Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease and affects 1% of the population above 60 years old. Although Parkinson's disease commonly manifests with motor symptoms, a majority of patients with Parkinson's disease subsequently develop cognitive impairment, which often progresses to dementia, a major cause of morbidity and disability. Parkinson's disease is characterized by α-synuclein accumulation that frequently associates with amyloid-β and tau fibrils, the hallmarks of Alzheimer's disease neuropathological changes; this co-occurrence suggests that onset of cognitive decline in Parkinson's disease may be associated with appearance of pathological amyloid-β and/or tau. Recent studies have highlighted the appearance of the soluble form of the triggering receptor expressed on myeloid cells 2 (sTREM2) receptor in CSF during development of Alzheimer's disease. Given the known association of microglial activation with advancing Parkinson's disease, we investigated whether CSF and/or plasma sTREM2 differed between CSF biomarker-defined Parkinson's disease participant subgroups. In this cross-sectional study, we examined 165 participants consisting of 17 cognitively normal elderly subjects, 45 patients with Parkinson's disease with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF amyloid-β and tau levels revealed that CSF sTREM2 concentrations were elevated in Parkinson's disease subgroups with a positive tau CSF biomarker signature, but not in Parkinson's disease subgroups with a positive CSF amyloid-β biomarker signature. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in Parkinson's disease.

中文翻译：

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帕金森病亚组中可溶性 TREM2 升高，脑脊液 tau 蛋白增加。

帕金森病是继阿尔茨海默病之后第二常见的神经退行性疾病，影响 1% 的 60 岁以上人口。尽管帕金森病通常表现为运动症状，但大多数帕金森病患者随后会出现认知障碍，这通常会进展为痴呆，这是发病和残疾的主要原因。帕金森病的特点是 α-突触核蛋白积聚，通常与淀粉样蛋白-β 和 tau 纤维相关，这是阿尔茨海默病神经病理学变化的标志；这种同时发生表明帕金森病认知能力下降的发生可能与病理性β-淀粉样蛋白和/或tau蛋白的出现有关。最近的研究强调了在阿尔茨海默病的发展过程中，脑脊液中骨髓细胞 2 (sTREM2) 受体表达的可溶性触发受体的出现。鉴于已知小胶质细胞激活与帕金森病进展之间的关联，我们研究了 CSF 和/或血浆 sTREM2 在 CSF 生物标志物定义的帕金森病参与者亚组之间是否存在差异。在这项横断面研究中，我们检查了 165 名参与者，其中包括 17 名认知正常的老年受试者、45 名没有认知障碍的帕金森病患者、86 名患有轻度认知障碍的患者和 17 名患有痴呆症的患者。按脑脊液β淀粉样蛋白和tau水平对受试者进行分层显示，在具有阳性tau脑脊液生物标志物特征的帕金森病亚组中，脑脊液sTREM2浓度升高，但在具有阳性脑脊液淀粉样蛋白-β生物标志物特征的帕金森病亚组中则没有升高。这些发现表明，CSF sTREM2 可以作为帕金森病神经元损伤的替代免疫生物标志物。