Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Sandro Da Mesquita,Antoine Louveau,Andrea Vaccari,Igor Smirnov,R. Chase Cornelison,Kathryn M. Kingsmore,Christian Contarino,Christian Contarino,Suna Onengut-Gumuscu,Emily Farber,Daniel M.S. Raper,Daniel M.S. Raper,Kenneth E. Viar,Romie D. Powell,Wendy Baker,Nisha Dabhi,Robin Bai,Rui Cao,Song Hu,Stephen S. Rich,Jennifer M. Munson,Jennifer M. Munson,M. Beatriz S. Lopes,Christopher C. Overall,Scott T. Acton,Jonathan Kipnis +25 more
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TLDR
It is shown that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice and improves brain perfusion and learning and memory performance.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.read more
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Alzheimer Disease: An Update on Pathobiology and Treatment Strategies.
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CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.
Antoine Louveau,Jasmin Herz,Maria Nordheim Alme,Andrea Francesca Salvador,Michael Q. Dong,Kenneth E. Viar,S. Grace Herod,James Knopp,Joshua C. Setliff,Alexander L. Lupi,Sandro Da Mesquita,Elizabeth L. Frost,Alban Gaultier,Tajie H. Harris,Rui Cao,Song Hu,John R. Lukens,Igor Smirnov,Christopher C. Overall,Guillermo Oliver,Jonathan Kipnis +20 more
TL;DR: It is demonstrated that meningeal lymphatics drain CSF-derived macromolecules and immune cells and play a key role in regulating neuroinflammation and may represent a new therapeutic target for multiple sclerosis.
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Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid
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TL;DR: The importance of meningeal lymphatic vessels in the basal part of the skull for CSF clearance is revealed by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF.
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