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Journal Article

Gray matter gamma-hydroxy-butyric acid and glutamate reflect beta-amyloid burden at old age


Henning,  A       
Research Group MR Spectroscopy and Ultra-High Field Methodology, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Schreiner, S., Van Bergen, J., Gietl, A., Buck, A., Hock, C., Pruessmann, K., et al. (2024). Gray matter gamma-hydroxy-butyric acid and glutamate reflect beta-amyloid burden at old age. Alzheimer's and Dementia, 16(2): e12587. doi:10.1002/dad2.12587.

Cite as: https://hdl.handle.net/21.11116/0000-000F-3B9D-F
Gamma-hydroxy-butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain ß-amyloid (Aß) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 ± 6 years) received high-resolution atlas-based 1H-magnetic resonance spectroscopic imaging (MRSI) at ultra-high magnetic field strength of 7 Tesla for gray matter-specific assessment of GABA and glutamate. We assessed Aß burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher Aß-burden (ß = 0.60, p < 0.05; ß = 0.64, p < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) (p = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (ß = -0.48; p = 0.02; ß = -0.50; p = 0.01). In vivo measures of GABA and glutamate reflect early AD pathology at old age, in an APOE4-dependent manner. GABA and glutamate may represent promising biomarkers and potential targets for early therapeutic intervention and prevention.