Saga Women's Junior College, Saga, Japan.
R & D Center, Nipro Co., Kusatsu, Shiga, Japan.
J Alzheimers Dis. 2020;77(2):773-780. doi: 10.3233/JAD-200234.
In the treatment of Alzheimer's disease (AD), it is thought to be most effective to intervene at the earliest and mildest stages. For diagnosis at the earliest and mildest stages, it is desirable to use a biomarker that can be detected by a minimally invasive, cost-effective technique. Recent research indicates the potential clinical usefulness of plasma amyloid-β (Aβ) biomarkers in predicting brain Aβ burden at an individual level. However, it is as yet unproven that accumulation of Aβ necessarily leads to the development of AD.
Homocysteic acid (HCA) is useful as an early diagnostic marker for mild cognitive impairment (MCI), a pre-stage of AD.
We measured the concentration of HCA, tumor necrosis factor alpha, cortisol, tau, and phosphorylated tau (p-tau) in patients' plasma of 22 AD, 23 MCI, and 9 negative control (NC) cases.
Plasma HCA was shown to be very high in areas under the receiver operating characteristic curves (AUC), distinguished between MCI and NC; when 0.116μM was chosen as the analyte concentration cut-off, the sensitivity was 95.7% and the specificity was 70%.
Our results suggest that plasma HCA may be a useful indicator as an early diagnostic marker for MCI. HCA seems to be upstream from neurodegeneration in the AD pathology because it is known that an overactive NMDA receptor promotes amyloid polymerization and tau phosphorylation in AD.
在阿尔茨海默病(AD)的治疗中,人们认为在最早和最轻微的阶段进行干预最为有效。为了在最早和最轻微的阶段进行诊断,理想情况下是使用一种可以通过微创、具有成本效益的技术检测到的生物标志物。最近的研究表明,血浆淀粉样蛋白-β(Aβ)生物标志物在预测个体大脑 Aβ负担方面具有潜在的临床应用价值。然而,Aβ的积累是否必然导致 AD 的发展还有待证实。
同型半胱氨酸(HCA)是轻度认知障碍(MCI)的早期诊断标志物,MCI 是 AD 的前期阶段。
我们测量了 22 例 AD、23 例 MCI 和 9 例阴性对照(NC)患者血浆中 HCA、肿瘤坏死因子-α、皮质醇、tau 和磷酸化 tau(p-tau)的浓度。
血浆 HCA 在受试者工作特征曲线(ROC)下的面积(AUC)非常高,能够区分 MCI 和 NC;当选择 0.116μM 作为分析物浓度的截断值时,灵敏度为 95.7%,特异性为 70%。
我们的结果表明,血浆 HCA 可能是 MCI 的早期诊断标志物的有用指标。HCA 似乎是 AD 病理中神经退行性变的上游标志物,因为众所周知,NMDA 受体过度活跃会促进 AD 中淀粉样蛋白聚合和 tau 磷酸化。