Lipoprotein effects on aβ accumulation and degradation by microglia in vitro

✍ Scribed by Greg M. Cole; Walter Beech; Sally A. Frautschy; Jason Sigel; Connie Glasgow; March D. Ard

• Book ID: 102652357
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 537 KB
• Volume: 57
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19990815)57:4<504::aid-jnr10>3.0.co;2-h

✦ Synopsis

An inflammatory response involving activated microglia in neuritic ␤-amyloid plaques is found in Alzheimer's disease (AD) brain. Because HDL lipoproteins have been shown to carry the ␤-amyloid peptide (A␤) 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 A␤1-42. Microglia degraded A␤ via a pathway sensitive to cytochalasin D and the scavenger receptor inhibitor, fucoidan. HDL increased the degradation of A␤ and the ratio of multimeric/monomeric A␤ in a dose-dependent manner. In contrast, lipidated ApoJ and ApoE decreased the degradation of A␤, and the effects were ApoE isoform-dependent. Immuno-electron microscopy revealed internalized A␤ in endosomes and lysosomes as well as cell-associated A␤ in deep invaginations, which may be related to caveolae and surface-connected compartments. These data suggest that lipoproteindependent A␤ trafficking to microglia could be relevant to plaque pathogenesis in AD.