title: Lipoprotein effects on Abeta accumulation and degradation by microglia in vitro.
abstract: An inflammatory response involving activated microglia in neuritic beta-amyloid plaques is found in Alzheimer's disease (AD) brain. Because HDL lipoproteins have been shown to carry the beta-amyloid peptide (Abeta) in plasma and CSF, we have investigated the influence of plasma high-density lipoprotein (HDL) and lipidated ApoE and ApoJ particles on the interaction of cultured rat microglia with Abeta1-42. Microglia degraded Abeta via a pathway sensitive to cytochalasin D and the scavenger receptor inhibitor, fucoidan. HDL increased the degradation of Abeta and the ratio of multimeric/monomeric Abeta in a dose-dependent manner. In contrast, lipidated ApoJ and ApoE decreased the degradation of Abeta, and the effects were ApoE isoform-dependent. Immuno-electron microscopy revealed internalized Abeta in endosomes and lysosomes as well as cell-associated Abeta in deep invaginations, which may be related to caveolae and surface-connected compartments. These data suggest that lipoprotein-dependent Abeta trafficking to microglia could be relevant to plaque pathogenesis in AD.
authors.affiliation: Sepulveda VAMC, GRECC, and Departments of Medicine and Neurology, University of California-Los Angeles, Sepulveda 91343, USA. gmcole@UCLA.edu
authors.forename: G M
authors.initials: GM
authors.lastname: Cole
authors.forename: W
authors.initials: W
authors.lastname: Beech
authors.forename: S A
authors.initials: SA
authors.lastname: Frautschy
authors.forename: J
authors.initials: J
authors.lastname: Sigel
authors.forename: C
authors.initials: C
authors.lastname: Glasgow
authors.forename: M D
authors.initials: MD
authors.lastname: Ard
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D008854:Microscopy, Electron; D058225:Plaque, Amyloid / Q000378:metabolism*; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D008074:Lipoproteins