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

Ding, Xiuhua; Wang, Xinxin; Xia, Danhao; Han, Lu; Tian, Haiyan; Fu, Yu; Chen, Yongkang; Qin, Chi; Wang, Jiu-Qi; Xiang, Zheng; Zhang, Zhongxian; Cao, Qian; Wang, Wei; Li, Jiayi; Wu, Erxi; Tang, Beisha; Ma, Mingming; Teng, Junfang; Wang, Xuejing

doi:10.1038/s41591-020-01198-1

Cited by 169 publications

(133 citation statements)

References 57 publications

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“…Different magnetic resonance imaging (MRI) protocols have been recently established to characterize the anatomy and function of meningeal LVs in humans. Some of these imaging techniques seem to allow the simultaneous measurement of CSF drainage into the CLNs, as well as the circulation of CSF/ISF solutes through the glymphatic pathway, under physiological and pathological conditions ( Absinta et al, 2017 ; Ringstad et al, 2017 ; Taoka et al, 2017 ; Eide et al, 2018 ; Zhou W. et al, 2020 ; Zhou Y. et al, 2020 ; Ringstad and Eide, 2020 ; Yang et al, 2020 ; Ding et al, 2021 ). Alongside MRI, optical coherence tomography (OCT) has also been used to image meningeal LVs in animal models ( Semyachkina-Glushkovskaya et al, 2017 ).…”

Section: Meningeal Lymphatic Drainage and Brain Physiology In Adulthood And Agingmentioning

confidence: 99%

“…Interestingly, A53T animals with ligated lymphatics also presented a decreased clearance of other macromolecules from the brain, namely of different toxic Tau species ( Zou et al, 2019 ). Impairing the drainage of brain fluids and molecules into the deep CLNs in a PD model of α-synuclein fibril’s toxicity (induced by injecting α-synuclein fibrils into the brain) resulted in a higher accumulation and propagation of phosphorylated α-synuclein in the brain ( Ding et al, 2021 ). Meningeal LVs have been recently implicated in the pathophysiology of human idiopathic PD.…”

Section: Role Of Meningeal Lymphatic (Dys)function In Neurological Disordersmentioning

confidence: 99%

“…Using an MRI technique to measure meningeal lymphatic parameters, the authors were able to show that patients with idiopathic PD exhibited significantly reduced flow through the meningeal LVs along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in the perfusion of deep CLNs by CSF-derived tracers, compared to atypical Parkinsonian patients. In fact, it was possible to accurately differentiate idiopathic PD and atypical Parkinsonian patients, with acceptable sensitivity and specificity, just by their profile of meningeal lymphatic outflow ( Ding et al, 2021 ). Even though idiopathic PD and multiple system atrophy (one type of atypical Parkinsonian disorder) are both α-synucleinopathies, they are characterized by different species of misfolded α-synuclein ( Shahnawaz et al, 2020 ), which highlights the need to understand whether the presence of distinct pathological α-synuclein aggregates in the CNS can have different effects on the meningeal lymphatic system.…”

Section: Role Of Meningeal Lymphatic (Dys)function In Neurological Disordersmentioning

confidence: 99%

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CNS-Draining Meningeal Lymphatic Vasculature: Roles, Conundrums and Future Challenges

2021

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A genuine and functional lymphatic vascular system is found in the meninges that sheath the central nervous system (CNS). This unexpected (re)discovery led to a reevaluation of CNS fluid and solute drainage mechanisms, neuroimmune interactions and the involvement of meningeal lymphatics in the initiation and progression of neurological disorders. In this manuscript, we provide an overview of the development, morphology and unique functional features of meningeal lymphatics. An outline of the different factors that affect meningeal lymphatic function, such as growth factor signaling and aging, and their impact on the continuous drainage of brain-derived molecules and meningeal immune cells into the cervical lymph nodes is also provided. We also highlight the most recent discoveries about the roles of the CNS-draining lymphatic vasculature in different pathologies that have a strong neuroinflammatory component, including brain trauma, tumors, and aging-associated neurodegenerative diseases like Alzheimer’s and Parkinson’s. Lastly, we provide a critical appraisal of the conundrums, challenges and exciting questions involving the meningeal lymphatic system that ought to be investigated in years to come.

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Section: Meningeal Lymphatic Drainage and Brain Physiology In Adulthood And Agingmentioning

confidence: 99%

Section: Role Of Meningeal Lymphatic (Dys)function In Neurological Disordersmentioning

confidence: 99%

Section: Role Of Meningeal Lymphatic (Dys)function In Neurological Disordersmentioning

confidence: 99%

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CNS-Draining Meningeal Lymphatic Vasculature: Roles, Conundrums and Future Challenges

2021

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“…The clearance of contrast agent in putative mLVs were also evaluated by the head high-resolution T2 fluid-attenuation inversion recovery (T2 flair) imaging discontinuously ( 24 ). We have recently assessed the mLVs-SSS flow in patients with idiopathic Parkinson’s disease or atypical Parkinsonian disorders using the dynamic contrast-enhanced MRI (DCE-MRI) ( 25 ), which may also be useful to measure abnormal mLVs flow in neuroinflammatory diseases. Here we used DCE-MRI to evaluate the mLVs-SSS flow quantitatively in NMOSD patients with acute attack (ANMOSD), NMOSD patients in chronic phase (CNMOSD), and normal control (NC).…”

Section: Introductionmentioning

confidence: 99%

Impaired Meningeal Lymphatic Flow in NMOSD Patients With Acute Attack

et al. 2021

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The meningeal lymphatic vessels (mLVs) in central nervous system (CNS) have been validated by rodent and human studies. The mLVs play a vital role in draining soluble molecules and trafficking lymphocytes, antigens and antibodies from CNS into cervical lymph nodes (CLNs). This indicates that mLVs may serve as a link between the CNS and peripheral immune system, perhaps involving in the neuroinflammatory disease. However, the morphology and drainage function of mLVs in patients with neuroinflammatory disease, such as neuromyelitis optica spectrum disorders (NMOSD), remains unexplored. Using the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we found that slower flow through mLVs along superior sagittal sinus in NMOSD patients with acute attack instead of NMOSD patients in chronic phase. The reduced flow in mLVs correlated with the disease severity evaluated by expanded disability status scale (EDSS). The receiver operating characteristic curve (ROC) indicated DCE-MRI might provide objective evidence to predict the acute relapse of NMOSD through evaluating the function of mLVs. Promoting or restoring the function of mLVs might be a new target for the treatment of NMOSD relapse.

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“…Ding and colleagues now provide compelling clinical data implicating meningeal lymphatic dysfunction in the pathogenesis of Parkinson's disease (PD) 4 . In the first of 3 experiments, using dynamic contrast‐enhanced magnetic resonance imaging, the authors found a significant reduction in the flow of meningeal lymphatic vessels in patients with PD compared with atypical parkinsonisms, with no intergroup difference in the cross‐sectional area of the vessels.…”

mentioning

confidence: 99%