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closeReproducibility
Posted by Ashley_Bush on 15 Aug 2012 at 06:03 GMT
As the team responsible for Duce et al. 2010, Cell 142: 857, we are puzzled by these published findings.
We have reproduced the ferroxidase activity of APP in the transferrin assay using both in-house purified APP, as well as a recombinant full length APP-Fc fusion construct that is commercially available (http://www.creativebiomar...).
Concerning the assertion that we were measuring auto-oxidation, in our original publication, Duce et al. 2010, Cell 142: 857, we blanked our transferrin loading absorbance values on background auto-oxidation of iron in the absence of enzyme. In doing so we followed the published protocols of Bakker & Boyer 1986, J. Biol. CHem., 261: 13182, as we stated.
We plan to publish this further validation and optimization of the APP ferroxidase activity in a peer reviewed journal as soon as practicable. We will make a point of providing the background oxidation curves to show that this reaction is relatively minor compared to the APP-catalyzed iron oxidation, which resembles ceruloplasmin. We note that this may also be a suitable subject for the new PLOS ONE Reproducibility Initiative.
RE: Reproducibility
KouroshHE replied to Ashley_Bush on 15 Aug 2012 at 07:52 GMT
As the first author on this work, we are puzzled by all the inconsistencies that we have observed in the work that is done by Duce et al. Cell 142: 857 (2010). These inconsistencies together with our results suggest that the proposed ferroxidase activity of APP should be re-evaluated by the Alzheimer's community.