CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease.
CSF levels of oligomeric alpha-synuclein and beta-amyloid as biomarkers for neurodegenerative disease.
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DOI：
10.1039/c1ib00018g
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Prasad S
中科院分区：
文献类型：
--
作者：
Sierks MR;Chatterjee G;McGraw C;Kasturirangan S;Schulz P;Prasad S
蛋白质错误折叠和聚集是许多破坏性神经退行性疾病的一个至关重要的特征，因此表征与这些疾病有关的蛋白质的选择关键形式和形态的脑脊液浓度谱，包括β-淀粉样蛋白（a β）和α-突触核蛋白（a-syn），可以有效地诊断这些疾病。脑脊液中tau和Aβ的水平已被证明有很大的希望作为阿尔茨海默病的生物标志物。然而，由于许多神经退行性疾病的发生和进展与可溶性寡聚蛋白（包括各种a β和a-syn聚集物）的存在密切相关，特异性检测和定量CSF中每种不同毒性蛋白的水平可能为症状前诊断和区分这些疾病提供一种简单而准确的方法。在这里，我们展示了人类脑脊液样品中不同蛋白质形态的存在，可以很容易地使用高选择性形态特异性试剂与敏感的电子生物传感器相结合来检测。我们进一步表明，这些形态特异性试剂可以很容易地区分来自AD， PD和认知正常来源的死后脑脊液样本。这些研究表明，检测特定的寡聚物聚集体作为神经退行性疾病的敏感生物标志物具有很大的前景。
Protein misfolding and aggregation is a critically important feature in many devastating neurodegenerative diseases, therefore characterization of the CSF concentration profiles of selected key forms and morphologies of proteins involved in these diseases, including β-amyloid (Aβ) and α-synuclein (a-syn), can be an effective diagnostic assay for these diseases. CSF levels of tau and Aβ have been shown to have great promise as biomarkers for Alzheimer’s disease. However since the onset and progression of many neurodegenerative diseases have been strongly correlated with the presence of soluble oligomeric aggregates of proteins including various Aβ and a-syn aggregate species, specific detection and quantification of levels of each of these different toxic protein species in CSF may provide a simple and accurate means to presymptomatically diagnose and distinguish between these diseases. Here we show that the presence of different protein morphologies in human CSF samples can be readily detected using highly selective morphology specific reagents in conjunction with a sensitive electronic biosensor. We further show that these morphology specific reagents can readily distinguish between post-mortem CSF samples from AD, PD and cognitively normal sources. These studies suggest that detection of specific oligomeric aggregate species holds great promise as sensitive biomarkers for neurodegenerative disease.
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影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
2.4
作者：
Barkhordarian, Hedieh;Emadi, Sharareh;Sierks, Michael R.
通讯作者：
Sierks, Michael R.
DOI：
10.1073/pnas.97.2.571
发表时间：
2000-01-18
影响因子：
11.1
作者：
Conway, KA;Lee, SJ;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
25
作者：
Cleary, JP;Walsh, DM;Ashe, KH
通讯作者：
Ashe, KH