Department of Chemical Engineering, Box 876106, Arizona State University, Tempe, AZ 85287, USA.
Integr Biol (Camb). 2011 Dec;3(12):1188-96. doi: 10.1039/c1ib00018g. Epub 2011 Nov 10.
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.
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极其重要的特征，因此，对参与这些疾病的特定关键形式和形态的脑脊液浓度谱进行特征描述，包括β-淀粉样蛋白（Aβ）和α-突触核蛋白（a-syn），可以作为这些疾病的有效诊断检测方法。脑脊液中的 tau 和 Aβ 水平已被证明作为阿尔茨海默病的生物标志物具有很大的潜力。然而，由于许多神经退行性疾病的发病和进展与包括各种 Aβ 和 a-syn 聚集物在内的可溶性寡聚体蛋白的存在密切相关，因此在 CSF 中特异性检测和定量每种不同的毒性蛋白的水平，可能提供一种简单而准确的方法，用于进行疾病的亚临床诊断和区分。在这里，我们表明，使用高度选择性的形态特异性试剂与敏感的电子生物传感器结合，可以很容易地检测到人 CSF 样本中不同的蛋白质形态。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 CSF 样本。这些研究表明，检测特定的寡聚体聚集物作为神经退行性疾病的敏感生物标志物具有很大的潜力。
