阿尔茨海默病(AD)是一种进行性疾病,随着人口老龄化,AD患者的数量每年都在增加。AD的病理生理机制之一被认为是代谢组学异常的影响。已经有一些关于AD代谢组学异常的研究,新的生物标志物正在研究中。代谢组学研究一直备受关注,这项研究的目的是确定与AD和轻度认知障碍(MCI)相关的代谢组学生物标志物。在Iyo市进行的中山研究的927名参与者中,爱媛县,本研究选择106例作为对照(n=40),MCI(n=26),和AD(n=40)组,年龄和性别相匹配。对三组进行了代谢组学比较。然后,研究了代谢物与临床症状之间的相关性。还测量了鸟氨酸代谢酶的血液mRNA水平。血浆代谢物中,发现鸟氨酸存在显著差异,尿嘧啶,还有赖氨酸.与对照组和MCI组相比,AD组的鸟氨酸显着降低(对照组与AD:97.2vs.77.4;P=0.01,MCIvs.AD:92.5vs.77.4;P=0.02)。与对照组相比,AD组的尿嘧啶和赖氨酸也显着降低(尿嘧啶,控制vs.AD:272vs.235;P=0.04,赖氨酸,控制vs.AD:208vs.176;P=0.03)。在总样本中,MMSE评分与赖氨酸显著相关,鸟氨酸,胸腺嘧啶,还有尿嘧啶.Barthel指数得分与赖氨酸显著相关。仪器日常生活活动能力(IADL)评分与赖氨酸显著相关,甜菜碱,肌酸,还有胸腺嘧啶.在鸟氨酸代谢途径中,精胺合成酶mRNA水平在AD中显著降低。鸟氨酸减少,与对照组和MCI组相比,AD组与其代谢相关的mRNA表达发生变化,提示鸟氨酸代谢异常与AD之间存在关联。增加的甜菜碱和减少的甲硫氨酸也可能具有作为老年人中较高IADL的标志物的潜力。血浆代谢物可用于预测AD的进展。
Alzheimer\'s disease (AD) is a progressive disease, and the number of AD patients is increasing every year as the population ages. One of the pathophysiological mechanisms of AD is thought to be the effect of metabolomic abnormalities. There have been several studies of metabolomic abnormalities of AD, and new biomarkers are being investigated. Metabolomic studies have been attracting attention, and the aim of this
study was to identify metabolomic biomarkers associated with AD and mild cognitive impairment (MCI). Of the 927 participants in the Nakayama
Study conducted in Iyo City, Ehime Prefecture, 106 were selected for this
study as Control (n = 40), MCI (n = 26), and AD (n = 40) groups, matched by age and sex. Metabolomic comparisons were made across the three groups. Then, correlations between metabolites and clinical symptoms were examined. The blood mRNA levels of the
ornithine metabolic enzymes were also measured. Of the plasma metabolites, significant differences were found in
ornithine, uracil, and lysine. Ornithine was significantly decreased in the AD group compared to the Control and MCI groups (Control vs. AD: 97.2 vs. 77.4; P = 0.01, MCI vs. AD: 92.5 vs. 77.4; P = 0.02). Uracil and lysine were also significantly decreased in the AD group compared to the Control group (uracil, Control vs. AD: 272 vs. 235; P = 0.04, lysine, Control vs. AD: 208 vs. 176; P = 0.03). In the total sample, the MMSE score was significantly correlated with lysine, ornithine, thymine, and uracil. The Barthel index score was significantly correlated with lysine. The instrumental activities of daily living (IADL) score were significantly correlated with lysine, betaine, creatine, and thymine. In the ornithine metabolism pathway, the spermine synthase mRNA level was significantly decreased in AD. Ornithine was decreased, and mRNA expressions related to its metabolism were changed in the AD group compared to the Control and MCI groups, suggesting an association between abnormal ornithine metabolism and AD. Increased betaine and decreased methionine may also have the potential to serve as markers of higher IADL in elderly persons. Plasma metabolites may be useful for predicting the progression of AD.