title: Growth-associated protein 43 in lesions and cerebrospinal fluid in multiple sclerosis.
abstract: Axonal damage in multiple sclerosis (MS) is correlated to disease progression. Early axonal damage may be compensated for by regenerative processes. Growth-associated protein 43 (GAP-43) is a marker for axonal growth and synaptogenesis in various neurodegenerative diseases. We investigated the expression of GAP-43 in 48 MS grey and white matter lesions of different stages. Decreased GAP-43 expression was found in 74% of the white matter lesions, independent of the lesion stage. In 19 out of 35 white matter lesions, areas of increased GAP-43 expression were present immediately adjacent to the lesions. Increased or unaltered expression was observed in remyelinated lesions. GAP-43 was expressed in neurofilament-positive structures. GAP-43 expression appeared unchanged in grey matter lesions. Macrophages were present in the areas of changed GAP-43 expression. cerebrospinal fluid GAP-43 levels were negatively correlated with magnetic resonance imaging measures of whole-brain atrophy (r = -0.30). In conclusion, these results indicate that decreased GAP-43 immunopositivity reflects axonal damage in MS lesions, which may again be reflected in decreased cerebrospinal fluid levels. The increased levels of GAP-43 in remyelinated or nondemyelinated white matter close to MS lesions may reflect regenerative attempts by damaged axons.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, the Netherlands. c.teunissen@vumc.nl
authors.forename: C E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: C D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: B
authors.initials: B
authors.lastname: Jasperse
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: H
authors.initials: H
authors.lastname: Vanderstichele
authors.forename: E
authors.initials: E
authors.lastname: Vanmechelen
authors.forename: C H
authors.initials: CH
authors.lastname: Polman
authors.forename: L
authors.initials: L
authors.lastname: Bö
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein