Imaging of Glutamate Alterations in Alzheimers Disease

Mohammad Haris¹, Kavindra Nath², Kejia Cai¹, Anup Singh¹, Rachelle Crescenzi¹, Feliks Kogan¹, Gaurav Verma², Sanjana Reddy¹, Hari Hariharan¹, Elias R. Melhem, Ravinder Reddy¹

Glutamate (Glu) is a major excitatory neurotransmitter in brain and has been shown to decrease in the early stages of Alzheimers disease (AD). Using glutamate amine exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in APP-PS1 transgenic mouse model of AD at high spatial resolution. Compared to wild-type controls, AD mice exhibited notable reduction of GluCEST contrast (~30%). A positive correlation was observed between GluCEST contrast and 1HMRS measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for diagnosing the disease in preclinical stages and enables the development of disease modifying therapies for AD.