The “Glymphatic-Lymphatic System Pathology” and a New Categorization of Neurodegenerative Disorders

Neurodegeneration is the ultimate manifestation of various neurodegenerative, neurovascular, and neuroinflammatory diseases, brain traumatisms, and aging. However, viewing neurodegeneration as the pathological/clinical epiphenomenon of numerous specific pathogenetic mechanisms has not provided a unitary neurodegenerative model nor a cure. It is emerging that neurodegeneration is related to failure of the glymphatic-lymphatic system(G-Ls) (Nedergaard and Goldman, 2020). This system represents a functionally integrated unit regulating solute trafficking and immune-surveillance in the CNS (Louveau et al., 2018; Nedergaard and Goldman, 2020). The G-Ls sub-serves CSF's flow from the subarachnoid spaces into the perivascular spaces and subsequently into the interstitium, and the aquaporin-4 water channels drive it. The cerebrospinal-interstitial fluid then passes to the venous perivascular and perineural spaces, lastly draining toxic molecules and immune cells from the brain into meninges and deep lymph nodes.