TESTING INOSITOL HYPOTHESIS IN PATIENTS W/ PROBABLE ALZHEIMER DISEASE

该项目的目的是进一步确定 最近发现的脑肌醇（ML）的增加， 提示肌醇代谢紊乱。 肌醇增加 因此，信号可能是一种新鉴定的阿尔茨海默病诊断标记物 可以使用磁共振测量的疾病（AD） 谱 此次合作的目标之一是进一步 确定AD中肌醇代谢缺陷的酶位点 使用4特斯拉的天然丰度13 C MRS直接测定 AD受试者脑中总游离肌醇含量，以排除 甘氨酸对1H NMR中mI诊断峰的贡献 江西篇章 使用1H在1.5特斯拉下获得临床光谱 MRS，其中肌醇基本上是在3.56 ppm处的一个显著峰。 然而，信号变化很小，并且同样可能是由 通过增加甘油、甘氨酸或磷酸肌醇共振， 所有这些都在1.5特斯拉的相同化学位移处共振。 13C MRS可用于区分这些信号，因为甘氨酸共振 例如在不同的化学位移处。 1.5特斯拉时的灵敏度 不允许观察甘氨酸浓度的变化， 通常是1？mol/g。 最近设立的13 C MRS， 特斯拉建议灵敏度应该足以定义 无论是甘氨酸、甘油还是磷酸化肌醇， 在1.5特斯拉下观察到信号变化。 我们已经进行了13 C 对三个从加州飞来的病人的研究。 的 结果明确表明，肌醇升高， 这些病人。

The aim of this project is to further define the significance of the recently discovered increase in cerebral myo-inositol (ml), suggesting that INOSITOL metabolism is disordered. Increased inositol signal may thus be a newly identified diagnostic marker for Alzheimer disease (AD) that can be measured using magnetic resonance spectroscopy. One of the goals of this collaboration is to further define the enzymatic locus of defective inositol metabolism in AD using natural abundance 13C MRS at 4 Tesla to directly assay total-free inositol content of the brain in AD subjects, to exclude contributions from glycine to the diagnostic peak of mI in the 1H MR spectrum. Clinical spectra have been acquired at 1.5 Tesla using 1H MRS, where myo-inositol is essentially one prominent peak at 3.56 ppm. However, the signal change is small and could equally well be caused by increased glycerol, glycine or myo-inositol phosphate resonances, all of which resonate at the same chemical shift at 1.5 Tesla. 13C MRS can be used to distinguish these signals, since glycine resonates for example at a distinct chemical shift. Sensitivity at 1.5 Tesla does not permit observation of changes in the glycine concentration, which is typically 1?mol/g. The recent establishment of 13C MRS at 4 Tesla suggested that the sensitivity should be sufficient to define whether glycine, glycerol or phosphorylated inositol account for the signal change seen at 1.5 Tesla. We have already performed 13C studies on three patients who were flown over from California. The results demonstrated unequivocally that myo-inositol was elevated in these patients.