Immune cells and their derived molecules have major impact on brain function. Our results demonstrate that meningeal space, surrounding the brain, is the site where CNS-associated immune activity takes place. We discovered a presence of meningeal lymphatic vessels that drain CNS molecules and immune cells to the deep cervical lymph nodes and also regulate perfusion of the brain by CSF (glymphatic flow). This communication between the CNS and meninges is playing a key role in several neurological, primarily in Alzheimer’s disease. Interestingly, the integrity of meningeal lymphatics also dictates the response to immunotherapy in AD. Meningeal lymphatics, overall, may serve as a novel therapeutic target for neurological disorders.