Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy; Center for Neurodegenerative Disease Research (CESNE), University of Padova, Padova, Italy.
Parkinson and Movement Disorders Unit, Centre for Rare Neurological Diseases (ERN-RND), Department of Neuroscience, University of Padova, Padova, Italy.
Neurobiol Dis. 2024 Oct 1;200:106609. doi: 10.1016/j.nbd.2024.106609. Epub 2024 Jul 22.
Gastrointestinal dysfunction has emerged as a prominent early feature of Parkinson's Disease, shedding new light on the pivotal role of the enteric nervous system in its pathophysiology. However, the role of immune-cell clusters and inflammatory and glial markers in the gut pathogenetic process needs further elucidation.
We aimed to study duodenum tissue samples to characterize PD's enteric nervous system pathology further. Twenty patients with advanced PD, six with early PD, and 18 matched controls were included in the PADUA-CESNE cohort.
Duodenal biopsies from 26 patients with early to advanced stage PD and 18 age-matched HCs were evaluated for the presence of surface markers (CD3+, CD4+, CD8+, CD20+, CD68+, HLA-DR), presence of misfolded alpha-synuclein and enteric glial alteration (GFAP). Correlation of immulogic pattern and clinical characteristic were analyzed.
The findings validate that in patients with Parkinson's Disease, the activation and reactive gliosis are linked to the neurodegeneration triggered by the presence of misfolded alpha-synuclein in the enteric nervous system. This process intensifies from the initial to the advanced stages of the disease. The clusters of T- and B-lymphocytes in the enteric system, along with the overall expression of HLA-DR in antigen-presenting cells, exceeded those in the control group. Conversely, no differences in terms of macrophage populations were found.
These findings broaden our understanding of the mechanisms underlying the enteric nervous system's involvement in PD and point to the gastrointestinal system as a potential therapeutic target, especially in the early stages of the disease. Moreover, our results propose a role of T- and B-lymphocytes in maintaining inflammation and ultimately influencing alpha-synuclein misfolding and aggregation.
胃肠道功能障碍已成为帕金森病的一个突出早期特征，这突显了肠神经系统在其病理生理学中的关键作用。然而，免疫细胞簇、炎症和神经胶质标志物在肠道发病机制中的作用仍需要进一步阐明。
我们旨在研究十二指肠组织样本，以进一步描述 PD 的肠神经系统病理学。PADUA-CESNE 队列纳入了 20 例晚期 PD 患者、6 例早期 PD 患者和 18 名匹配的对照者。
评估了 26 例早期至晚期 PD 患者和 18 名年龄匹配的健康对照者的十二指肠活检标本，以评估表面标志物（CD3+、CD4+、CD8+、CD20+、CD68+、HLA-DR）、错误折叠的α-突触核蛋白和肠神经胶质改变（GFAP）的存在。分析了免疫模式与临床特征的相关性。
这些发现验证了在帕金森病患者中，激活和反应性神经胶质增生与肠神经系统中错误折叠的α-突触核蛋白引发的神经退行性变有关。这一过程从疾病的初始阶段到晚期阶段逐渐加剧。与对照组相比，肠神经系统中的 T 细胞和 B 细胞簇以及抗原呈递细胞中 HLA-DR 的总体表达增加。相反，巨噬细胞群没有差异。
这些发现拓宽了我们对肠神经系统参与 PD 的机制的理解，并指出胃肠道系统可能是一个潜在的治疗靶点，尤其是在疾病的早期阶段。此外，我们的结果表明 T 细胞和 B 细胞在维持炎症以及最终影响α-突触核蛋白错误折叠和聚集方面发挥作用。
