A lymphatic waste-disposal system implicated in Alzheimer's disease

Abstract

The discovery that a set of lymphatic vessels interacts with blood vessels to remove toxic waste products from the brain has implications for cognition, aging and disorders such as Alzheimer’s disease.

Keywords: Ageing; Alzheimer's disease; Neuroscience.

Figure 1 |. Regulation of waste clearance in the brain.

a, The brain does not have its own lymphatic vessels. Proteins and waste are transported from brain interstitial fluid (ISF) along the walls of blood vessels to reach the cerebrospinal fluid (CSF) in the subarachnoid space within brain meninges. Tracers injected into the CSF can also diffuse back into the brain in the opposite direction (indicated by arrow). Da Masquita et al. report that lymphatic vessels, located in the brain meninges, drain CSF and ISF containing waste products. b, In a healthy mouse brain, lymphatic drainage of both fluids requires signalling between VEGF-C protein and its receptor VEGFR3, which is expressed in lymphatic endothelium. The protein amyloid-β (Aβ), which is associated with Alzheimer’s disease, is primarily removed by blood vessels. But during aging, both vessel systems can become dysfunctional. The diameter of the meningeal lymphatic vessels decreases, causing decreased waste clearance by this route. Decreased lymphatic drainage, along with impaired clearance by blood vessels, leads to amyloid-β accumulation in the brain.