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Lipoprotein effects on aβ accumulation and degradation by microglia in vitro
Author(s) -
Cole Greg M.,
Beech Walter,
Frautschy Sally A.,
Sigel Jason,
Glasgow Connie,
Ard March D.
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990815)57:4<504::aid-jnr10>3.0.co;2-h
Subject(s) - microglia , scavenger receptor , apolipoprotein e , microbiology and biotechnology , lipoprotein , lrp1 , chemistry , caveolae , endosome , receptor , in vitro , pathogenesis , biochemistry , biophysics , cholesterol , biology , inflammation , ldl receptor , cell , medicine , immunology , disease
An inflammatory response involving activated microglia in neuritic β‐amyloid plaques is found in Alzheimer's disease (AD) brain. Because HDL lipoproteins have been shown to carry the β‐amyloid peptide (Aβ) 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 Aβ1–42. Microglia degraded Aβ via a pathway sensitive to cytochalasin D and the scavenger receptor inhibitor, fucoidan. HDL increased the degradation of Aβ and the ratio of multimeric/monomeric Aβ in a dose‐dependent manner. In contrast, lipidated ApoJ and ApoE decreased the degradation of Aβ, and the effects were ApoE isoform‐dependent. Immuno‐electron microscopy revealed internalized Aβ in endosomes and lysosomes as well as cell‐associated Aβ in deep invaginations, which may be related to caveolae and surface‐connected compartments. These data suggest that lipoprotein‐dependent Aβ trafficking to microglia could be relevant to plaque pathogenesis in AD. J. Neurosci. Res. 57:504–520, 1999. © 1999 Wiley‐Liss, Inc.