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

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 (A ss) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 +/- 6 years) received high-resolution atlas-based H-1-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 A ss burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher A ss-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.