Department of Medical Sciences, Neurology, Uppsala University Hospital, 751 85, Uppsala, Sweden.
Department of Clinical Neurophysiology, Neurosurgery and Neurology, Uppsala University Hospital, 751 85, Uppsala, Sweden.
Mol Brain. 2022 Jun 29;15(1):52. doi: 10.1186/s13041-022-00935-6.
Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.
胶质纤维酸性蛋白（GFAP）、髓鞘碱性蛋白（MBP）、神经丝轻链（NFL）、tau 和泛素羧基末端水解酶 L1（UCHL1）是五种神经胶质蛋白，被用作 CSF 或血液中神经组织损伤的生物标志物。目前对于这些蛋白质在中枢神经系统（CNS）不同解剖区域的浓度差异知之甚少，因为之前的研究集中在基因表达或非定量蛋白质分析上，限制了这些生物标志物的可解释性。本研究旨在绘制这些蛋白质在 CNS 不同区域的组织含量图谱。使用 ELISA 法在 10 名 24 至 50 岁已故供体的 CNS 17 个选定解剖区域的死后组织匀浆中测定了所研究蛋白质的浓度，在适当情况下，根据死后间隔时间对蛋白质浓度进行了调整。总共分析了 168 个组织样本。GFAP、MBP、NFL、tau 和 UCHL1 的浓度在不同的 CNS 区域之间存在很大差异。CNS 中高度髓鞘化区域的 MBP 浓度比大脑皮层高 10 倍，而 tau 则呈现相反的模式。GFAP、NFL 和 tau 在大脑白质中表现出前后梯度。小脑所有研究蛋白的浓度均较低。总之，GFAP、MBP、NFL、tau 和 UCHL1 的组织浓度在整个 CNS 中均已确定。在解释与 CNS 损伤过程的范围和定位相关的这些生物标志物的循环水平时，这些信息可以用作参考。
