Rachelle Crescenzi1, 2, Catherine DeBrosse1, 2, Amy Thomas2, Mohammed Haris2, Hari Hariharan2, Virginia M. Y. Lee3, Arijitt Borthakur2, Ravinder Reddy2
1Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, United States; 2Center for Magnetic Resonance and Optical Imaging, Radiology, University of Pennsylvania, Philadelphia, PA, United States; 3Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States
Pathogenic tau protein aggregates in the synapses of neurons and disrupts neurotransmitter function. Glutamate is a wide-spread neurotransmitter, and has been shown by 1H MRS to decrease in the hippocampus of Alzheimers disease patients with tau pathology. In this study, we measured the concentration of glutamate by MRS and by chemical exchange saturation transfer (GluCEST) in healthy mice and transgenic mice with tau pathology. Mice with tau pathology have decreased concentrations of glutamate and n-acetyl-aspartate in their hippocampus. High resolution maps of glutamate concentration acquired with the novel GluCEST technique measured decreased glutamate across the entire brain of tauopathy mice.