Journal Article

Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease

Teng, Jun-Fang, Liu, Han, Qin, Chi, Wang, Wei, Fu, Yu, Zhang, Zhong-Xian, Cao, Qin-Chen, Wu, Erxi, Tian, Hai-Yan, Chen, Yong-Kang, Xiang, Zhi, Ma, Ming-Ming, Tang, Bei-Sha, Wang, Xin-Xin, Ding, Xue-Bing, Wang, Xue-Jing, Li, Jia-Yi, Xia, Dan-Hao, Wang, Jiu-Qi

2021

Overview

Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role 1 – 5 . In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD. Reduced meningeal lymphatic flow detected in patients with idiopathic Parkinson’s disease compared to patients with atypical Parkinsonian disorders and cognitively normal controls.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/308/53/2421 / 692/617/375/365/1718 / alpha-Synuclein - metabolism / Alzheimer's disease / Animal diseases / Basal ganglia / Basic Medicine / Biomedical and Life Sciences / Biomedicine / Cancer Research / Central nervous system diseases / Disease / Disease Progression / Disorders / Drainage / Endothelial cells / Fibrils / Humans / Infectious Diseases / Letter / Lymph nodes / Lymphatic drainage / Lymphatic system / Lymphatic Vessels - physiopathology / Magnetic Resonance Imaging / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / Meninges / Meninges - diagnostic imaging / Meninges - physiopathology / Metabolic Diseases / Molecular Medicine / Movement disorders / Neurodegenerative diseases / Neurosciences / Neurovetenskaper / Parkinson Disease - metabolism / Parkinson Disease - physiopathology / Parkinson Disease - therapy / Parkinson's disease / Pathogenesis / Pathology / Perfusion / Risk factors / Superior sagittal sinus / Synuclein / Tight junctions