Basic Neurosciences, Genetics and Immunology -original Article A-synuclein in Human Cerebrospinal Fluid Is Principally Derived from Neurons of the Central Nervous System
Basic Neurosciences, Genetics and Immunology -original Article A-synuclein in Human Cerebrospinal Fluid Is Principally Derived from Neurons of the Central Nervous System
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基础神经科学、遗传学和免疫学 - 原创文章人脑脊液中的 A-突触核蛋白主要来源于中枢神经系统的神经元
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通讯作者：
M. Schlossmacher
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作者：
B. Mollenhauer;E. Trautmann;bullet Birgit;Otte bullet;Juliana Ng;A. Spreer;P. Lange;F. Sixel;bullet Mansoureh;Hakimi bullet;J. Vonsattel;bullet Robert;Nussbaum bullet;C. Trenkwalder;M. Schlossmacher
人脑脊液（CSF）中帕金森病相关的α-突触核蛋白（aSyn）的来源仍然未知。我们决定测量人CSF标本中aSyn的浓度及其梯度，并将其与血清进行比较，以探索其来源。我们将CSF与血清中的aSyn浓度（Q aSyn）与白蛋白商（Q白蛋白）相关联，以评估其与血液-CSF屏障功能的关系。我们还比较了aSyn与其他几种中枢或外周来源（或两者）的CSF成分，包括白蛋白、神经元特异性烯醇化酶、b-痕量蛋白和总蛋白含量。最后，我们检查aSyn是否存在于脉络丛（CP）的结构内。我们观察到QaSyn不随Q白蛋白值（血-CSF屏障完整性的相对量度）而升高或降低。在我们的CSF梯度分析中，aSyn水平从头侧到尾侧部分略有下降，与神经元特异性烯醇化酶的记录变化平行;总蛋白、白蛋白和b-痕量蛋白的记录趋势相反。后者在尾部CSF组分中显示出较高的浓度，这是由于蛋白质从血液和软脑膜扩散介导转移到脊柱下部区域的CSF中。在人脑的尸检切片中，我们在诊断为一系列神经系统疾病的患者中检测到CP上皮细胞层内高度可变的aSyn反应性;然而，在仅表达人SNCA等位基因的小鼠切片中（以及在没有任何Snca基因表达的小鼠切片中），我们在CP上皮细胞中未检测到aSyn信号。我们从这些补充结果得出结论，尽管其在外周血产物中的水平较高，但脑和脊髓的神经元代表人CSF中aSyn的主要来源。
The source of Parkinson disease-linked a-syn-uclein (aSyn) in human cerebrospinal fluid (CSF) remains unknown. We decided to measure the concentration of aSyn and its gradient in human CSF specimens and compared it with serum to explore its origin. We correlated aSyn concentrations in CSF versus serum (Q aSyn) to the albumin quotient (Q albumin) to evaluate its relation to blood–CSF barrier function. We also compared aSyn with several other CSF constituents of either central or peripheral sources (or both) including albumin, neuron-specific enolase, b-trace protein and total protein content. Finally, we examined whether aSyn is present within the structures of the choroid plexus (CP). We observed that Q aSyn did not rise or fall with Q albumin values, a relative measure of blood–CSF barrier integrity. In our CSF gradient analyses, aSyn levels decreased slightly from rostral to caudal fractions , in parallel to the recorded changes for neuron-specific enolase; the opposite trend was recorded for total protein, albumin and b-trace protein. The latter showed higher concentrations in caudal CSF fractions due to the diffusion-mediated transfer of proteins from blood and leptomeninges into CSF in the lower regions of the spine. In postmortem sections of human brain, we detected highly variable aSyn reactivity within the epithelial cell layer of CP in patients diagnosed with a range of neurological diseases; however, in sections of mice that express only human SNCA alleles (and in those without any Snca gene expression), we detected no aSyn signal in the epithelial cells of the CP. We conclude from these complementary results that despite its higher levels in peripheral blood products, neurons of the brain and spinal cord represent the principal source of aSyn in human CSF.
影响因子：
6
作者：
Schlossmacher, MG;Frosch, MP;Kosik, KS
通讯作者：
Kosik, KS
影响因子：
3.5
作者：
Kuo, Yien-Ming;Li, Zhishan;Nussbaum, Robert L.
通讯作者：
Nussbaum, Robert L.