Reduction in amyloid A amyloid formation in apolipoprotein-E-deficient mice.
Apolipoproteins have been implicated in the formation of amyloid fibrils. Recent studies have demonstrated that apolipoprotein E (apoE), alone or in combination with apolipoprotein J (apoJ), and other lipoproteins appear to enhance deposition of amyloid fibrils both in systemic and cerebral amyloids, especially Alzheimer's disease (AD). ApoE enhanced the ability of the amyloid beta-protein (1-40) fragment (A beta) to form fibrils in vitro, with apoE4 promoting the greatest fibril formation. ApoE was found associated with both human and mouse amyloid A (AA) deposits. To define the role of apoE in vivo, we utilized mice lacking the apoE gene by gene targeting. We used the AA model in mice to characterize the function of the apoE protein in amyloid fibrillogenesis. ApoE-deficient mice exhibited a decrease in deposition of AA when compared with heterozygous mutant or wild-type animals. In addition, apoE-deficient mice that were injected with an adenovirus that expressed the human apoE3 gene had restored AA deposition and the apoE was associated with the AA fibrils. These results are agreement with the in vitro studies using the beta-peptide and suggest that apoE is not essential for amyloid fibrillogenesis but can promote the development of amyloid deposition.
Kindy
M S
MS
Department of Biochemistry, University of Kentucky School of Medicine, and the Veterans Affairs Medical Center, Lexington 40536-0084, USA. mskindy@pop.uky.edu
Rader
D J
DJ
D000209:Acute-Phase Proteins / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000686:Amyloidosis / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D015139:Blotting, Southern; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009696:Nucleic Acids / Q000737:chemistry; D016133:Polymerase Chain Reaction; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D012835:Silver Nitrate / Q000008:administration & dosage; D013154:Spleen / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000209:Acute-Phase Proteins; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D006023:Glycoproteins; D009696:Nucleic Acids; D000685:Serum Amyloid A Protein; D014280:Triglycerides; C046748:amyloid enhancing factor; D012835:Silver Nitrate