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

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.