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

IF 13 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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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.