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Historical reports suggest that they regulate brain volume by passively transporting cerebrospinal fluid (CSF) into dural venous sinuses. Here, we studied the microstructure of cerebral AG in humans with the aim of understanding their roles in physiology. We discovered marked variations in AG size, lobation, location, content, and degree of surface encapsulation. High-resolution microscopy shows that AG consist of outer capsule and inner stromal core regions. The fine and porous framework suggests uncharacterized functions of AG in mechanical CSF filtration. Moreover, internal cytokine and immune cell enrichment imply unexplored neuroimmune properties of these structures that localize to the brain\u2013meningeal lymphatic interface. Dramatic age-associated changes in AG structure are additionally identified. This study depicts for the first time microscopic networks of internal channels that communicate with perisinus spaces, suggesting that AG subserve important functions as transarachnoidal flow passageways. These data raise new theories regarding glymphatic\u2013lymphatic coupling and mechanisms of CSF antigen clearance, homeostasis, and diseases.<\/jats:p>","DOI":"10.1084\/jem.20220618","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:20:54Z","timestamp":1667960454000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":109,"title":["Arachnoid granulations are lymphatic conduits that communicate with bone marrow and dura-arachnoid stroma"],"prefix":"10.1084","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-2480","authenticated-orcid":true,"given":"Trishna","family":"Shah","sequence":"first","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2536-1665","authenticated-orcid":true,"given":"Sue E.","family":"Leurgans","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 1"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2532-7435","authenticated-orcid":true,"given":"Rashi I.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 3"},{"name":"Department of Neuroscience, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-3710","authenticated-orcid":true,"given":"Jingyun","family":"Yang","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 1"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-7339","authenticated-orcid":true,"given":"Chad A.","family":"Galloway","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Rochester Medical Center, Rochester, NY 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-1111","authenticated-orcid":true,"given":"Karen L.","family":"de Mesy Bentley","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Rochester Medical Center, Rochester, NY 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-1752","authenticated-orcid":true,"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 1"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 2"},{"name":"Department of Pathology, Rush University Medical Center, Chicago, IL 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4917-6907","authenticated-orcid":true,"given":"Rupal I.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Rush Alzheimer\u2019s Disease Center, Rush University Medical Center, Chicago, IL 1"},{"name":"Department of Pathology, Rush University Medical Center, Chicago, IL 6"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"2022120515054785200_bib1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29738","article-title":"Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI","volume":"6","author":"Absinta","year":"2017","journal-title":"Elife"},{"key":"2022120515054785200_bib2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41467-021-27887-0","article-title":"Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes","volume":"13","author":"Albayram","year":"2022","journal-title":"Nat. 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