AD血液早期诊断标志物的研究进展

Blood Biomarkers for Early Diagnosis of Alzheimer’s Disease

阿尔兹海默症(AD)是一种具有漫长病理进程的神经退行性疾病,其发展过程从无症状状态到轻度认知障碍(MCI),最终进展至痴呆可能持续数十年。当前,AD面临的主要挑战是实现早期诊断。目前,用于AD诊断的传统方法主要包括神经心理学量表测试、成像技术(如MRI和PET)以及脑脊液(CSF)标志物检测。然而,量表和成像技术只能用于确诊AD晚期患者,而CSF标志物检测虽然可用于早期AD诊断,但其采集需要进行有创性的腰椎穿刺,因此早期患者的接受程度较低。因此,迫切需要发展非侵入性且便捷的早期AD检测方法,以实现对AD患者的提前预防和治疗。血液标志物检测具备满足早期AD诊断需求的潜力,近年来关于AD早期诊断生物标志物的研究取得了巨大的进展。在本综述中,我们概述了AD血液生物标志物,包括Aβ42/40、p-tau 181、ptau 217、p-tau 231、p-tau 235、GFAP和NFL的研究进展,并从结构生物学的角度讨论了这些标志物目前的局限性。

Alzheimer's disease(AD)is a neurodegenerative disorder characterized by a lengthy pathological progression,starting from an asymptomatic stage and advancing to mild cognitive impairment(MCI),ultimately leading to dementia that can persist for many years.The main challenge in AD presently lies in achieving early diagnosis.Conventional diagnostic methods for AD encompass neuropsychological assessments,imaging technologies such as MRI and PET,and the analysis of cerebrospinal fluid(CSF)biomarkers.However,cognitive tests and imaging techniques can solely confirm AD in its later stages,whereas CSF biomarker analysis,although useful for early AD detection,necessitates an invasive lumbar puncture procedure,resulting in low acceptance among individuals in the early stages of the disease.Consequently,there is an urgent requirement to develop non-invasive and convenient methods for early AD detection,enabling early prevention and treatment for AD patients.Blood-based biomarker analysis holds potential in meeting the demands for early AD diagnosis,and significant progress has been made in recent years in identifying biomarkers for early AD detection.This review provides an overview of blood-based biomarkers for AD,including Aβ42/40,p-tau 181,p-tau 217,p-tau 231,p-tau 235,GFAP,and NFL,while also discussing their current limitations from a structural biology standpoint.