Imaging of glutamate neurotransmitter alterations in Alzheimer's disease

• Published in: NMR in biomedicine Vol. 26; no. 4; pp. 386 - 391
• Main Authors: Haris, Mohammad, Nath, Kavindra, Cai, Kejia, Singh, Anup, Crescenzi, Rachelle, Kogan, Feliks, Verma, Gaurav, Reddy, Sanjana, Hariharan, Hari, Melhem, Elias R., Reddy, Ravinder
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2013; Wiley Subscription Services, Inc
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; brain; Brain - metabolism; Brain - pathology; chemical exchange saturation transfer imaging; glutamate; Glutamic Acid - metabolism; Humans; Magnetic Resonance Spectroscopy; Mice, Transgenic; MRI; MRS; Neurotransmitter Agents - metabolism; Reproducibility of Results; brain; MRI; Alzheimer's disease; chemical exchange saturation transfer imaging; glutamate; MRS
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.2875

Glutamate (Glu) is a major excitatory neurotransmitter in the brain and has been shown to decrease in the early stages of Alzheimer's disease (AD). Using a glutamate chemical (amine) exchange saturation transfer (GluCEST) method, we imaged the change in [Glu] in the APP‐PS1 transgenic mouse model of AD at high spatial resolution. Compared with wild‐type controls, AD mice exhibited a notable reduction in GluCEST contrast (~30%) in all areas of the brain. The change in [Glu] was further validated through 1H MRS. A positive correlation was observed between GluCEST contrast and 1H MRS‐measured Glu/total creatine ratio. This method potentially provides a novel noninvasive biomarker for the diagnosis of the disease in preclinical stages and enables the development of disease‐modifying therapies for AD. Copyright © 2012 John Wiley & Sons, Ltd. Glutamate (Glu) concentration changes in the APP‐PS1 transgenic mouse model of Alzheimer's disease (AD) were imaged at high resolution using the glutamate chemical (amine) exchange saturation transfer (GluCEST) method. Compared with wild‐type controls, AD mice exhibited a significant reduction in GluCEST contrast in all areas of the brain, with a maximum decrease in the hippocampus. A positive correlation was observed between GluCEST contrast and 1H MRS‐measured [Glu].