Written by | Wang Cong
Parkinson's disease (PD), a complex neurodegenerative disease, is one of the most common degenerative diseases of the central nervous system, the main motor features include tremor, rigidity, bradykinesia and postural imbalance, etc.; non-motor features include constipation, rapid eye movement sleep behavior disorder and olfactory loss. The etiology and pathogenesis of Parkinson's disease are still not well understood, and it is believed that aging, genetics, and environmental factors (Environment) and their interactions are involved in the occurrence and development of Parkinson's disease.
Meningeal lymphatic vessels (mLV) are lymphatic networks that drain large molecules inside the central nervous system, and previous animal studies have shown that meningeal lymphatic vessel dysfunction is associated with the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, no direct evidence has been found in humans to support this relationship.
On January 18, 2021, Wang Xuejing, Teng Junfang of the First Affiliated Hospital of Zhengzhou University, and Ma Mingming of the People's Hospital Affiliated to Zhengzhou University, as co-corresponding authors, published a research paper entitled Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson's disease in the journal Nature Medicine, a top international medical journal.
The study found that meningeal lymphatic vessel (mLV) drainage dysfunction exacerbates α-syn pathology and promotes progression in idiopathic Parkinson's disease (iPD), suggesting that improving meningeal lymphatic drainage may be a promising therapeutic target for delaying or even preventing the progression of idiopathic Parkinson's disease (iPD).
Traditionally, the central nervous system (CNS) is an organ of immune privilege, mainly due to a lack of direct communication or contact with the surrounding immune system. However, the presence of lymphatic vessels (LV), or meningeal lymphatic vessels (mLV), has been confirmed in mice and humans.
Some recent animal studies support the possible involvement of meningeal lymphatic vessels (mLV) in neurodegenerative diseases and sequelae of post-traumatic brain injury. For example, in a mouse model of Alzheimer's disease, disruption of meningeal lymphatic vessels (mLV) increases β amyloid deposition in the meninges. In mouse models of Parkinson's disease, blocking meningeal lymphatic drainage is found to exacerbate Parkinson's disease-like pathology.
But so far, no direct evidence has been obtained from patients with neurodegenerative diseases to support these findings in animal models. A noninvasive dynamic approach to quantitative human meningal lymphatic drainage function is needed to understand the role of meningeal lymphatic vessels (mLV) in neurological disorders.
In this study, the research team used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymph fluid flow in patients with normal control and idiopathic Parkinson's disease (iPD) or atypical Parkinson's disease (AP).
The study found that patients with idiopathic Parkinson's disease (iPD) had significantly reduced flow of meningeal lymphatic vessels (mLVs) through the superior sagittal and sigmoid sinuses and had significantly delayed deep-neck lymph node perfusion compared to patients with atypical Parkinson's disease (AP). Patients with idiopathic Parkinson's disease (iPD) or atypical Parkinson's disease (AP) did not differ significantly in meningeal lymphatic vessel (mLV) size (cross-sectional area) from the control group.
α-synuclein (α-syn) is a soluble protein expressed presynaptically and perinuclear in the central nervous system.
Misfolding and deposition of α-synuclein (α-syn) is closely related to a variety of diseases such as Parkinson's disease, Lewy body dementia, multisystem atrophy, and simple autonomic failure. Prefabricated α-syn fibers can cause misfolding of endogenous α-synuclein (α-syn).
On February 18, 2020, Ding Xuejing et al. published a paper in the journal Nature Communications, successfully creating a mouse model of simple autonomic failure induced by prefabricated α-syn fiber injection for the first time.
Based on the above research model, the team found that in mice injected with prefabricated α-syn fibers, α-syn pathology followed delayed meningeal lymphatic drainage, loss of tight connections between meningeal lymphatic endothelial cells, and increased meningeal inflammation.
Finally, blocking blood flow through the meningeal lymphatic vessels (mLV) in mice treated with precast α-syn fibers increases α-syn pathological conditions and exacerbates motor and memory deficits.
These results suggest that meningeal lymphatic vessel (mLV) drainage dysfunction exacerbates α-syn pathology and promotes the progression of Parkinson's disease.
These results support the hypothesis that meningeal lymphatic vessels (mLV) play a role in maintaining metabolic balance in the central nervous system and that meningeal lymphatic vessel (mLV) dysfunction is involved in the pathogenesis of neurodegenerative lesions associated with protein aggregation.
Taken together, the study found that patients with idiopathic Parkinson's disease (iPD) had impaired meningeal lymphatic vessel function, while patients with non-typical Parkinson's disease (AP) found no significant changes. Meningeal lymphatic dysfunction has been shown to be particularly associated with the pathological process of idiopathic Parkinson's disease (iPD), so improving meningeal lymphatic drainage may be a promising therapeutic target for delaying or even preventing the progression of idiopathic Parkinson's disease (iPD).
Thesis Link:
https://www.nature.com/articles/s41591-020-01198-1
https://www.nature.com/articles/s41467-019-14189-9