采用 6 种联合脑脊液候选物（Aβ、总tau、磷酸化tau、NFL、神经颗粒蛋白和 YKL-40）的阿尔茨海默病生物标志物指导诊断工作流程。

Alzheimer's disease biomarker-guided diagnostic workflow using the added value of six combined cerebrospinal fluid candidates: Aβ, total-tau, phosphorylated-tau, NFL, neurogranin, and YKL-40.

机构信息

AXA Research Fund & Sorbonne Université Chair, Paris, France; Sorbonne Université, AP-HP, GRC n° 21, Alzheimer Precision Medicine (APM), Hôpital de la Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle Épinière (ICM), INSERM U 1127, CNRS UMR 7225, Paris, France; Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France.

Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Rome, Italy; Department of Radiology, "Athinoula A. Martinos" Center for Biomedical Imaging, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

出版信息

Alzheimers Dement. 2018 Apr;14(4):492-501. doi: 10.1016/j.jalz.2017.11.015. Epub 2018 Jan 9.

DOI:10.1016/j.jalz.2017.11.015

PMID:29328927

Abstract

INTRODUCTION

The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation.

METHODS

The combinations ranking in the top 10 according to diagnostic accuracy in differentiating between distinct diagnostic categories were identified.

RESULTS

The single biomarkers or biomarker combinations generating the best area under the receiver operating characteristics (AUROCs) were the following: the combination [amyloid β peptide + phosphorylated tau + neurofilament light chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for distinguishing between ADD and FTD patients (AUROC = 0.82), and t-tau for distinguishing between FTD patients and HC (AUROC = 0.78).

CONCLUSIONS

Novel and established cerebrospinal fluid markers perform with at least fair accuracy in the discrimination between ADD and FTD. The classification of mild cognitive impairment individuals was poor.

摘要

简介

在轻度认知障碍（MCI；n=41）、阿尔茨海默病痴呆（ADD；n=35）、额颞叶痴呆（FTD；n=9）和认知健康对照者（HC；n=21）中，使用 10 倍交叉验证比较了三种核心（淀粉样β肽[i.e., Aβ]、总tau [t-tau]和磷酸化 tau）和三种新型（神经丝轻链蛋白、神经颗粒蛋白和 YKL-40）神经退行性变脑脊液生物标志物的所有组合的诊断和分类性能。

方法

根据区分不同诊断类别的诊断准确性，确定排名前 10 的组合。

结果

产生最佳受试者工作特征曲线（AUROCs）的单个生物标志物或生物标志物组合如下：用于区分 ADD 患者和 HC 的[淀粉样β肽+磷酸化 tau+神经丝轻链]组合（AUROC=0.86），用于区分 ADD 和 FTD 患者的 t-tau（AUROC=0.82），以及用于区分 FTD 患者和 HC 的 t-tau（AUROC=0.78）。