In this report the authors show reproduction attempts on the reported function of GSAP on gama-secretase activity, particularly the processing of APP that leads to production of Aβ, a process that is important target of Alzheimer's disease. Two findings in the He et al 2010 paper were tested, first the 16kD cleavage (fig1c in He et al), second the specificity of GSAP in regulating gama- but not other secretase activity (e.g., beta, figS6 in He et al). The results directly contradict He et al result: 1. no 16kD protein (a C-term fragment) detected; 2. sAPPβ shows similar reduction when GSAP is reduced, therefore GSAP action is not restricted to gama-secretase. The authors do confirm He et al's result that GSAP knockdown reduces production of Aβ.
The experiments are well done and results clearly presented. While the methods and reagents used are slightly different than those of He et al 2010, the negative results are valid and consistent with Hussain et al which also challenged He et al. This report is suitable for Matters.
A few suggestions:
1. could the authors speculate why 16KD protein was not detected here or why He et al detected one with different methods? Could it be a cleavage product that does not contain the C-terminal end (thus not including the HA tag)?
2. is the cleavage prediction program the authors use accurate or robust? the prediction argument seems unnecessary given the provided experimental evidence.