Fight Aging!

It is becoming increasingly clear that issues in the drainage of cerebrospinal fluid from the brain play an important role in the onset of neurodegenerative conditions in late life. Neurodegenerative conditions are associated with a build up of various forms of molecular waste, such as toxic misfolded and otherwise altered proteins, in and around brain cells. It is likely that other stress signaling that provokes chronic inflammation in brain tissue is effectively amplified in effect as the drainage channels that normally carry metabolic products from the brain are reduced in capacity with age.

Leucadia Therapeutics has focused on the drainage path for the olfactory bulb, through the cribriform plate, in the development of Alzheimer's disease, which begins in this area of the brain specifically. The rest of the research community, meanwhile, is largely interested in the glymphatic system (including meningeal lymphatic vessels) in the context of cerebrospinal fluid drainage. Like the broader lymphatic system, the glymphatic system that drains the brain suffers a range of issues with age that reduce its capacity. Unlike the cribriform plate, there really isn't an obvious starting point for the development of ways to restore this drainage capacity. It seems likely that this is needed, however, and if achieved would significantly slow the degenerative aging of the brain.

Overview of the meningeal lymphatic vessels in aging and central nervous system disorders

The central nervous system (CNS) has been considered a relatively immune-privileged site. While the neuroimmune interactions play an important role in diverse neurological disorders, immune surveillance of the CNS remains unclear. The CNS contains microglia, but these cells are confined to the brain parenchyma and cannot interact with peripheral immune system under healthy conditions. Unlike the brain parenchyma, the meningeal lymphatic network enables immune surveillance of the brain efficiently. The discovery of meningeal lymphatic vessels (MLVs) in the CNS has shattered the traditional notion that the CNS is immune-privileged. Aging is accompanied by a functional decline of MLVs, which contribute to several age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), brain tumors, traumatic brain injury (TBI), multiple sclerosis (MS), and stroke.

Over the past few years, evidence for MLVs in the CNS has been accumulating. Recent studies revealed that some features of the meningeal lymphatic system are also present in humans. Defects in MLVs, which excrete metabolic wastes from the CNS to peripheral surroundings, are implicated in various neurological disorders. Although the contribution of MLVs in these diseases is not completely understood, the accumulation of metabolites, cellular debris, and misfolded proteins in the brain due to impaired drainage, which cannot be transported to deep cervical lymph nodes (dCLNs), may play key roles. It has been gradually recognized that the CNS relies on the function of MLVs to maintain homeostasis, and the draining function of MLVs also decreases with age.

However, for many CNS diseases, the causal relationship between MLVs and neuropathological changes is not fully clear. Here, after a brief historical retrospection, we review recent discoveries about the hallmarks of MLVs and their roles in the aging and CNS diseases, as well as potential therapeutic targets for the treatment of neurologic diseases.