阿尔茨海默病相关血浆蛋白的复制研究。

Replication study of plasma proteins relating to Alzheimer's pathology.

机构信息

Department of Psychiatry, University of Oxford, Oxford, UK.

Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK.

出版信息

Alzheimers Dement. 2021 Sep;17(9):1452-1464. doi: 10.1002/alz.12322. Epub 2021 Mar 31.

DOI:10.1002/alz.12322

PMID:33792144

Abstract

INTRODUCTION

This study sought to discover and replicate plasma proteomic biomarkers relating to Alzheimer's disease (AD) including both the "ATN" (amyloid/tau/neurodegeneration) diagnostic framework and clinical diagnosis.

METHODS

Plasma proteins from 972 subjects (372 controls, 409 mild cognitive impairment [MCI], and 191 AD) were measured using both SOMAscan and targeted assays, including 4001 and 25 proteins, respectively.

RESULTS

Protein co-expression network analysis of SOMAscan data revealed the relation between proteins and "N" varied across different neurodegeneration markers, indicating that the ATN variants are not interchangeable. Using hub proteins, age, and apolipoprotein E ε4 genotype discriminated AD from controls with an area under the curve (AUC) of 0.81 and MCI convertors from non-convertors with an AUC of 0.74. Targeted assays replicated the relation of four proteins with the ATN framework and clinical diagnosis.

DISCUSSION

Our study suggests that blood proteins can predict the presence of AD pathology as measured in the ATN framework as well as clinical diagnosis.

摘要

简介

本研究旨在发现和复制与阿尔茨海默病（AD）相关的血浆蛋白质组生物标志物，包括“ATN”（淀粉样蛋白/tau/神经退行性变）诊断框架和临床诊断。

方法

使用 SOMAscan 和靶向检测方法分别测量了 972 名受试者（372 名对照、409 名轻度认知障碍[MCI]和 191 名 AD）的血浆蛋白，分别测量了 4001 种和 25 种蛋白质。

结果

SOMAscan 数据的蛋白质共表达网络分析表明，蛋白质与“N”之间的关系因不同的神经退行性变标志物而有所不同，这表明 ATN 变体不能互换。使用枢纽蛋白、年龄和载脂蛋白 E ε4 基因型，曲线下面积（AUC）为 0.81，区分 AD 与对照，AUC 为 0.74，区分 MCI 转化者与非转化者。靶向检测方法复制了四种蛋白质与 ATN 框架和临床诊断的关系。