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

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• 作者：Alexander P. Lin ^A1 ; Frederick Shic ^A2 ; Cathleen Enriquez ^A2 ; Brian D. Ross ^A1
• 关键词：Alzheimer's disease ; Glutamate-glutamine cycle ; ¹³C Magnetic resonance spectroscopy ; ¹³C Glucose infusion ; Glutamate neurotransmission ; N-acetyl aspartate ; Mini-mental state exam
• 刊名：MAGMA Magnetic Resonance Materials in Physics, Biology and Medicine
• 出版年：2003
• 出版时间：February 2003
• 年：2003
• 卷：16
• 期：1
• 页码：29-42
• 全文大小：597 KB

文摘

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<0.05) and significant reduction in both N-acetyl aspartate (NAA)/Creatine (Cr) ( P<0.009) and NAA/myo-inositol (mI) ratio ( P<0.01), and three age-matched controls each received 0.014–0.016 g/kg/min 99%1–13C glucose IV. Quantitative ¹H 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 (Glu ₂) ( P<0.004) and bicarbonate (HCO ₃) ( P<0.03) as well as reduced relative enrichment of Glu ₂/Glu ₄ between 60 and 100 min ( P<0.04), were significantly different in AD patients vs. controls. ¹³C measures of GNT, glutamine (Gln) ₂/Glu ₂ (P<0.02) and rates of glutamate enrichment (Glu ₂/glucose: 0.34 vs 0.86, P