Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies.
Post mortem cerebrospinal fluid α-synuclein levels are raised in multiple system atrophy and distinguish this from the other α-synucleinopathies, Parkinson's disease and Dementia with Lewy bodies.
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DOI：
10.1016/j.nbd.2011.08.003
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发表时间：
2012-01
影响因子：
6.1
通讯作者：
Mann, D. M. A.
中科院分区：
文献类型：
--
作者：
Foulds, P. G.;Yokota, O.;Thurston, A.;Davidson, Y.;Ahmed, Z.;Holton, J.;Thompson, J. C.;Akiyama, H.;Arai, T.;Hasegawa, M.;Gerhard, A.;Allsop, D.;Mann, D. M. A.
关键词：
在临床上区分帕金森病（PD）和进行性核上性麻痹（PSP）、皮质基底综合征（CBS）和多系统萎缩（MSA）等非典型帕金森综合征具有挑战性，但对于患者管理和临床试验招募至关重要。因为PD（以及相关的路易体痴呆（DLB））和MSA的特征在于α-突触核蛋白蛋白（α-syn）的聚集形式在脑中的沉积，而CBS和PSP是tau蛋白病，我们已经开发了免疫测定来检测体液中α-syn的总形式和寡聚形式以及α-syn的磷酸化和磷酸化寡聚形式的水平，试图找到一种生物标志物来区分这些疾病。检测了76例PD、DLB、PSP或MSA患者和20例健康对照者的脑室脑脊液（CSF）中这4种不同形式的α-syn水平。总α-syn和寡聚α-syn以及磷酸化α-syn的平均CSF水平在诊断组之间没有显著差异，而磷酸化寡聚α-syn的平均CSF水平在不同诊断组之间确实存在显著差异（p < 0.001）。尽管与所有其他诊断组相比，MSA患者的α-syn的所有4项指标均较高，但与所有其他诊断组相比，MSA患者的α-syn磷酸化寡聚体形式仅显著升高（p < 0.001）。这表明，这种特定的测定法可用于区分MSA与对照受试者和患有其他α-突触核蛋白病的患者。然而，它似乎没有帮助区分PD和DLB患者与PSP或对照受试者。蛋白质印迹显示CSF中α-syn的主要形式是磷酸化的，磷酸化寡聚体α-syn免疫测定法似乎是4种测定法中信息量最大的结果与该观察结果一致。
Differentiating clinically between Parkinson's disease (PD) and the atypical parkinsonian syndromes of Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and multiple system atrophy (MSA) is challenging but crucial for patient management and recruitment into clinical trials. Because PD (and the related disorder Dementia with Lewy bodies (DLB)) and MSA are characterised by the deposition of aggregated forms of α-synuclein protein (α-syn) in the brain, whereas CBS and PSP are tauopathies, we have developed immunoassays to detect levels of total and oligomeric forms of α-syn, and phosphorylated and phosphorylated oligomeric forms of α-syn, within body fluids, in an attempt to find a biomarker that will differentiate between these disorders. Levels of these 4 different forms of α-syn were measured in post mortem samples of ventricular cerebrospinal fluid (CSF) obtained from 76 patients with PD, DLB, PSP or MSA, and in 20 healthy controls. Mean CSF levels of total and oligomeric α-syn, and phosphorylated α-syn, did not vary significantly between the diagnostic groups, whereas mean CSF levels of phosphorylated oligomeric α-syn did differ significantly (p < 0.001) amongst the different diagnostic groups. Although all 4 measures of α-syn were higher in patients with MSA compared to all other diagnostic groups, these were only significantly raised (p < 0.001) in MSA compared to all other diagnostic groups, for phosphorylated oligomeric forms of α-syn. This suggests that this particular assay may have utility in differentiating MSA from control subject and patients with other α-synucleinopathies. However, it does not appear to be of help in distinguishing patients with PD and DLB from those with PSP or from control subjects. Western blots show that the principal form of α-syn within CSF is phosphorylated, and the finding that the phosphorylated oligomeric α-syn immunoassay appears to be the most informative of the 4 assays would be consistent with this observation.
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影响因子：
16.2
作者：
Sharon, R;Bar-Joseph, I;Selkoe, DJ
通讯作者：
Selkoe, DJ
DOI：
10.1016/j.bbrc.2007.09.048
发表时间：
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