Lin Alexander P, Shic Frederick, Enriquez Cathleen, Ross Brian D
Clinical Spectroscopy Unit, Huntington Medical Research Institutes, 660 S Fair Oaks Avenue, Pasadena, CA 91105, USA.
MAGMA. 2003 Feb;16(1):29-42. doi: 10.1007/s10334-003-0004-x.
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 (1)H and proton-decoupled (13)C MR brain spectra were acquired from combined posterior-parietal white matter and posterior-cingulate gray matter every 5 min for 140 min.(13)C magnetic resonance spectroscopy (MRS) measures of glucose oxidation and neuronal TCA rate, including prolonged time to (13)C enrichment of glutamate (Glu2) ( 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. (13)C 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=ns and Glu(4)/glucose 0.26 vs 0.83, P=ns), were also reduced.(13)C 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 (1)H 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.
阿尔茨海默病（AD）中的认知障碍尚未得到充分解释。正电子发射断层扫描（PET）显示大脑葡萄糖代谢率降低。由于谷氨酸神经传递（GNT）消耗了代谢产生的80%以上的三磷酸腺苷（ATP），因此进行了一项初步研究，以基于GNT降低可能导致AD认知障碍的假设来确定神经元三羧酸循环（TCA）。三名患有认知障碍的AD患者（简易精神状态检查：24分对30分，P<0.05），N-乙酰天门冬氨酸（NAA）/肌酸（Cr）（P<0.009）和NAA/肌醇（mI）比值均显著降低（P<0.01），以及三名年龄匹配的对照组，每组静脉注射0.014 - 0.016 g/kg/min的99% 1-13C葡萄糖。每5分钟从顶叶后白质和扣带回后灰质联合处采集定量（1）H和质子去耦（13）C磁共振脑谱，共采集140分钟。（13）C磁共振波谱（MRS）对葡萄糖氧化和神经元TCA速率的测量，包括谷氨酸（Glu2）（P<0.004）和碳酸氢盐（HCO₃）（P<0.03）的（13）C富集时间延长，以及60至100分钟之间Glu（2）/Glu（4）的相对富集降低（P<0.04），在AD患者与对照组之间有显著差异。（13）C对GNT、谷氨酰胺（Gln）（2）/Glu（2）（P<0.02）以及谷氨酸富集速率（Glu（2）/葡萄糖：0.34对0.86，P=无显著差异；Glu（4）/葡萄糖0.26对0.83，P=无显著差异）的测量也降低。（13）C MRS对神经元TCA循环、葡萄糖氧化和GNT的测量与神经元完整性的测量显著相关：由（1）H MRS测定的NAA/Cr、[NAA]和mI/NAA（R² = 0.73 - 0.95；P<0.05 - 0.01），表明GNT受损可能是AD特征性认知障碍的一个促成因素。
