Neuroscience: Cognitive decline in mice associated with lymphatic dysfunction

Dysfunction of the meningeal lymphatic vessels - a network of vessels located within the membranes that surround the central nervous system that drain macromolecules - may be an aggravating factor in Alzheimer’s disease pathology and age-associated cognitive decline. The results of this study in mice are published online in Nature this week.

Lymphatic vessels within the meninges have been discovered in rodents, non-human primates and humans. However, their function in the central nervous system and their role in pathologies of the central nervous system remains poorly understood.

Jonathan Kipnis and colleagues show that meningeal lymphatic vessels drain macromolecules from the cerebrospinal and interstitial fluid of the central nervous system into the cervical lymph nodes. The authors found that impairment of meningeal lymphatic function in young-adult mice resulted in learning and memory deficits. They note that in aged mice, there was significant disruption of meningeal lymphatic function, which may underlie some of the aspects of age-associated cognitive decline. Treatment of aged mice with vascular endothelial growth factor C enhanced meningeal lymphatic drainage and clearance of macromolecules from the cerebrospinal and interstitial fluid in the brain, resulting in improved learning and memory performance.

In transgenic mouse models of Alzheimer’s disease, disruption of meningeal lymphatic vessels promoted amyloid deposition in the meninges, which closely resembled human meningeal pathology. The authors suggest that augmentation of meningeal lymphatic function may be a promising therapeutic target for preventing or delaying age-associated neurological diseases.