Abstract #3528

Inhibition of phospholipase A2 by mepacrine reduces total choline in a rat model of Alzheimer’s disease

Colleen Bailey¹, Ved Hatolkar¹, Wendy Oakden^1,2, Margaret M Koletar¹, JoAnne McLaurin^1,3, and Jamie Near^1,4

¹Sunnybrook Research Institute, Toronto, ON, Canada, ²Synaptive Medical, Toronto, ON, Canada, ³Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada, ⁴Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

Synopsis

Keywords: Alzheimer's Disease, Preclinical, neuronal lossWe examined the effect of the PLA2 inhibitor mepacrine on the levels of choline and other brain metabolites in the TgF344-AD rat model of Alzheimer's disease. Previous studies have demonstrated elevated levels of brain cholines in this model, similar to those observed in humans and attributed to increased membrane turnover. Total choline was higher in transgenic animals at baseline, but decreased following mepacrine treatment. Total choline also decreased in wildtype animals following treatment, consistent with the hypothesis that mepacrine reduces PLA2-mediated membrane turnover. Based on this finding, MRS choline measures may also serve as a biomarker for PLA2-mediated inflammatory processes.

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