Lagging Cecilia, Pedersen Annie, Petzold Max, Furutjäll Sofia, Samuelsson Hans, Jood Katarina, Stanne Tara M, Jern Christina
Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Box 440, 405 30, Gothenburg, Sweden.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Gothenburg, Sweden.
Sci Rep. 2025 May 2;15(1):15328. doi: 10.1038/s41598-025-99735-w.
The biological underpinnings of post-stroke cognitive function are largely unknown, and protein investigations can point towards important pathways for further study. We profiled plasma levels of 91 neurology-related proteins (Olink Neurology panel) and serum Neurofilament light chain (NfL) levels in 205 cases in the Sahlgrenska Academy Study on Ischemic Stroke. Blood was sampled in the acute and convalescent (3 months post-stroke) phase. Cognitive outcome was evaluated by the Barrow Neurological Institute Screen for Higher Cerebral Functions 7 years post-stroke. In linear regression models, 6 and 5 proteins in the acute and convalescent phase, respectively, were univariably associated with cognitive outcome at False Discovery Rate (FDR) < 0.05, and 9 and 8 at p < 0.05 after adjustment for age, sex, education and sampling day (model 1) and/or additional adjustment for stroke severity (model 2). Of these, 15 proteins contributed with information in multi-protein models on at least one time-point. These included brain-expressed proteoglycans (NCAN, BCAN, GPC5, SPOCK1); contactin-5 (CNTN5); metabolic enzymes (HAGH, NMNAT1); cluster of differentiation (CD)-proteins (SIGLEC1, CLEC10A, CD200R1); GDNF family receptor alpha-1 (GFR-alpha-1); brorin (VWC2); beta-nerve growth factor (beta-NGF); myostatin (GDF-8); and NfL. We identified novel candidate protein biomarkers of post-stroke cognitive outcome that likely reflect different biological processes, warranting further exploration.
中风后认知功能的生物学基础在很大程度上尚不明确，而蛋白质研究可为进一步研究指明重要途径。在萨尔格伦斯卡学院缺血性中风研究中，我们分析了205例患者血浆中91种神经学相关蛋白质（Olink神经学检测板）的水平以及血清神经丝轻链（NfL）水平。在急性期和恢复期（中风后3个月）采集血液样本。中风后7年，通过巴罗神经学研究所高级脑功能筛查评估认知结果。在线性回归模型中，急性期和恢复期分别有6种和5种蛋白质在错误发现率（FDR）<0.05时与认知结果单变量相关，在调整年龄、性别、教育程度和采样日（模型1）和/或进一步调整中风严重程度（模型2）后，p<0.05时分别有9种和8种蛋白质与之相关。其中，15种蛋白质在至少一个时间点的多蛋白质模型中提供了信息。这些蛋白质包括脑表达蛋白聚糖（NCAN、BCAN、GPC5、SPOCK1）；接触蛋白5（CNTN5）；代谢酶（HAGH、NMNAT1）；分化簇（CD）蛋白（SIGLEC1、CLEC10A、CD200R1）；胶质细胞源性神经营养因子家族受体α-1（GFR-α-1）；布罗林（VWC2）；β-神经生长因子（β-NGF）；肌肉生长抑制素（GDF-8）；以及NfL。我们确定了中风后认知结果的新型候选蛋白质生物标志物，它们可能反映不同的生物学过程，值得进一步探索。
