Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan; Faculty of Environment and Information Studies, Keio University, Fujisawa, Kanagawa, Japan.
Electrophoresis. 2013 Oct;34(19):2865-72. doi: 10.1002/elps.201300019. Epub 2013 Sep 6.
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 (β-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.
尽管全球患病率不断上升，但神经退行性痴呆的精确发病机制和客观诊断标准仍存在争议，人们对该病的全面认识仍十分有限。在此，我们对包括阿尔茨海默病、额颞叶痴呆和路易体病在内的神经退行性痴呆患者（n = 10）以及年龄匹配的健康对照组（n = 9）的血清和唾液进行了代谢组学分析。使用 CE-TOF-MS，我们在血清中鉴定出了 6 种代谢物（β-丙氨酸、肌酸、羟脯氨酸、谷氨酰胺、异柠檬酸和胞苷）和 2 种唾液代谢物（精氨酸和酪氨酸）在痴呆症患者和对照组之间存在显著差异。使用多变量分析，我们发现与唾液相比，血清是一种更有效的诊断生物流体；此外，还总共鉴定出 45 种代谢物作为候选标志物，可将至少一对诊断组与健康对照组区分开来。这些代谢物可能为通过多相筛选诊断痴呆症提供了一种客观方法。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性差异，表明痴呆患者的某些糖代谢途径可能发生改变。这项初步研究揭示了不同神经退行性痴呆之间代谢组学图谱的新变化，有助于病因学研究。
