Dept. of Neurosurgery, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Nat Commun. 2023 Apr 12;14(1):2084. doi: 10.1038/s41467-023-37685-5.
Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-β (Aβ40 and Aβ42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.
通过脑脊液 (CSF) 到血液清除神经毒性脑蛋白最近被认为是至关重要的，并且新引入了血浆神经退行性变生物标志物来预测神经疾病。本研究在 106 名患有神经障碍的个体中，研究了血浆生物标志物 [40 和 42 个氨基酸长的淀粉样蛋白-β (Aβ40 和 Aβ42)、总tau、神经胶质纤维酸性蛋白 (GFAP) 和神经丝轻链 (NfL)] 与通过血管外途径从脑到 CSF 的清除的磁共振成像测量值之间的关联（血脑屏障功能的替代物）和从药代动力学模型的 CSF 到血液清除变量（脑膜淋巴管流出的替代物）。我们还检查了生物标志物如何在白天变化，并与主观睡眠质量相关。神经退行性变生物标志物的血浆浓度与个体和疾病特异性的神经胶质和脑膜淋巴管功能的指数相关，在白天变化，但不受睡眠质量影响。结果表明，神经退行性变生物标志物的血浆浓度与神经胶质和脑膜淋巴管功能的测量值相关。
