Capillary electrophoresis-mass spectrometry-based metabolome analysis of serum and saliva from neurodegenerative dementia patients
Capillary electrophoresis-mass spectrometry-based metabolome analysis of serum and saliva from neurodegenerative dementia patients
复制标题
DOI：
10.1002/elps.201300019
复制
发表时间：
2013-10-01
期刊：
影响因子：
2.9
通讯作者：
Tomita, Masaru
中科院分区：
文献类型：
--
作者：
Tsuruoka, Mayuko;Hara, Junko;Tomita, Masaru
尽管全球发病率上升，但神经退行性痴呆的确切发病机制和客观诊断术语仍存在争议，对该疾病的全面了解仍然缺乏。在这里，我们对神经退行性痴呆患者(n=10)的血清和唾液进行了代谢组学分析，这些患者包括阿尔茨海默病、额颞叶痴呆和路易体病，以及年龄匹配的健康对照组(n=9)。用CE-TOF-MS检测，痴呆患者血清中的6种代谢物(-丙氨酸、肌酐、羟脯氨酸、谷氨酰胺、异柠檬酸和胞苷)和唾液中的2种代谢物(精氨酸和酪氨酸)与对照组相比有显著差异。通过多变量分析，血清被确认为比唾液更有效的生物诊断液体；此外，总共有45种代谢物被确定为候选标志物，可以区分至少一对诊断组和健康对照组。这些代谢产物可能为痴呆的多时相筛查提供了一种客观的诊断方法。此外，在血清中检测到的几种三羧酸循环化合物存在诊断类型依赖的差异，表明痴呆患者的葡萄糖代谢的一些途径可能发生改变。这项初步研究揭示了不同神经退行性痴呆之间代谢组谱的新变化，这将有助于病因学研究。
Despite increasing global prevalence, the precise pathogenesis and terms for objective diagnosis of neurodegenerative dementias remain controversial, and comprehensive understanding of the disease remains lacking. Here, we conducted metabolomic analysis of serum and saliva obtained from patients with neurodegenerative dementias (n = 10), including Alzheimer's disease, frontotemporal lobe dementia, and Lewy body disease, as well as from age-matched healthy controls (n = 9). Using CE-TOF-MS, six metabolites in serum (-alanine, creatinine, hydroxyproline, glutamine, iso-citrate, and cytidine) and two in saliva (arginine and tyrosine) were significantly different between dementias and controls. Using multivariate analysis, serum was confirmed as a more efficient biological fluid for diagnosis compared to saliva; additionally, 45 metabolites in total were identified as candidate markers that could discriminate at least one pair of diagnostic groups from the healthy control group. These metabolites possibly provide an objective method for diagnosing dementia-type by multiphase screening. Moreover, diagnostic-type-dependent differences were observed in several tricarboxylic acid cycle compounds detected in serum, indicating that some pathways in glucose metabolism may be altered in dementia patients. This pilot study revealed novel alterations in metabolomic profiles between various neurodegenerative dementias, which would contribute to etiological investigations.