REDUCTION IN AMYLOID-A AMYLOID FORMATION IN APOLIPOPROTEIN-E-DEFICIENT MICE

Apolipoproteins have been implicated in the formation of amyloid fibri ls, Recent studies have demonstrated that apolipoprotein E (apoE), alo ne or in combination with apolipoprotein J (apoJ), and other Lipoprote ins appear to enhance deposition of amyloid fibrils both in systemic a nd cerebral amyloids, especially Alzheimer's disease (AD), ApoE enhanc ed the ability of the amyloid beta-protein (1-40) fragment (A beta) to form fibrils in vitro, with apoE4 promoting the greatest fibril forma tion. ApoE was found associated with both human and mouse amyloid A (A A) deposits. To define the role of apoE in vivo, we utilized mice lack ing the apoE gene by gene targeting. We used the AA model in mice to c haracterize the function of the apoE protein in amyloid fibrillogenesi s, ApoE-deficient mice exhibited a decrease in deposition of AA when c ompared with heterozygous mutant or wild-type animals. In addition, ap oE-deficient mice that were injected with an adenovirus that expressed the human apoE3 gene had restored AA deposition and the apoE was asso ciated with the AA fibrils, These results are agreement with the in vi tro studies using the beta-peptide and suggest that apoE is not essent ial for amyloid fibrillogenesis but can promote the development of amy loid deposition.