Durcan Robert, Heslegrave Amanda, Swann Peter, Goddard Julia, Chouliaras Leonidas, Murley Alexander G, Savulich George, Bevan-Jones W Richard, Swann Owen, Ashton Nicholas J, Blennow Kaj, McEwan William, Zetterberg Henrik, Rowe James B, O'Brien John T, Malpetti Maura
Department of Clinical Neurosciences, University of Cambridge and Cambridge University Hospitals NHS Trust, Cambridge, UK.
UK Dementia Research Institute, University College London, London, UK.
Alzheimers Dement. 2025 Mar;21(3):e70116. doi: 10.1002/alz.70116.
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.
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.
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.
The sensitive NULISA multiplex approach supports differential diagnosis and target identification, with prognostically informative dementia-related biomarkers.
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).
基于血液的生物标志物有潜力辅助神经退行性疾病的早期准确诊断，这些疾病对分子病理学敏感且可预测预后。我们评估了一种针对多种神经退行性疾病患者的新型多重蛋白质组学方法。
采用核酸连接免疫夹心分析法（NULISA）中枢神经系统检测板（约120种分析物）和炎症检测板（250种分析物），对阿尔茨海默病患者（N = 36）、路易体痴呆患者（N = 34）、额颞叶痴呆患者（N = 36）、进行性核上性麻痹患者（N = 36）以及年龄匹配的对照组（N = 30）的血清进行分析。对各疾病组的生物标志物进行比较，并将其作为生存预测指标。
NULISA检测板在检测多种神经退行性疾病的生物标志物方面显示出高灵敏度和可靠性。存在疾病特异性的蛋白质组学生物标志物，而神经丝轻链、促肾上腺皮质激素释放激素、CD276以及一种数据驱动的炎症模式是显著的跨诊断预后预测指标。
灵敏的NULISA多重检测方法有助于鉴别诊断和靶点识别，并提供具有预后信息的痴呆相关生物标志物。
我们在多种神经退行性疾病患者中测试了新技术核酸连接免疫夹心分析法（NULISA），该方法在检测血清样本中的多种生物标志物方面显示出高灵敏度和可靠性。我们将NULISA中枢神经系统血清检测结果与单分子阵列（Simoa）血浆检测的磷酸化tau（p-tau）217、p-tau231、神经丝轻链（NfL）和胶质纤维酸性蛋白结果进行比较，发现相关性很强。在所有患者组中均检测到血清NfL水平升高，在额颞叶痴呆（FTD）和进行性核上性麻痹（PSP）队列中升高最为明显，而p-tau表位是阿尔茨海默病（AD）和路易体痴呆患者中最显著的标志物。与对照组和AD患者相比，FTD和PSP患者的许多炎症标志物上调。我们发现了疾病特异性的蛋白质组学生物标志物，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是临床结局（生存率）的显著跨诊断预测指标。
