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用于阿尔茨海默病突触功能障碍的脑脊液生物标志物组合

Cerebrospinal fluid biomarker panel for synaptic dysfunction in Alzheimer's disease.

作者信息

Nilsson Johanna, Gobom Johan, Sjödin Simon, Brinkmalm Gunnar, Ashton Nicholas J, Svensson Johan, Johansson Per, Portelius Erik, Zetterberg Henrik, Blennow Kaj, Brinkmalm Ann

机构信息

Institute of Neuroscience and Physiology The Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden.

Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.

出版信息

Alzheimers Dement (Amst). 2021 May 1;13(1):e12179. doi: 10.1002/dad2.12179. eCollection 2021.

DOI:10.1002/dad2.12179
PMID:33969172
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8087978/
Abstract

INTRODUCTION

Synaptic dysfunction and degeneration is one of the earliest events in Alzheimer's disease (AD) and the best correlate of cognitive decline. Thus, identification and validation of biomarkers reflecting synaptic degeneration to be used as prognostic biomarkers are greatly needed.

METHOD

Solid-phase extraction and parallel reaction monitoring mass spectrometry were used to quantify 17 synaptic proteins in CSF, in two cross-sectional studies including AD (n = 52) and controls (n = 37).

RESULTS

Increased concentrations of beta-synuclein, gamma-synuclein, neurogranin, phosphatidylethanolamine-binding protein 1, and 14-3-3 proteins were observed in AD patients compared to controls, while neuronal pentraxin-2 and neuronal pentraxin receptor were decreased.

DISCUSSION

We have established a method with a novel panel of synaptic proteins as biomarkers of synaptic dysfunction. The results indicate that several of the proteins included in the panel may serve as synaptic biomarkers for AD.

摘要

引言

突触功能障碍和退化是阿尔茨海默病(AD)最早出现的事件之一,也是认知能力下降的最佳关联因素。因此,迫切需要识别和验证反映突触退化的生物标志物,以用作预后生物标志物。

方法

在两项横断面研究中,包括AD患者(n = 52)和对照组(n = 37),采用固相萃取和平行反应监测质谱法定量脑脊液中的17种突触蛋白。

结果

与对照组相比,AD患者脑脊液中β-突触核蛋白、γ-突触核蛋白、神经颗粒素、磷脂酰乙醇胺结合蛋白1和14-3-3蛋白的浓度升高,而神经元五聚体蛋白2和神经元五聚体蛋白受体降低。

讨论

我们建立了一种以一组新型突触蛋白作为突触功能障碍生物标志物的方法。结果表明,该组中包含的几种蛋白质可能作为AD的突触生物标志物。

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Pathophysiological subtypes of Alzheimer's disease based on cerebrospinal fluid proteomics.基于脑脊液蛋白质组学的阿尔茨海默病病理生理亚型。
Brain. 2020 Dec 1;143(12):3776-3792. doi: 10.1093/brain/awaa325.
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Fluid Biomarkers for Synaptic Dysfunction and Loss.用于突触功能障碍和丧失的体液生物标志物
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Amyloid beta, tau, synaptic, neurodegeneration, and glial biomarkers in the preclinical stage of the Alzheimer's continuum.阿尔茨海默病连续体临床前期的淀粉样β、tau、突触、神经退行性变和神经胶质生物标志物。
血浆囊泡相关膜蛋白2和胶质纤维酸性蛋白与无痴呆症老年人的突触密度相关。
Brain Commun. 2025 May 27;7(4):fcaf207. doi: 10.1093/braincomms/fcaf207. eCollection 2025.
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Development and validation of a novel Simoa assay for NPTX2 in Alzheimer's disease and Down syndrome.一种用于阿尔茨海默病和唐氏综合征中NPTX2的新型单分子阵列检测方法的开发与验证
Alzheimers Dement. 2025 Jun;21(6):e70241. doi: 10.1002/alz.70241.
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Mol Neurodegener. 2025 May 6;20(1):52. doi: 10.1186/s13024-025-00841-0.
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Synaptic protein CSF levels relate to memory scores in individuals without dementia.突触蛋白脑脊液水平与无痴呆症个体的记忆评分相关。
Alzheimers Res Ther. 2025 Mar 3;17(1):56. doi: 10.1186/s13195-025-01703-z.
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