title: Amyloid precursor protein (APP) expression in multiple sclerosis lesions.
abstract: The amyloid precursor protein (APP) is rapidly induced in reactive glial cells in response to several pathological stimuli including inflammation. In the present study, observations previously made in animal models of autoimmune central nervous system inflammation have been extended to the analysis of multiple sclerosis (MS) lesions. A total of thirty fresh-frozen tissue blocks from six histopathologically normal control and six MS cases have been examined immunocytochemically with monoclonal antibodies directed against either C- or N-terminal epitopes of APP. Histopathological evaluation of disease progression was based on hematoxylin-eosin and oil red O staining and immunocytochemistry for T cells, macrophages/microglia, astrocytes, and oligodendrocytes. In control cases, APP immunoreactivity was generally low and confined to blood vessel walls, oligodendrocytes in white, and neurons in grey matter. In actively demyelinating plaques, however, levels of APP immunoreactivity were high, localised on T lymphocytes, foamy macrophages, activated microglia, and reactive astrocytes including astrocytic processes. In more chronic lesions, levels of APP immunoreactivity were generally lower than in acute lesions, mainly found on reactive astrocytes, their processes and a few macrophages/microglia depending on the stage of plaque development. In addition, a few 14E-positive oligodendrocytes and, moreover, numerous axons exhibited APP immunoreactivity, which was particularly pronounced with anti-C-terminal antibodies. These results demonstrate that APP is induced on reactive glial cells but also on T lymphocytes during demyelination. The extent of APP expression appears to be correlated to histopathological lesion development and thus suggests that APP detection serves as a sensitive marker for disease progression in MS.
authors.affiliation: Department of Pathology, University Hospital, Zurich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Gehrmann
authors.forename: R B
authors.initials: RB
authors.lastname: Banati
authors.forename: M L
authors.initials: ML
authors.lastname: Cuzner
authors.forename: G W
authors.initials: GW
authors.lastname: Kreutzberg
authors.forename: J
authors.initials: J
authors.lastname: Newcombe
mesh_terms: D000328:Adult; D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D009836:Oligodendroglia / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal