title: Fibrosis of the Choroid Plexus Filtration Membrane.
abstract: We report a previously undescribed inflammatory lesion consisting of deposition of activated complement (C3d and C9neo) in association with major histocompatibility complex type II (MHC2)-positive activated microglia in choroid plexus villi exhibiting classical fibrous thickening of the pericapillary filtration membrane. The proportion of villi affected ranged from 5% to 90% in 56 adult subjects with diseases of the CNS and 11 subjects with no preexisting disease of the CNS. In 3 of the 4 children studied, 2% or less of examined villi showed stromal thickening, complement deposition, and the presence of MHC2-positive microglia; in adults, the proportion of villi affected increased with age. Other features of the lesion included loss of capillaries and failure by macrophages to clear extracellular particulate electron-dense material by clathrin-mediated phagocytosis. This choroid plexus lesion may relate pathogenetically to age-related macular degeneration and to Alzheimer disease, 2 other conditions with no known risk factors other than increasing age. All 3 conditions are characterized by the presence of damaged capillaries, inflammatory extracellular aggregates of mixed molecular composition and defective clearance of the deposits by macrophages.
authors.affiliation: From the The Institute of Clinical Neurosciences and the Nerve Research Foundation, Department of Medicine, University of Sydney, NSW, Australia (JWP, JDEP)Department of Neurology, Royal North Shore Hospital, St. Leonards, Sydney, NSW, Australia (JDEP)Electron Microscope Unit, Department of Anatomical Pathology, Concord Repatriation Hospital, Concord, Sydney, NSW, Australia (PDK) john.prineas@sydney.edu.au.
authors.forename: John W
authors.initials: JW
authors.lastname: Prineas
authors.affiliation: From the The Institute of Clinical Neurosciences and the Nerve Research Foundation, Department of Medicine, University of Sydney, NSW, Australia (JWP, JDEP)Department of Neurology, Royal North Shore Hospital, St. Leonards, Sydney, NSW, Australia (JDEP)Electron Microscope Unit, Department of Anatomical Pathology, Concord Repatriation Hospital, Concord, Sydney, NSW, Australia (PDK).
authors.forename: John D E
authors.initials: JD
authors.lastname: Parratt
authors.affiliation: From the The Institute of Clinical Neurosciences and the Nerve Research Foundation, Department of Medicine, University of Sydney, NSW, Australia (JWP, JDEP)Department of Neurology, Royal North Shore Hospital, St. Leonards, Sydney, NSW, Australia (JDEP)Electron Microscope Unit, Department of Anatomical Pathology, Concord Repatriation Hospital, Concord, Sydney, NSW, Australia (PDK).
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kirwan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002831:Choroid Plexus / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
keywords: Alzheimer disease; Choroid plexus; Complement; Macular degeneration; Multiple sclerosis.