Reduced glutamate neurotransmission in patients with Alzheimer's disease?an in vivo 13C magnetic resonance spectroscopy study

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Abstract
Cognitive impairment in Alzheimer's disease (AD) is not fully explained. PET indicates reduced cerebral metabolic rate for glucose. Since glutamate neurotransmission (GNT) consumes more than 80% of the ATP generated from metabolism, a pilot study was carried out to determine the neuronal tricarboxylic acid cycle (TCA) based on the hypothesis that reduced GNT could contribute to cognitive impairment in AD. Three AD patients with cognitive impairment (mini-mental state exam: 24 vs 30, P N-acetyl aspartate (NAA)/Creatine (Cr) (PP1H and proton-decoupled 13C MR brain spectra were acquired from combined posterior-parietal white matter and posterior-cingulate gray matter every 5 min for 140 min. 13C magnetic resonance spectroscopy (MRS) measures of glucose oxidation and neuronal TCA rate, including prolonged time to 13C enrichment of glutamate (Glu2) (P3) (P2/Glu4 between 60 and 100 min (P13C measures of GNT, glutamine (Gln)2/Glu2 (P2/glucose: 0.34 vs 0.86, P=ns and Glu4/glucose 0.26 vs 0.83, P=ns), were also reduced. 13C MRS measures of neuronal TCA cycle, glucose oxidation and GNT were significantly correlated with measures of neuronal integrity: NAA/Cr, [NAA] and mI/NAA as determined by 1H MRS (R 2=0.73–0.95; P<0.05–0.01), suggesting that impairment of GNT may be a contributing factor in the cognitive impairment characteristic of AD.