The “Glymphatic-Lymphatic System Pathology” and a New Categorization of Neurodegenerative Disorders
Pasquale Gallina, Claudio Nicoletti, Antonio Scollato, Francesco Lolli
Abstract
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.