Novel blood-based proteomic signatures across multiple neurodegenerative diseases

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-03-27 DOI:10.1002/alz.70116

Robert Durcan, Amanda Heslegrave, Peter Swann, Julia Goddard, Leonidas Chouliaras, Alexander G. Murley, George Savulich, W. Richard Bevan-Jones, Owen Swann, Nicholas J. Ashton, Kaj Blennow, William McEwan, Henrik Zetterberg, James B. Rowe, John T. O'Brien, Maura Malpetti

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引用次数: 0

Abstract

INTRODUCTION

Blood-based biomarkers have the potential to support early and accurate diagnoses of neurodegenerative diseases, which are sensitive to molecular pathology and are predictive of outcome. We evaluated a novel multiplex proteomic method in people with diverse neurodegenerative diseases.

METHODS

Serum from people with Alzheimer's disease (N = 36), Lewy body dementia (N = 34), frontotemporal dementia (N = 36), and progressive supranuclear palsy (N = 36) and age-matched controls (N = 30) was analyzed with the nucleic acid linked immuno-sandwich assay (NULISA) central nervous system panel (≈ 120 analytes) and inflammation panel (250 analytes). Biomarkers were compared across groups and included as predictors of survival.

RESULTS

The NULISA panels demonstrated high sensitivity and reliability for detecting multiple biomarkers across neurodegenerative disorders. There were condition-specific proteomic biomarkers, while neurofilament light chain, corticotropin-releasing hormone, CD276, and a data-driven inflammation pattern were significant transdiagnostic outcome predictors.

DISCUSSION

The sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.

Highlights

We tested the novel technology nucleic acid linked immuno-sandwich assay (NULISA) in people with diverse neurodegenerative diseases, which demonstrated high sensitivity and reliability for detecting multiple biomarkers in serum samples.
We compared the NULISA central nervous system serum results to single molecule array (Simoa) plasma assays for phosphorylated tau (p-tau)217, p-tau231, neurofilament light chain (NfL), and glial fibrillary acidic protein, finding strong correlations.
Increased levels of serum NfL were identified across all patient groups and most elevated in the frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP) cohorts, while p-tau epitopes were the most significant markers in patients with Alzheimer's disease (AD) and Lewy body dementia.
Patients with FTD and PSP showed upregulation of many inflammation markers, compared to controls and patients with AD.
We found condition-specific proteomic biomarkers, while NfL, corticotropin-releasing hormone, CD276, and data-driven immune signatures were significant transdiagnostic predictors of clinical outcomes (survival rates).

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引言基于血液的生物标记物有可能支持神经退行性疾病的早期准确诊断，这些标记物对分子病理学很敏感，并能预测预后。我们对一种新型多重蛋白质组学方法进行了评估，该方法适用于多种神经退行性疾病患者。方法：用核酸连接免疫三明治测定法（NULISA）分析阿尔茨海默病（36 例）、路易体痴呆（34 例）、额颞叶痴呆（36 例）和进行性核上性麻痹（36 例）患者以及年龄匹配的对照组（30 例）的血清中的中枢神经系统面板（≈ 120 个分析物）和炎症面板（250 个分析物）。对各组的生物标志物进行了比较，并将其作为预测生存率的指标。结果 NULISA面板在检测神经退行性疾病的多种生物标记物方面表现出较高的灵敏度和可靠性。这些生物标记物具有条件特异性，而神经丝蛋白轻链、促肾上腺皮质激素释放激素、CD276 和数据驱动的炎症模式则是重要的跨诊断结果预测因子。讨论灵敏的 NULISA 多路复用方法支持鉴别诊断和目标鉴定，并提供了预后信息丰富的痴呆症相关生物标记物。亮点我们在患有多种神经退行性疾病的人群中测试了核酸连接免疫三明治测定（NULISA）这一新型技术，结果表明它在检测血清样本中的多种生物标记物方面具有很高的灵敏度和可靠性。我们将 NULISA 中枢神经系统血清检测结果与单分子阵列（Simoa）血浆检测磷酸化 tau（p-tau）217、p-tau231、神经丝蛋白轻链（NfL）和胶质纤维酸性蛋白的结果进行了比较，发现两者之间存在很强的相关性。在所有患者组中都发现了血清 NfL 水平的升高，其中额颞叶痴呆（FTD）和进行性核上性麻痹（PSP）患者组群的 NfL 水平升高最为明显，而 p-tau 表位是阿尔茨海默病（AD）和路易体痴呆患者中最重要的标记物。与对照组和AD患者相比，FTD和PSP患者的许多炎症标记物都出现了上调。我们发现了特定病情的蛋白质组生物标志物，而NfL、促肾上腺皮质激素释放激素、CD276和数据驱动的免疫特征则是临床结果（存活率）的重要跨诊断预测因子。

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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.