title: Posterior cingulate γ-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype.
abstract: The biomarker potential of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate + glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound B-positive subjects and APOE ε4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid β deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer's disease.
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Riese
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Anton
authors.initials: A
authors.lastname: Gietl
authors.affiliation: Institute of Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland.
authors.forename: Niklaus
authors.initials: N
authors.lastname: Zölch
authors.affiliation: Institute of Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland; Max-Planck Institute for Biological Cybernetics, Tübingen, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Henning
authors.affiliation: Center of MR-Research, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Gorman
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Kälin
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Leh
authors.affiliation: Institute of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Institute of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Warnock
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Center for Functional Brain Imaging, Kenneddy Krieger Institute, Baltimore, MD, USA.
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Institute of Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Luechinger
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.affiliation: Clinic of Neuroradiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Spyros
authors.initials: S
authors.lastname: Kollias
authors.affiliation: Clinic of Neuroradiology, University Hospital Zurich, Zurich, Switzerland. Electronic address: lars.michels@usz.ch.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: APOE; Alzheimer; Beta-amyloid; Dementia; GABA; Glutamate; Glx; MRS; Magnetic resonance spectroscopy; Mild cognitive impairment; PiB; Posterior cingulate cortex