Department of Neurology, Institute of Neuroscience and Physiology at Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Acta Neurol Scand. 2019 Aug;140(2):147-156. doi: 10.1111/ane.13116. Epub 2019 May 20.
Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders.
To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders.
Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors.
NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P < 0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P = 0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P = 0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P = 0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P = 0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P < 0.001).
NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies.
帕金森病患者的死亡率增加，帕金森病（PD）患者死亡率中等，而非典型帕金森病患者（APD）死亡率明显增加，包括多系统萎缩（MSA）、进行性核上性麻痹（PSP）和皮质基底变性（CBD）。然而，目前尚无可靠的定量生物标志物可用于预测死亡率。脑脊液（CSF）神经退行性变生物标志物，如神经丝轻链（NF-L）、总tau（t-tau）和tau 病理学标志物磷酸化 tau（p-tau）与其他神经退行性疾病（如肌萎缩侧索硬化症、阿尔茨海默病）的死亡率相关，但尚未在帕金森病患者中进行相关研究。
研究帕金森病患者脑脊液（CSF）生物标志物（NF-L、t-tau 和 p-tau）与死亡率的关系。
收集了 68 例 PD 和 83 例 APD 患者的人口统计学、死亡率和 CSF 数据。使用 Cox 回归进行生存分析，以腰椎穿刺时的年龄、性别、诊断和 CSF 生物标志物水平为预测因子。
CSF 中的 NF-L 与突触核蛋白病（PD、MSA；HR 3.698 [2.196-6.228，95%置信区间（CI）]，P<0.001）、PSP（HR 2.767 [1.126-6.802 95% CI]，P=0.027）和整个队列（HR 1.661 [1.082-2.55，95% CI]，P=0.02）的死亡率增加相关。CSF 中的 t-tau 与 PSP 患者的死亡率增加相关（HR 9.587 [1.143-80.418]，P=0.037）。CSF 中的 p-tau 与突触核蛋白病患者的死亡率降低相关（HR 0.196 [0.041-0.929，95% CI]，P=0.040）。非典型帕金森病和tau 病与更高的死亡率相关（HR 8.798 [4.516-17.14，95% CI]和 HR 3.040 [1.904-4.854]，P<0.001）。
CSF 中的 NF-L 和 tau 蛋白可能有助于预测帕金森病患者的死亡率，应在更大规模的研究中进行进一步研究。
