Meningeal lymphatics in aging and Alzheimer’s disease
| Autor: | Rajnish S. Dave, Russell J. Jaffe, Siddappa N. Byrareddy |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Amyloid β business.industry Dura mater General Medicine Disease Immune surveillance Article 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Cerebrospinal fluid Lymphatic system Deep cervical lymph nodes medicine business 030217 neurology & neurosurgery |
| Zdroj: | Nature |
| ISSN: | 2305-5847 2305-5839 |
| Popis: | Aging is a major risk factor for many neurological pathologies and the mechanisms underlying brain aging remain elusive. Unlike other tissues, the central nervous system (CNS) parenchyma is devoid of lymphatic vasculature and removal of waste products is performed mainly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels prompted for an assessment of their role in CNS waste clearance. Here we show that meningeal lymphatics are draining macromolecules from the CNS (CSF and ISF) into the cervical lymph nodes. Impairment of meningeal lymphatic function slows paravascular influx of CSF macromolecules and efflux of ISF macromolecules, and induces cognitive impairment. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of CSF macromolecules, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer’s disease (AD) promotes amyloid deposition in the meninges, which closely resembles human meningeal pathology, and aggravates parenchymal amyloid accumulation. Our findings suggest that meningeal lymphatic dysfunction may be an aggravating factor in AD 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. |
| Databáze: | OpenAIRE |
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