Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease
Evolution of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in Early Parkinson's Disease
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DOI：
10.1002/ana.25811
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发表时间：
2020-07-02
影响因子：
11.2
通讯作者：
Shaw, Leslie M.
中科院分区：
文献类型：
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作者：
Irwin, David J.;Fedler, Janel;Shaw, Leslie M.
目的分析早期帕金森病(PD)患者阿尔茨海默病(AD)患者脑脊液(CSF)生物标志物的纵向分布特征，并检测基线脑脊液(CSF)生物标志物对帕金森病(PD)患者病情下降的预测作用。方法采用高精度罗氏电化学发光免疫分析法检测416例PD患者和192例HCS患者脑脊液中苏氨酸181位Aβ1~42(Aβ42)、总tau(t-tau)和磷酸化tau(p-tau)的含量，并进行为期3年的帕金森进展指数(PMI)监测。采用线性混合效应模型对纵向脑脊液和临床资料进行分析。结果基线时PD患者脑脊液t-tau(中位数=157.7 pg/m L；范围=80.9~467.0)、p-tau(中位数=13.4pg/m L；范围=8.0~40.1)和Aβ(42)(中位数=846.2 pg/m L；范围=238.8-3,707.0)均低于正常对照组(脑脊液t-tau中位数=173.5 pg/m L；范围=82.0~580.8；p-tau中位数=15.4pg/m L；Aβ(42)中位数=926.5 pg/m L；范围=239.1-3,297.0；p<；0.05-0.001)，在PD和HCS患者中，这些生物标记物之间存在中到强的相关性(rho=0.5-0.97；p<；0.001)。在PD患者中，31.5%的患者在基线水平时脑脊液Aβ水平(42)处于病理性低水平，这些PD患者的p-tau水平较低(中位数=10.8pg/mL；范围=8.0-32.8)，相比之下，27.7%的HCS患者的脑脊液Aβ水平(42)(脑脊液p-tau中位数=12.8pg/mL；范围8.2-73.6；p<；在纵向脑脊液分析中，我们发现帕金森病患者3年时脑脊液Aβ(42)(平均差值=-41.83 pg/m L；p=0.03)和脑脊液p-tau(平均差值=-0.38 pg/m L；p=0.03)较HCS患者有更大的下降。基线脑脊液Aβ(42)值预示着早期帕金森病患者认知、自主神经和运动功能的轻微但可测量的下降。我们的数据提示基线脑脊液AD生物标记物可能对早期帕金森病有预后价值，这些标记物的动态变化，尽管在3年期间变化不大，但提示帕金森病患者的生物标记物谱可能偏离健康老龄化。Ann Neurol 2020
Objective We analyzed the longitudinal profile of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers in early Parkinson's disease (PD) compared with healthy controls (HCs) and tested baseline CSF biomarkers for prediction of clinical decline in PD. Methods Amyloid-beta 1 to 42 (A beta(42)), total tau (t-tau) and phosphorylated tau (p-tau) at the threonine 181 position were measured using the high-precision Roche Elecsys electrochemiluminescence immunoassay in all available CSF samples from longitudinally studied patients with PD (n = 416) and HCs (n = 192) followed for up to 3 years in the Parkinson's Progression Markers Initiative (PPMI). Longitudinal CSF and clinical data were analyzed with linear-mixed effects models. Results We found patients with PD had lower CSF t-tau (median = 157.7 pg/mL; range = 80.9-467.0); p-tau (median = 13.4 pg/mL; range = 8.0-40.1), and A beta(42)(median = 846.2 pg/mL; range = 238.8-3,707.0) than HCs at baseline (CSF t-tau median = 173.5 pg/mL; range = 82.0-580.8; p-tau median = 15.4 pg/mL; range = 8.1-73.6; and A beta(42)median = 926.5 pg/mL; range = 239.1-3,297.0;p< 0.05-0.001) and a moderate-to-strong correlation among these biomarkers in both patients with PD and HCs (Rho = 0.50-0.97;p< 0.001). Of the patients with PD, 31.5% had pathologically low levels of CSF A beta(42)at baseline and these patients with PD had lower p-tau levels (median = 10.8 pg/mL; range = 8.0-32.8) compared with 27.7% of HCs with pathologically low CSF A beta(42)(CSF p-tau median = 12.8 pg/mL; range 8.2-73.6;p< 0.03)(.)In longitudinal CSF analysis, we found patients with PD had greater decline in CSF A beta(42)(mean difference = -41.83 pg/mL;p= 0.03) and CSF p-tau (mean difference = -0.38 pg/mL;p= 0.03) at year 3 compared with HCs. Baseline CSF A beta(42)values predicted small but measurable decline on cognitive, autonomic, and motor function in early PD. Interpretation Our data suggest baseline CSF AD biomarkers may have prognostic value in early PD and that the dynamic change of these markers, although modest over a 3-year period, suggest biomarker profiles in PD may deviate from healthy aging. ANN NEUROL 2020