用于临床前阿尔茨海默病的诊断和预后的血浆生物标志物。

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease.

机构信息

Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

出版信息

Alzheimers Dement. 2022 Jun;18(6):1141-1154. doi: 10.1002/alz.12447. Epub 2021 Sep 8.

DOI:10.1002/alz.12447

PMID:34494715

Abstract

INTRODUCTION

This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD).

METHODS

Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aβ-) or presence (Aβ+) of brain amyloidosis.

RESULTS

Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aβ+ CU compared with Aβ- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aβ+ and Aβ- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aβ+ CU and increased NFL in Aβ- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume.

DISCUSSION

These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

摘要

简介

本研究平行比较了血浆神经胶质纤维酸性蛋白（GFAP）、总 tau（t-tau）、磷酸化 tau（p-tau181 和 p-tau231）和神经丝轻链（NFL）在临床前阿尔茨海默病（AD）中的诊断和纵向监测潜力。

方法

使用 Simoa 测定法在认知正常的老年人（CU）中测量血浆蛋白，这些老年人要么存在（Aβ+）要么不存在（Aβ-）脑淀粉样蛋白。

结果

Aβ+ CU 与 Aβ- CU 相比，血浆 GFAP、t-tau、p-tau181 和 p-tau231 浓度更高。GFAP 在区分 Aβ+和 Aβ- CU 方面具有最大的效应量和曲线下面积（AUC）；然而，GFAP、p-tau181 和 p-tau231 的 AUC 之间没有统计学上的显著差异，但均显著高于 NFL 的 AUC，且 GFAP 的 AUC 高于 t-tau 的 AUC。与包括 AD 风险因素、年龄、性别和载脂蛋白 E 基因（APOE）ε4 状态的基础模型（BM）组合相比，观察到包含 GFAP 的组合具有更高的 AUC（>90%）（BM）与当前研究中调查的任何其他蛋白质的组合。纵向分析显示，在 12 个月的时间内，Aβ+ CU 中 GFAP 和 p-tau181 增加，Aβ- CU 中 NFL 增加。GFAP、p-tau181、p-tau231 和 NFL 与认知显著相关，而与海马体积无显著相关性。