title: Imaging of glutamate neurotransmitter alterations in Alzheimer's disease.
abstract: 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 (1) H MRS. A positive correlation was observed between GluCEST contrast and (1) H 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.
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haris
authors.forename: Kavindra
authors.initials: K
authors.lastname: Nath
authors.forename: Kejia
authors.initials: K
authors.lastname: Cai
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.forename: Rachelle
authors.initials: R
authors.lastname: Crescenzi
authors.forename: Feliks
authors.initials: F
authors.lastname: Kogan
authors.forename: Gaurav
authors.initials: G
authors.lastname: Verma
authors.forename: Sanjana
authors.initials: S
authors.lastname: Reddy
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.forename: Elias R
authors.initials: ER
authors.lastname: Melhem
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid