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血清和脑脊液中 ATP13A2 水平在特发性帕金森病患者中的变化。

ATP13A2 levels in serum and cerebrospinal fluid in patients with idiopathic Parkinson's disease.

机构信息

Reial Acadèmia de Medicina de Catalunya, 08010, Barcelona, Spain; Red Andaluza de Investigación Clínica y Traslacional en Neurología (Neuro-RECA), Laboratorio de Medicina Regenerativa, Hospital Regional Universitario, 29010, Málaga, Spain.

Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario, Instituto de Investigación Biomédica de Málaga (IBIMA), 29010, Málaga, Spain; Red Andaluza de Investigación Clínica y Traslacional en Neurología (Neuro-RECA), Laboratorio de Medicina Regenerativa, Hospital Regional Universitario, 29010, Málaga, Spain.

出版信息

Parkinsonism Relat Disord. 2021 Jul;88:3-9. doi: 10.1016/j.parkreldis.2021.05.014. Epub 2021 May 26.

Abstract

BACKGROUND

The enzyme ATP13A2 holds promise as biomarker in Parkinson's disease (PD). No study has examined the content of ATP13A2 in serum and cerebrospinal fluid (CSF) in idiopathic PD cohorts, or how ATP13A2 relates to the clinical features of the disease.

METHODS

ATP13A2 concentration was evaluated with ELISA and immunoblotting. Correlations of serum and CSF ATP13A2 with clinical parameters were examined. The antiparkinsonian medication regimen was expressed as levodopa equivalent dose (LED, mg/day).

RESULTS

Serum ATP13A2 concentration was similar in patients and controls, and it correlated with LED and MDS-UPDRS part-IV score (p < .0001), a scale which allows evaluating motor complications. LED also correlated with MDS-UPDRS part-IV score (p < .0001). Serum ATP13A2 concentration and LED were higher in patients with motor complications than in patients without motor complications (p < .0001). The ratio of serum ATP13A2 concentration versus LED was calculated, and mean value was similar in patients with or without motor complications. ATP13A2 concentration in the CSF was undetectable in many subjects because the ELISA assay was hampered by its detection limit. Immunoblotting indicated that CSF ATP13A2 content was higher in patients relative to controls (p = .0002), and no clinical correlations were found.

CONCLUSIONS

Increasing LED enhanced serum ATP13A2 concentration and facilitated the development of motor complications. There is a direct relationship between serum ATP13A2 level and the dose intensity of the antiparkinsonian dopaminergic medication. The associations between serum ATP13A2 and LED suggest that serum ATP13A2 content might be a marker of dopamine replacement therapy.

摘要

背景

ATP13A2 酶有望成为帕金森病(PD)的生物标志物。尚无研究检测特发性 PD 队列中血清和脑脊液(CSF)中的 ATP13A2 含量,以及 ATP13A2 与疾病临床特征的关系。

方法

采用 ELISA 和免疫印迹法评估 ATP13A2 浓度。检测血清和 CSF ATP13A2 与临床参数的相关性。抗帕金森病药物方案用左旋多巴等效剂量(LED,mg/天)表示。

结果

患者和对照组的血清 ATP13A2 浓度相似,与 LED 和 MDS-UPDRS 第四部分评分(p<0.0001)相关,该评分可用于评估运动并发症。LED 也与 MDS-UPDRS 第四部分评分相关(p<0.0001)。有运动并发症的患者血清 ATP13A2 浓度和 LED 高于无运动并发症的患者(p<0.0001)。计算血清 ATP13A2 浓度与 LED 的比值,有或无运动并发症的患者平均值相似。由于 ELISA 检测限的限制,许多患者的 CSF 中 ATP13A2 浓度无法检测到。免疫印迹法表明,与对照组相比,患者的 CSF ATP13A2 含量更高(p=0.0002),但未发现临床相关性。

结论

增加 LED 会增加血清 ATP13A2 浓度并促进运动并发症的发生。血清 ATP13A2 水平与抗帕金森病多巴胺能药物的剂量强度直接相关。血清 ATP13A2 与 LED 之间的关联表明,血清 ATP13A2 含量可能是多巴胺替代治疗的标志物。

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