使用核酸连接免疫夹心测定法在阿尔茨海默病和神经退行性疾病中发现生物标志物。

Biomarker discovery in Alzheimer's and neurodegenerative diseases using Nucleic Acid Linked Immuno-Sandwich Assay.

作者信息

Ashton Nicholas J, Benedet Andrea L, Molfetta Guglielmo Di, Pola Ilaria, Anastasi Federica, Fernández-Lebrero Aida, Puig-Pijoan Albert, Keshavan Ashvini, Schott Jonathan, Tan Kubra, Simrén Joel, Gomes Bárbara Fernandes, Montoliu-Gaya Laia, Isaacson Richard, Bongianni Matilde, Tolassi Chiara, Cantoni Valentina, Alberici Antonella, Padovani Alessandro, Zanusso Gianluigi, Pilotto Andrea, Borroni Barbara, Suárez-Calvet Marc, Blennow Kaj, Zetterberg Henrik

机构信息

Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Banner Alzheimer's Institute and University of Arizona, Phoenix, Arizona, USA.

出版信息

Alzheimers Dement. 2025 May;21(5):e14621. doi: 10.1002/alz.14621.

DOI:10.1002/alz.14621

PMID:40401628

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12096316/

Abstract

INTRODUCTION

Recent advancements in immunological methods accurately quantify biofluid biomarkers for Alzheimer's disease (AD) pathology. Despite progress, more biomarkers, ideally in blood, are needed for effective disease monitoring for AD and other neurodegenerative proteinopathies.

METHODS

We used the Nucleic Acid Linked Immuno-Sandwich Assay (NULISA) central nervous system panel for biomarker quantification in plasma, serum, and cerebrospinal fluid of patients with AD, mild cognitive impairment, Lewy body dementia, progranulin (GRN) mutation carriers.

RESULTS

NULISA identified phosphorylated tau217 and neurofilament light chain as the most deregulated biomarkers in the AD continuum and GRN mutation carriers, respectively. Importantly, numerous novel proteomic changes were observed in each disease endophenotype, which included synaptic processing, inflammation, microglial reactivity, TAR DNA-binding protein 43, and α-synuclein pathology.

DISCUSSION

We underline the potential of next-generation biomarker identification tools to detect novel proteomic features that also incorporate established biomarkers. These findings highlight the importance of continued biomarker discovery to improve treatment decisions and help us better understand the complexities of neurodegenerative disorders.

HIGHLIGHTS

The, direct, or indirect, measures in blood that complement phosphorylated tau (p-tau)217 for other proteinopathies or disease progression are urgently needed. Significant novel proteomic changes were observed in each disease endophenotype in plasma, serum, and cerebrospinal fluid, which included proteins involved in synaptic processing, inflammation, microglial reactivity, TAR DNA-binding protein 43, and α-synuclein pathology. Nucleic Acid Linked Immuno-Sandwich Assay continued to unbiasely highlight p-tau217 and neurofilament light chain as the most significantly deregulated blood biomarkers in the Alzheimer's disease continuum and progranulin mutation carriers, respectively.

摘要

引言

免疫方法的最新进展能够准确量化用于阿尔茨海默病（AD）病理学研究的生物流体生物标志物。尽管取得了进展，但为了有效监测AD和其他神经退行性蛋白质病，仍需要更多的生物标志物，理想情况下是血液中的生物标志物。

方法

我们使用核酸连接免疫夹心测定法（NULISA）中枢神经系统检测板对AD、轻度认知障碍、路易体痴呆、原颗粒蛋白（GRN）突变携带者的血浆、血清和脑脊液中的生物标志物进行定量分析。

结果

NULISA分别将磷酸化tau217和神经丝轻链鉴定为AD连续体和GRN突变携带者中失调最严重的生物标志物。重要的是，在每种疾病内表型中都观察到了许多新的蛋白质组学变化，包括突触加工、炎症、小胶质细胞反应性、TAR DNA结合蛋白43和α-突触核蛋白病理学。

讨论

我们强调了下一代生物标志物识别工具检测新蛋白质组学特征（其中也纳入了已确立的生物标志物）的潜力。这些发现凸显了持续进行生物标志物发现对于改善治疗决策的重要性，并有助于我们更好地理解神经退行性疾病的复杂性。

要点

迫切需要在血液中采取直接或间接措施来补充磷酸化tau（p-tau）217，以用于其他蛋白质病或疾病进展的研究。在血浆、血清和脑脊液的每种疾病内表型中都观察到了显著的新蛋白质组学变化，其中包括参与突触加工、炎症、小胶质细胞反应性、TAR DNA结合蛋白43和α-突触核蛋白病理学的蛋白质。核酸连接免疫夹心测定法继续无偏倚地将p-tau217和神经丝轻链分别鉴定为AD连续体和原颗粒蛋白突变携带者中失调最显著的血液生物标志物。