Mullins Roger, Reiter David, Kapogiannis Dimitrios
Laboratory of Neurosciences Intramural Research Program National Institute on Aging/National Institutes of Health (NIA/NIH) Baltimore Maryland.
Laboratory of Clinical Investigation National Institute on Aging Intramural Research Program (NIA-IRP) Baltimore Maryland.
Ann Clin Transl Neurol. 2018 Jan 29;5(3):262-272. doi: 10.1002/acn3.530. eCollection 2018 Mar.
Brain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case-control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD-related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites.
J-modulated Point-Resolved Spectroscopy (J-PRESS) and Prior-Knowledge Fitting (ProFit) software was used to measure glucose and other metabolites in the posterior cingulate/precuneus of 25 AD, 27 older controls, and 27 younger control participants. Clinical assessments for AD participants included cognitive performance measures, insulin resistance metrics and CSF biomarkers.
AD participants showed substantially elevated glucose, lactate, and ascorbate levels compared to older (and younger) controls. In addition, the precuneal glucose elevation discriminated well between AD participants and older controls. Myo-inositol correlated with CSF p-Tau, total Tau, and the Clinical Dementia Rating (CDR) sum-of-boxes score within the AD group.
Higher glucose to creatine ratios in the AD brain likely reflect lower glucose utilization. Our findings reveal pronounced metabolic abnormalities in the AD brain and strongly suggest that brain glucose merits further investigation as a candidate AD biomarker.
脑葡萄糖代谢减低是阿尔茨海默病(AD)的一个显著特征,在这项病例对照研究中,我们使用磁共振波谱(MRS)来评估扣带回后部/楔前叶葡萄糖、乳酸及其他代谢物与AD相关的差异。
使用J调制点分辨波谱(J-PRESS)和先验知识拟合(ProFit)软件测量25名AD患者、27名老年对照者和27名年轻对照者扣带回后部/楔前叶的葡萄糖及其他代谢物。对AD患者的临床评估包括认知功能测量、胰岛素抵抗指标和脑脊液生物标志物。
与老年(及年轻)对照者相比,AD患者的葡萄糖、乳酸和抗坏血酸水平显著升高。此外,楔前叶葡萄糖升高在AD患者和老年对照者之间有很好的区分度。在AD组中,肌醇与脑脊液磷酸化tau蛋白、总tau蛋白及临床痴呆评定量表(CDR)方框总和评分相关。
AD脑内较高的葡萄糖与肌酸比值可能反映了较低的葡萄糖利用率。我们的研究结果揭示了AD脑内明显的代谢异常,并强烈表明脑葡萄糖作为AD生物标志物的候选值得进一步研究。