Synaptic Protein Loss in Extracellular Vesicles Reflects Brain and Retinal Atrophy in People With Multiple Sclerosis.

IF 7.8 1区医学 Q1 CLINICAL NEUROLOGY

Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-05-16 DOI:10.1212/NXI.0000000000200257

Dimitrios C Ladakis, Michael Vreones, Joseph Blommer, Kimystian L Harrison, Matthew D Smith, Eleni S Vasileiou, Hussein Moussa, Gelareh Ahmadi, Omar Ezzedin, Anna L DuVal, Blake E Dewey, Jerry L Prince, Kathryn C Fitzgerald, Elias S Sotirchos, Shiv Saidha, Peter A Calabresi, Dimitrios Kapogiannis, Pavan Bhargava

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引用次数: 0

Abstract

Objectives: To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS).

Methods: People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs were immunocaptured from plasma, and synaptopodin and synaptophysin proteins were measured using ELISA. Subject-specific rates of change in synaptic proteins, as well as brain and retinal atrophy, were determined and correlated.

Results: A total of 50 people with MS were included, 46 of whom had MRI and 45 had OCT serially. The rate of change in NEV synaptopodin was associated with whole brain (rho = 0.31; p = 0.04), cortical gray matter (rho = 0.34; p = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; p = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; p = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; p = 0.04) and cortical gray matter (rho = 0.31; p = 0.049) atrophy.

Discussion: NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.

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细胞外囊泡中突触蛋白的丢失反映了多发性硬化症患者大脑和视网膜的萎缩。

研究目的评估从神经元富集细胞外囊泡（NEVs）中分离出的突触蛋白的变化率是否与多发性硬化症（MS）患者的脑萎缩和视网膜萎缩有关：方法：对多发性硬化症患者进行连续抽血、核磁共振成像（MRI）和光学相干断层扫描（OCT）随访。从血浆中免疫捕获NEV，并使用ELISA法测定突触蛋白和突触素蛋白。确定了突触蛋白以及脑萎缩和视网膜萎缩的特定受试者变化率，并进行了相关分析：结果：共纳入了 50 名多发性硬化症患者，其中 46 人进行了 MRI 检查，45 人进行了 OCT 序列检查。NEV突触素的变化率与全脑（rho = 0.31; p = 0.04）、皮质灰质（rho = 0.34; p = 0.03）、视网膜周围神经纤维层（rho = 0.37; p = 0.01）和神经节细胞/内层（rho = 0.41; p = 0.006）萎缩相关。NEV突触素的变化率还与全脑（rho = 0.31；p = 0.04）和皮层灰质（rho = 0.31；p = 0.049）萎缩相关：讨论：NEV衍生的突触蛋白可能反映了神经退行性变，并可能为多发性硬化症的疾病进展提供额外的循环生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurology® Neuroimmunology & Neuroinflammation Neuroscience-Neurology

CiteScore

15.60

自引率

2.30%

发文量

219

审稿时长

8 weeks

期刊介绍： Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.