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

Ding, Xue Bing ; Wang, Xin Xin ; Xia, Dan Hao ; Liu, Han ; Tian, Hai Yan ; Fu, Yu ; Chen, Yong Kang ; Qin, Chi ; Wang, Jiu Qi and Xiang, Zhi , et al. (2021) In Nature Medicine 27(3). p.411-418
Abstract

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 role1–5. 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... (More)

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 role1–5. 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.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
27
issue
3
pages
8 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85100094851
  • pmid:33462448
ISSN
1078-8956
DOI
10.1038/s41591-020-01198-1
language
English
LU publication?
yes
id
25d491a6-ebd0-4993-8466-ec17233c0ec4
date added to LUP
2022-01-13 12:43:23
date last changed
2024-06-17 02:33:24
@article{25d491a6-ebd0-4993-8466-ec17233c0ec4,
  abstract     = {{<p>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<sup>1–5</sup>. 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.</p>}},
  author       = {{Ding, Xue Bing and Wang, Xin Xin and Xia, Dan Hao and Liu, Han and Tian, Hai Yan and Fu, Yu and Chen, Yong Kang and Qin, Chi and Wang, Jiu Qi and Xiang, Zhi and Zhang, Zhong Xian and Cao, Qin Chen and Wang, Wei and Li, Jia Yi and Wu, Erxi and Tang, Bei Sha and Ma, Ming Ming and Teng, Jun Fang and Wang, Xue Jing}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{411--418}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease}},
  url          = {{http://dx.doi.org/10.1038/s41591-020-01198-1}},
  doi          = {{10.1038/s41591-020-01198-1}},
  volume       = {{27}},
  year         = {{2021}},
}