Influence of lipoproteins on microglial degradation of Alzheimer's amyloid beta-protein.
Amyloid beta-protein (Abeta), the major component of plaques in Alzheimer's disease, is a small hydrophobic protein that is carried on apolipoprotein E (ApoE)- and ApoJ-containing lipoprotein particles in plasma and cerebrospinal fluid (CSF). Microglia, the scavenger cells of the CNS, take up and degrade Abeta via lipoprotein receptors including scavenger receptors A and B, and possibly via other receptors. Lipoproteins, ApoE, and ApoJ influence the uptake and degradation of Abeta in vitro and in vivo. Differences in ApoE-E4, -E3, and -E2 isoforms with respect to Abeta binding to lipoproteins and delivery to cells, including microglia, may contribute to the increased risk of Alzheimer's disease for people with an APOE4 genotype and to risk reduction with APOE2.
Sepulveda VA Medical Center, Sepulveda, California 91343, USA. gmcole@ucla.edu
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D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism; D051152:Clusterin; D004705:Endocytosis; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D018832:Molecular Chaperones; D020033:Protein Isoforms / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D008074:Lipoproteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D018110:Receptors, Lipoprotein