The diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) can only be confirmed by abnormal protease-resistant prion protein accumulation in post-mortem brain tissue. The relationships between sCJD and cerebrospinal fluid (CSF) proteins such as 14–3-3, tau, and α-synuclein (a-syn) have been investigated for their potential value in pre-mortem diagnosis. Recently, deep-learning (DL) methods have attracted attention in neurodegenerative disease research. We established DL-aided pre-mortem diagnostic methods for CJD using multiple CSF biomarkers to improve their discriminatory sensitivity and specificity. Enzyme-linked immunosorbent assays were performed on phospho-tau (p-tau), total-tau (t-tau), a-syn, and β-amyloid (1–42), and western blot analysis was performed for 14–3-3 protein from CSF samples of 49 sCJD and 256 non-CJD Korean patients, respectively. The deep neural network structure comprised one input, five hidden, and one output layers, with 20, 40, 30, 20 and 12 hidden unit numbers per hidden layer, respectively. The best performing DL model demonstrated 90.38% accuracy, 83.33% sensitivity, and 92.5% specificity for the three-protein combination of t-tau, p-tau, and a-syn, and all other patients in a separate CSF set (n = 15) with other neuronal diseases were correctly predicted to not have CJD. Thus, DL-aided pre-mortem diagnosis may provide a suitable tool for discriminating CJD patients from non-CJD patients.

散发性Creutzfeldt-Jakob病（sCJD）的诊断只能通过验尸后脑组织中蛋白酶抗性蛋白的异常积累来确定。已经研究了sCJD与脑脊液（CSF）蛋白（如14–3-3，tau和α-突触核蛋白（a-syn））之间的关系，以确定它们在死前诊断中的潜在价值。近年来，深度学习（DL）方法已引起神经退行性疾病研究的关注。我们使用多种CSF生物标记物建立了DL辅助的CJD死前诊断方法，以提高其鉴别敏感性和特异性。酶联免疫吸附测定分别在磷酸化tau（p-tau），总tau（t-tau），a-syn和β-淀粉样蛋白（1-42）上进行，并且western blot分析用于14-3来自49 sCJD和256名非CJD韩国患者的CSF样本中的-3蛋白，分别。深度神经网络结构包括一个输入层，五个隐藏层和一个输出层，每个隐藏层分别具有20、40、30、20和12个隐藏单元号。表现最佳的DL模型对t-tau，p-tau和a-syn的三种蛋白质组合以及单独的CSF组中的所有其他患者显示出90.38％的准确性，83.33％的敏感性和92.5％的特异性（n = 15）与其他神经元疾病被正确预测为无CJD。因此，DL辅助的验前诊断可以提供一种合适的工具，以区分CJD患者和非CJD患者。正确预测t-tau，p-tau和a-syn的三种蛋白质组合具有5％的特异性，以及单独的CSF组（n = 15）中与其他神经元疾病有关的所有其他患者没有CJD。因此，DL辅助的验尸诊断可以提供一种区分CJD患者和非CJD患者的合适工具。正确预测t-tau，p-tau和a-syn的三种蛋白质组合具有5％的特异性，以及单独的CSF组（n = 15）中与其他神经元疾病有关的所有其他患者没有CJD。因此，DL辅助的验尸诊断可以提供一种区分CJD患者和非CJD患者的合适工具。