Yoshida Madoka, Uemura Takeshi, Mizoi Mutsumi, Waragai Masaaki, Sakamoto Akihiko, Terui Yusuke, Kashiwagi Keiko, Igarashi Kazuei
Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba, Japan.
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.
J Alzheimers Dis. 2023;92(1):361-369. doi: 10.3233/JAD-220912.
Dementia, including Alzheimer's disease (AD), is one of the serious diseases at advanced age, and its early detection is important for maintaining quality of life (QOL).
In this study, we sought novel biomarkers for dementia in urine.
Samples of urine were collected from 57 control subjects without dementia, 62 mild cognitive impairment (MCI) patients, and 42 AD patients. Mini-Mental State Examination (MMSE) was evaluated when subjects were examined by medical doctors. Urinary amino acid (lysine)-conjugated acrolein (AC-Acro) was measured using N ɛ-(3-formyl-3, 4-dehydropiperidine) lysine (FDP-Lys) ELISA kit, and taurine content was measured using a taurine assay kit. Values were normalized by creatinine content which was measured with the colorimetric assay kit.
We found that urinary amino acid (lysine)-conjugated acrolein (AC-Acro) and taurine negatively correlated with MMSE score and are significantly lower in dementia patients compared to the normal subjects. When AC-Acro and taurine were evaluated together with age using an artificial neural network model, median relative risk values for subjects with AD, subjects with mild cognitive impairment, and control subjects were 0.96, 0.53, and 0.06, respectively.
Since urine is relatively easy to collect, our findings provide a novel biomarker for dementia without invasiveness.
痴呆症,包括阿尔茨海默病(AD),是老年人的严重疾病之一,其早期检测对于维持生活质量(QOL)很重要。
在本研究中,我们寻找尿液中痴呆症的新型生物标志物。
收集了57名无痴呆症的对照受试者、62名轻度认知障碍(MCI)患者和42名AD患者的尿液样本。当受试者接受医生检查时,评估简易精神状态检查表(MMSE)。使用Nɛ-(3-甲酰基-3,4-脱氢哌啶)赖氨酸(FDP-Lys)ELISA试剂盒测量尿氨基酸(赖氨酸)结合丙烯醛(AC-Acro),并使用牛磺酸检测试剂盒测量牛磺酸含量。通过用比色测定试剂盒测量的肌酐含量对数值进行标准化。
我们发现尿氨基酸(赖氨酸)结合丙烯醛(AC-Acro)和牛磺酸与MMSE评分呈负相关,并且与正常受试者相比,痴呆症患者的含量显著降低。当使用人工神经网络模型将AC-Acro和牛磺酸与年龄一起评估时,AD患者、轻度认知障碍患者和对照受试者的中位相对风险值分别为0.96、0.53和0.06。
由于尿液相对容易收集,我们的研究结果提供了一种非侵入性的痴呆症新型生物标志物。