帕金森病中脑葡萄糖代谢和神经退行性变的生物标志物：一项基于脑脊液的研究。

Biomarkers of Cerebral Glucose Metabolism and Neurodegeneration in Parkinson's Disease: A Cerebrospinal Fluid-Based Study.

作者信息

Liguori Claudio, Stefani Alessandro, Fernandes Mariana, Cerroni Rocco, Mercuri Nicola Biagio, Pierantozzi Mariangela

机构信息

Neurology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Italy.

Sleep Medicine Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Italy.

出版信息

J Parkinsons Dis. 2022;12(2):537-544. doi: 10.3233/JPD-212936.

DOI:10.3233/JPD-212936

PMID:34864690

Abstract

BACKGROUND

Several biomarkers have been evaluated in Parkinson's disease (PD); cerebrospinal fluid (CSF) levels of lactate may reflect cerebral metabolism function and CSF amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) concentrations may detect an underlying neurodegenerative process.

OBJECTIVE

CSF levels of lactate, Aβ42, t-tau, and p-tau were measured in patients with mild to moderate PD. CSF levels of dopamine (DA) and its metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) were also assessed, exploring their relations with the other CSF biomarkers.

METHODS

101 drug-naive PD patients and 60 controls were included. Participants underwent clinical assessments and CSF biomarker analysis. Patients were divided into subgroups according to their Hoehn & Yahr stage (PD-1, PD-2, PD-3).

RESULTS

PD patients showed higher lactate levels (M = 1.91; p = 0.03) and lower Aβ42 (M = 595; p < 0.001) and DA levels (M = 0.32; p = 0.04) than controls (Mlactate = 1.72; MAβ42 = 837; MDA = 0.50), while no significant differences were found in t-tau, p-tau and DOPAC concentrations. Considering the subgroup analysis, PD-3 group had higher lactate (M = 2.12) and t-tau levels (M = 333) than both PD-1 (Mlactate = 1.75, p = 0.006; Mt - tau = 176, p = 0.008) and PD-2 groups (Mlactate = 1.91, p = 0.01; Mt - tau = 176, p = 0.03), as well as the controls (Mlactate = 1.72, p = 0.04; Mt - tau = 205, p = 0.04). PD-2 group showed higher lactate levels than PD-1 group (p = 0.04) and controls (p = 0.03). Finally, CSF lactate levels negatively correlated with DA (r = -0.42) and positively with t-tau CSF levels (r = 0.33).

CONCLUSION

This CSF-based study shows that lactate levels in PD correlated with both clinical disease progression and neurodegeneration biomarkers, such as tau proteins and DA. Further studies should explore the clinical potential of measuring CSF biomarkers for better understanding the role of brain energy metabolism in PD, for research and therapeutic options.

摘要

背景

已经在帕金森病（PD）中评估了几种生物标志物；脑脊液（CSF）中的乳酸水平可能反映脑代谢功能，而CSF淀粉样蛋白-β42（Aβ42）、总tau蛋白（t-tau）和磷酸化tau蛋白（p-tau）的浓度可能检测潜在的神经退行性过程。

目的

测量轻度至中度PD患者CSF中乳酸、Aβ42、t-tau和p-tau的水平。还评估了CSF中多巴胺（DA）及其代谢产物3,4-二羟基苯乙酸（DOPAC）的水平，探讨它们与其他CSF生物标志物的关系。

方法

纳入101例未服用过药物的PD患者和60例对照。参与者接受临床评估和CSF生物标志物分析。根据Hoehn & Yahr分期将患者分为亚组（PD-1、PD-2、PD-3）。

结果

与对照组（乳酸M=1.72；Aβ42 M=837；DA M=0.50）相比，PD患者的乳酸水平更高（M=1.91；p=0.03），Aβ42和DA水平更低（Aβ42 M=595；p<0.001；DA M=0.32；p=0.04），而t-tau、p-tau和DOPAC浓度无显著差异。考虑亚组分析，PD-3组的乳酸（M=2.12）和t-tau水平（M=333）高于PD-1组（乳酸M=1.75，p=0.006；t-tau M=176，p=0.008）和PD-2组（乳酸M=1.91，p=0.01；t-tau M=176，p=0.03）以及对照组（乳酸M=1.72，p=0.04；t-tau M=205，p=0.04）。PD-2组的乳酸水平高于PD-1组（p=0.04）和对照组（p=0.03）。最后CSF乳酸水平与DA呈负相关（r=-0.42），与CSF中t-tau水平呈正相关（r=0.33）。