帕金森病中的神经炎症：一项使用[C]PBR28正电子发射断层扫描和脑脊液标志物的研究。

Neuroinflammation in Parkinson's disease: A study with [C]PBR28 PET and cerebrospinal fluid markers.

作者信息

Al-Abdulrasul H, Ajalin R, Tuisku J, Zetterberg H, Blennow K, Vahlberg T, Ekblad L, Helin S, Forsback S, Rinne J O, Brück A

机构信息

Turku PET Centre, University of Turku, Turku, Finland; Department of Neurology, Helsinki University Hospital, Helsinki, Finland; Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland.

Turku PET Centre, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.

出版信息

Parkinsonism Relat Disord. 2025 Jan;130:107177. doi: 10.1016/j.parkreldis.2024.107177. Epub 2024 Oct 25.

DOI:10.1016/j.parkreldis.2024.107177

PMID:39531949

Abstract

OBJECTIVE

To investigate neuroinflammation in Parkinson's disease (PD) with [C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[F]-fluoro-L-dopa ([F]FDOPA) PET.

METHODS

The clinical cohort consisted of 20 subjects with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [C]PBR28 High Resolution Research Tomograph (HRRT) PET for the quantitative assessment of cerebral binding to the translocator protein (TSPO), a neuroinflammation marker. CSF samples were available from 17 subjects with PD and 21 HC and were examined for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), neurogranin (NG), alpha-synuclein (aSyn) and oligo-alpha-synuclein. All subjects with PD underwent [F]FDOPA HRRT PET.

RESULTS

While the subjects with PD and HC did not differ in the total volume of distribution (V) of [C]PBR28 in any studied brain regions, higher levels of neuroinflammation and neurodegeneration CSF biomarkers sTREM2 and NG, respectively were associated with more severe motor symptoms evaluated by The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) (r = 0.52, p = 0.041 and r = 0.59, p = 0.016 respectively). Additionally, in the PD group increased [C]PBR28 V in the basal ganglia and substantia nigra (SN) was related to higher levels of neuroinflammation biomarker YKL-40 (p < 0.01).

CONCLUSION

Associations between CSF biomarkers, motor disability and [C]PBR28 V in the striatum and SN may support a role for neuroinflammation in PD.

摘要

目的

采用[C]PBR28正电子发射断层扫描（PET）和脑脊液（CSF）生物标志物研究帕金森病（PD）中的神经炎症，以及与用6-[F]-氟-L-多巴（[F]FDOPA）PET测量的多巴胺能功能的关系。

方法

临床队列包括20例PD患者和51名健康对照（HC）。所有HC和15例PD参与者均接受了[C]PBR28高分辨率研究断层扫描仪（HRRT）PET检查，以定量评估大脑与转运体蛋白（TSPO）的结合情况，TSPO是一种神经炎症标志物。17例PD患者和21名HC的CSF样本可获取，并检测了髓样细胞上表达的可溶性触发受体2（sTREM2）、几丁质酶3样1蛋白（YKL-40）、神经颗粒素（NG）、α-突触核蛋白（aSyn）和寡聚α-突触核蛋白。所有PD患者均接受了[F]FDOPA HRRT PET检查。

结果

虽然PD患者和HC在任何研究脑区的[C]PBR28分布总体积（V）上无差异，但神经炎症和神经退行性变的CSF生物标志物sTREM2和NG水平升高分别与统一帕金森病评定量表运动部分（UPDRS-III）评估的更严重运动症状相关（r = 0.52，p = 0.041和r = 0.59，p = 0.016）。此外，在PD组中，基底神经节和黑质（SN）中[C]PBR28 V增加与神经炎症生物标志物YKL-40水平升高相关（p < 0.01）。