Chen Nai-Ching, Chen Hsiu-Ling, Li Shau-Hsuan, Chang Yen-Hsiang, Chen Meng-Hsiang, Tsai Nai-Wen, Yu Chiun-Chieh, Yang Shieh-Yueh, Lu Cheng-Hsien, Lin Wei-Che
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Front Aging Neurosci. 2020 Apr 28;12:112. doi: 10.3389/fnagi.2020.00112. eCollection 2020.
In this study, we assessed plasma biomarkers to identify cognitive impairment in Parkinson's disease (PD) patients by applying ultra-sensitive immunomagnetic reduction-based immunoassay (IMR).
The study enrolled 60 PD patients and 28 age- and sex-matched normal controls. Complete cognitive function assessments were performed on participants using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating. PD patients with an MMSE score of ≦26 were defined as having cognitive impairment. Meanwhile, a 99mTc-TRODAT-1 scan was performed and plasma levels of Aβ-40, Aβ-42, T-tau, and α-synuclein were evaluated using IMR, subsequent correlation analyses were then performed.
Compared with normal adults, PD patients have higher plasma levels of α-synuclein and T-tau, and a lower level of Aβ-40 ( < 0.05). Plasma levels of α-synuclein ( = -0.323, = 0.002), Aβ-40 ( = 0.276, = 0.01), and T-tau ( = -0.322, = 0.002) are significantly correlated with MMSE scores. The TRODAT scan results, including visual inspection and quantification, revealed significant correlations between Aβ-40 and PD. Multiple regression analysis showed that the plasma levels of Aβ-40 (OR = 0.921, 95% CI = 0.879-0.962), α-synuclein (OR = 3.016, 95% CI = 1.703-5.339), and T-tau (OR = 1.069, 95% CI = 1.026-1.115) were independently associated with PD patients with cognitive impairment. The cutoff values for predicting cognitive deficits in PD patients were 45.101 pg/ml of Aβ-40, (Area under curve (AUC) = 0.791), 0.389 pg/ml of α-synuclein, (AUC = 0.790), and 30.555 pg/ml of T-tau (AUC = 0.726).
Plasma levels of α-synuclein, Aβ-40, and T-tau are potential biomarkers to detect cognitive impairment in PD patients.
在本研究中,我们通过应用基于超灵敏免疫磁珠还原的免疫分析方法(IMR)评估血浆生物标志物,以识别帕金森病(PD)患者的认知障碍。
该研究纳入了60例PD患者和28例年龄及性别匹配的正常对照。使用简易精神状态检查表(MMSE)和临床痴呆评定量表对参与者进行全面的认知功能评估。MMSE评分≤26分的PD患者被定义为有认知障碍。同时,进行了99mTc-TRODAT-1扫描,并使用IMR评估血浆中Aβ-40、Aβ-42、总tau蛋白(T-tau)和α-突触核蛋白的水平,随后进行相关性分析。
与正常成年人相比,PD患者血浆中α-突触核蛋白和T-tau水平较高,Aβ-40水平较低(P<0.05)。α-突触核蛋白(r=-0.323,P=0.002)、Aβ-40(r=0.276,P=0.01)和T-tau(r=-0.322,P=0.002)的血浆水平与MMSE评分显著相关。TRODAT扫描结果,包括视觉检查和定量分析,显示Aβ-40与PD之间存在显著相关性。多元回归分析表明,Aβ-40(比值比(OR)=0.921,95%置信区间(CI)=0.879-0.962)、α-突触核蛋白(OR=3.016,95%CI=1.703-5.339)和T-tau(OR=1.069,95%CI=1.026-1.115)的血浆水平与有认知障碍的PD患者独立相关。预测PD患者认知缺陷的截断值分别为:Aβ-40为45.101 pg/ml(曲线下面积(AUC)=0.791),α-突触核蛋白为0.389 pg/ml(AUC=0.790),T-tau为30.555 pg/ml(AUC=0.726)。
α-突触核蛋白、Aβ-40和T-tau的血浆水平是检测PD患者认知障碍的潜在生物标志物。