阿尔茨海默病血液的生物标志物研究与展望

Research and Prospect of Blood Biomarkers for Alzheimer’s Disease

阿尔茨海默病(Alzheimer’s disease, AD)是一种不可逆的神经退行性疾病,影响多种高级认知皮质功能,包括记忆、思维能力、定向力、理解、学习能力、语言和判断能力等。近年来AD的诊断和治疗仍存在许多挑战,对于临床前AD或轻度认知障碍(mild cognition impairment, MCI)的AD患者,药物治疗的效果并不显著,目前也没有很好的解决方案。AD最具特征性的生物体液标志物是脑脊液(cerebrospinal fluid, CSF),由于血液比脑脊液更容易获得,因此在临床诊断或筛查以及临床试验中重复取样时,血液取样比脑脊液取样更可取,AD的生物标志物的开发正在从CSF转移到血液中。血液中AD核心发病机制的要素,包括Aβ42沉积、tau蛋白、血浆(plasma)蛋白或脂质(lipids)已显示出它们在AD诊断中的作用和能力,用于AD诊断和预测的血液标记物也得到了广泛的研究。研究证明,MCI和AD患者的血浆Aβ42/40比值显著降低;血浆p-tau231与血浆p-tau181,在AD的失智阶段具有较高的诊断准确性,能将Aβ阳性的AD和MCI病例与Aβ阴性的AD病例较准确地区分。因此,为了在健康人群中筛查AD的风险,血液生物标记物在AD早期诊断和治疗的新靶点,也许是今后AD研究的方向。

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease that affects a variety of high-level cognitive cortical functions, including memory, thinking ability, orientation, understanding, learning ability, language and judgment. In recent years, there are still many challenges in the diagnosis and treatment of AD. For AD patients with preclinical AD or mild cognition impairment (MCI), the effect of drug therapy is not significant, and there is no good solution at present. The most characteristic biofluid marker for AD is cerebrospinal fluid (CSF). Since blood is more readily available than CSF, blood sampling is preferable to CSF sampling for clinical diagnosis or screening and for repeated sampling in clinical trials. Development of biomarkers for AD is moving from CSF to blood. The core pathogenesis of AD in the blood, including Aβ42 deposition, tau protein, plasma proteins or lipids, has shown their role and ability in the diagnosis of AD. Blood markers for the diagnosis and prediction of AD have also been extensively studied. The ratio of plasma Aβ42/40 in patients with MCI and AD was significantly decreased. Plasma p-tau231 and plasma p-tau181 have high diagnostic accuracy in the dementia stage of Alzheimer’s disease, and can distinguish Aβ-positive AD and MCI cases from Aβ-negative AD cases with high accuracy. Therefore, in order to screen the risk of AD in healthy people, blood biomarkers in the early diagnosis and treatment of AD may be the direction of future AD research.