tina Beckett2, Mary Brown2, JoAnne McLaurin2,3, and Jamie Near1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, 2Sunnybrook Research Institute, Toronto, ON, Canada, 3Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

Synopsis

Keywords: Alzheimer's Disease, Spectroscopy

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.

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