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Abstract #4654

Hyperpolarized 13C MRS detects brain metabolic alterations in a tauopathy model of Alzheimer’s disease

Nicholas D. Vidas-Guscic1, Cassandra Leo1, Madison Heady1, Ashley Shaw1, Cornelius Von Morze1, Jason D. Ulrich2, Aisling Chaney1, and Caroline Guglielmetti1
1Department of Radiology, Washington University School of Medicine, Saint Louis, MO, United States, 2Department of Neurology, Washington University School of Medicine, Saint Louis, MO, United States

Synopsis

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas)

Motivation: Metabolic impairment is key in Alzheimer’s disease (AD) and metabolic imaging has high potential to improve AD diagnosis and monitoring.

Goal(s): Our goal is to assess whether hyperpolarized 13C MR spectroscopy (MRS) can detect glycolytic and oxidative metabolism alterations in AD.

Approach: Mice expressing mutant human tau (P301S) and human APOE4 (TE4 model), or expressing only human APOE4, underwent hyperpolarized 13C MRS and T2/T1-weighted MRI to investigate metabolic and volumetric changes.

Results: Hyperpolarized 13C MRS detects lower [13C]bicarbonate production in the tauopathy model, indicating impaired oxidative metabolism and mitochondrial dysfunction. T2/T1-weighted MRI confirmed brain neurodegeneration and blood-brain-barrier leakiness in this model.

Impact: We demonstrated that hyperpolarized 13C MRS has potential to monitor impaired oxidative metabolism in the brain of a clinically relevant AD model. Upon clinical translation, this method could improve diagnosis and monitoring of AD progression, and the assessment of therapies.

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