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Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease

Authors :
Mesquita, Sandro
Louveau, Antoine
Vaccari, Andrea
Smirnov, Igor
Cornelison, R.
Kingsmore, Kathryn
Contarino, Christian
Onengut-Gumuscu, Suna
Farber, Emily
Raper, Daniel
Viar, Kenneth
Powell, Romie
Baker, Wendy
Dabhi, Nisha
Bai, Robin
Cao, Rui
Hu, Song
Rich, Stephen
Munson, Jennifer
Lopes, M.
Overall, Christopher
Acton, Scott
Kipnis, Jonathan
Source :
Nature; August 2018, Vol. 560 Issue: 7717 p185-191, 7p
Publication Year :
2018

Abstract

Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer’s disease promotes amyloid-β deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-β accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer’s disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases. Meningeal lymphatic dysfunction promotes amyloid-β deposition in the meninges and worsens brain amyloid-β pathology, acting as an aggravating factor in Alzheimer’s disease and in age-associated cognitive decline; improving meningeal lymphatic function could help to prevent or delay age-associated neurological diseases.

Details

Language :
English
ISSN :
00280836 and 14764687
Volume :
560
Issue :
7717
Database :
Supplemental Index
Journal :
Nature
Publication Type :
Periodical
Accession number :
ejs50664500
Full Text :
https://doi.org/10.1038/s41586-018-0368-8