From the Department of Neurology (D.C.L., K.L.H., M.D.S., E.S.V., H.M., G.A., O.E., A.L.D., B.E.D., K.C.F., E.S.S., S.S., P.A.C., P.B.), Johns Hopkins University School of Medicine; Laboratory of Clinical Investigation (M.V., J.B., D.K.), National Institute on Aging; and Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD.
Neurol Neuroimmunol Neuroinflamm. 2024 Jul;11(4):e200257. doi: 10.1212/NXI.0000000000200257. Epub 2024 May 16.
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).
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.
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; = 0.04), cortical gray matter (rho = 0.34; = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; = 0.04) and cortical gray matter (rho = 0.31; = 0.049) atrophy.
NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.
评估从富含神经元的细胞外囊泡 (NEV) 中分离出的突触蛋白的变化率是否与多发性硬化症 (MS) 患者的脑和视网膜萎缩有关。
对多发性硬化症患者进行了连续采血、磁共振成像 (MRI) 和光学相干断层扫描 (OCT) 扫描。使用 ELISA 从血浆中免疫捕获 NEV，并测量突触蛋白素和突触小体蛋白的含量。确定和关联了突触蛋白、脑和视网膜萎缩的个体特异性变化率。
共纳入 50 名多发性硬化症患者，其中 46 名患者进行了 MRI 检查，45 名患者进行了 OCT 检查。NEV 突触蛋白素的变化率与全脑 (rho = 0.31; = 0.04)、皮质灰质 (rho = 0.34; = 0.03)、视盘周围视网膜神经纤维层 (rho = 0.37; = 0.01) 和节细胞/内丛状层 (rho = 0.41; = 0.006) 萎缩相关。NEV 突触小体蛋白的变化率也与全脑 (rho = 0.31; = 0.04) 和皮质灰质 (rho = 0.31; = 0.049) 萎缩相关。
源自 NEV 的突触蛋白可能反映神经退行性变，并可能为 MS 疾病进展提供额外的循环生物标志物。
