title: Oxidation of Abeta and plaque biogenesis in Alzheimer's disease and Down syndrome.
abstract: The processes involved with beta-amyloid (Abeta) degradation and clearance in human brain are not well understood. We hypothesized that the distribution of oxidatively modified Abeta, as determined by an affinity-purified antibody in the entorhinal and frontal cortices of Alzheimer's disease (AD), Down syndrome (DS), nondemented elderly control cases, and canine brain, would provide insight into the mechanisms of Abeta accumulation. Based upon plaque counts, oxidized Abeta was present within 46-48% of diffuse and primitive plaques and 98% of cored plaques. Dense punctate deposits of oxidized Abeta were distributed throughout the neuropil in AD and DS brains but were also present within controls with mild neuropathology and isolated cognitive impairments. Confocal studies indicate that punctate oxidized Abeta deposits were within activated microglia. Oxidatively modified Abeta may reflect the efforts of microglial cells to take up and degrade Abeta. Oxidative modification of Abeta may be an early event in Abeta pathogenesis and may be important for plaque biogenesis.
authors.affiliation: Institute for Brain Aging & Dementia, University of California, Irvine, California, 92697-4540, USA.
authors.forename: E
authors.initials: E
authors.lastname: Head
authors.forename: W
authors.initials: W
authors.lastname: Garzon-Rodriguez
authors.forename: J K
authors.initials: JK
authors.lastname: Johnson
authors.forename: I T
authors.initials: IT
authors.lastname: Lott
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
authors.forename: C
authors.initials: C
authors.lastname: Glabe
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D017628:Microglia / Q000737:chemistry / Q000473:pathology; D018613:Microscopy, Confocal; D010084:Oxidation-Reduction; D058225:Plaque, Amyloid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D006684:HLA-DR Antigens