Evaluation of two plasma-based proteotyping assays against APOE ε4 genotyping in a memory clinic setting: The Gothenburg H70 Clinical Studies

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-23 DOI:10.1002/alz.14610

Anna Dittrich, Kaj Blennow, Kübra Tan, Andrea L. Benedet, Ingmar Skoog, Kina Höglund, Nicholas J. Ashton, Henrik Zetterberg, Silke Kern

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Abstract

INTRODUCTION

Apolipoprotein E (APOE) ε4 allele status is associated with an increased risk of Alzheimer's disease and should be determined prior to initiation of anti-amyloid beta antibody treatment, because of increased risk of treatment-related side effects. Plasma-based apoE4 proteotyping may be an alternative to genotyping, with limited clinical evidence.

METHODS

apoE4 proteotyping was performed on 164 memory-clinic patients, using one chemiluminescent enzyme immunoassay (CLEIA) and one nucleic acid–linked immunosandwich assay (NULISA). The assays were evaluated against APOE ε4 blood genotyping.

RESULTS

The CLEIA had a 100% sensitivity and 98.5% specificity to classify APOE ε4 homozygosity and carriership in relation to genotyping. The NULISA had a 92.9% sensitivity and 97.1% specificity to classify homozygosity and a 100% sensitivity and 98.5% specificity to classify carriership.

DISCUSSION

The high performance suggests that the assays may be used as an easily available tool for identifying individuals for definitive APOE ε4 genotyping in a two-step approach.

Highlights

Plasma-based proteotyping presented good to excellent sensitivity in identifying apolipoprotein E (APOE) ε4 homozygosity.
The negative predictive value was also very good to excellent, allowing us to rule out APOE ε4 homozygosity with high precision.
Assays with excellent precision show potential for identifying individuals for definitive APOE ε4 genotyping in a two-step approach.

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两种基于血浆的APOE ε4基因分型方法在记忆临床环境中的评价：哥德堡H70临床研究

载脂蛋白E (APOE) ε4等位基因状态与阿尔茨海默病的风险增加有关，应在开始抗淀粉样蛋白抗体治疗之前确定，因为治疗相关副作用的风险增加。基于血浆的apoE4蛋白分型可能是基因分型的一种替代方法，但临床证据有限。方法采用化学发光酶免疫法（CLEIA）和核酸连锁免疫夹心法（NULISA）对164例记忆临床患者进行apoE4蛋白分型。检测结果与APOE ε4血基因分型比较。结果CLEIA对APOE ε4纯合性和携带者与基因分型的关系的敏感性为100%，特异性为98.5%。该方法对纯合性分类的敏感性为92.9%，特异性为97.1%；对携带性分类的敏感性为100%，特异性为98.5%。高性能表明，该检测方法可以作为一种容易获得的工具，通过两步法确定APOE ε4基因分型。血浆蛋白分型在确定载脂蛋白E (APOE) ε4纯合性方面具有良好至极好的敏感性。阴性预测值也从极好到极好，使我们能够高精度地排除APOE ε4纯合性。精密度极高的检测方法显示了用两步法确定APOE ε4基因分型个体的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.