认知功能正常的帕金森病患者自然人群中的脑脊液阿尔茨海默病生物标志物与血脑屏障完整性。
Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients.
机构信息
Department of Systems Medicine, Neurophysiopathology Unit, University of Rome "Tor Vergata", Rome. Italy.
Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.
出版信息
CNS Neurol Disord Drug Targets. 2017;16(3):339-345. doi: 10.2174/1871527316666161205123123.
BACKGROUND
Cerebrospinal-fluid (CSF) Alzheimer's Disease (AD) biomarkers have been extensively studied in Parkinson's Disease (PD). Although reduced CSF beta-amyloid1-42 (Aβ42) levels have been associated with cognitive decline in PD, the alteration of CSF tau proteins remains controversial. In addition, the impairment of the blood-brain barrier (BBB) has been previously demonstrated along the PD progression.
OBJECTIVE
The aim of the present study was to assess CSF AD biomarkers and BBB integrity in a natural cohort of cognitive intact PD patients compared to matched controls.
METHOD
We measured and correlated CSF AD biomarkers and CSF/serum albumin ratio (expression of BBB integrity) in 124 PD patients and 46 controls. We distributed PD patients in three subgroups based on the Hoehn and Yahr (H&Y) staging: mild PD (1-1.5, n=40); moderate PD (2-2.5, n=58); advanced PD (3-5, n=26). PD patients were also distinguished as tremor dominant (TD, n=44) and non-tremor dominant (NTD, n=80).
RESULTS
PD patients showed lower CSF Aβ42 levels and higher CSF/serum albumin ratio compared to controls. CSF total tau (t-tau) concentrations as well as the CSF/serum albumin ratio gradually increased among H&Y stages. Conversely, we did not find differences between TD and NTD patients. Significantly, we documented the positive correlation between CSF t-tau levels and both CSF/serum albumin ratio and motor impairment in PD patients.
CONCLUSION
This study performed in cognitive intact PD patients confirms the progressive increase of CSF tau proteins levels and BBB impairment along with the evolution of PD pathology. Since the BBB ensures the clearance of tau proteins from brain, we hypothesize that the dysfunction of the BBB throughout the disease progression may possibly cause the concurrent increase of CSF tau proteins levels in PD, which could be irrespective of cognitive decline.
背景
脑脊髓液（CSF）阿尔茨海默病（AD）生物标志物已在帕金森病（PD）中进行了广泛研究。尽管 CSF 中β-淀粉样蛋白 1-42（Aβ42）水平降低与 PD 认知能力下降有关，但 CSF 中的 tau 蛋白的改变仍存在争议。此外，之前已经证明 PD 进展过程中血脑屏障（BBB）受损。
目的
本研究旨在评估认知正常的 PD 患者与匹配对照组相比，其 CSF AD 生物标志物和 BBB 完整性。
方法
我们测量并分析了 124 例 PD 患者和 46 例对照组的 CSF AD 生物标志物和 CSF/血清白蛋白比值（BBB 完整性的表达）。我们根据 Hoehn 和 Yahr（H&Y）分期将 PD 患者分为三组：轻度 PD（1-1.5，n=40）；中度 PD（2-2.5，n=58）；晚期 PD（3-5，n=26）。PD 患者还分为震颤主导型（TD，n=44）和非震颤主导型（NTD，n=80）。
结果
PD 患者的 CSF Aβ42 水平低于对照组，而 CSF/血清白蛋白比值高于对照组。CSF 总 tau（t-tau）浓度以及 CSF/血清白蛋白比值随着 H&Y 分期逐渐升高。相反，我们没有发现 TD 和 NTD 患者之间的差异。值得注意的是，我们记录了 PD 患者 CSF t-tau 水平与 CSF/血清白蛋白比值和运动障碍之间的正相关。
结论
这项在认知正常的 PD 患者中进行的研究证实，随着 PD 病理学的发展，CSF tau 蛋白水平逐渐升高，BBB 受损。由于 BBB 可确保 tau 蛋白从大脑中清除，我们假设，随着疾病的进展，BBB 功能障碍可能会导致 PD 患者 CSF tau 蛋白水平的同时升高，这可能与认知能力下降无关。
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