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ApoE Knockouts Unaffected in APP Expression and Processing

by June Kinoshita

11 November 1998 The critical role of ApoE in beta amyloid deposition was demonstrated last year by Eli Lilly scientists, who crossbred APP/PS1 transgenics with an ApoE knockout and found that these mice do not develop thioflavin S-positive deposits of fibrillar A-beta. In a series of follow-up studies (abstract 592.5), Kelly Bales and colleagues examined older mice, up to 22 months of age, and found that these animals continue to remain free of fibrillar A-beta. Additional studies showed that the ApoE knockouts did not differ from ApoE-positive mice in their levels of APP expression or processing of APP. Although these data suggest that ApoE plays a direct role in facilitiating A-beta deposition, Bales cautioned that "gene rescue experiments using the three human isoforms of ApoE will be required to confirm this hypothesis.