title: Modest amyloid deposition is associated with iron dysregulation, microglial activation, and oxidative stress.
abstract: There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from AβPP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid-β-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-β-containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology.
authors.affiliation: Department of Physiology, Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. jjg@caltech.edu
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Gallagher
authors.forename: Mary E
authors.initials: ME
authors.lastname: Finnegan
authors.forename: Belinda
authors.initials: B
authors.lastname: Grehan
authors.forename: Jon
authors.initials: J
authors.lastname: Dobson
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Collingwood
authors.forename: Marina A
authors.initials: MA
authors.lastname: Lynch
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D007501:Iron