Toxicity of APP-C31 co-transfection was lost in APP deleted of Jcasp domain. (A) APPΔJ1 is a construct with a 13 amino acid deletion consisting of the entire Jcasp region while APPΔJ2 was a 9 amino acid deletion construct preserving the VEVD caspase cleavage motif. (B) Western blot using an end-specific antibody, APP-α664 (upper most). APPΔC31 and APP695ΔJ2_VEVD_ΔC31 transfected cells, but not wild type APP (APPwt) were immunoreactive to APP-α664 antibody. Following staurosporine treatment (STS), Asp-664 cleavage was detected in APP695wt transfected cells, but not in APP695ΔJ1, APP695ΔJ2 or APPD664A transfected cells. Expression of all constructs was comparable as determined by immunoblotting with 6E10 antibody. Cell death assay by ethidium homodimer staining (C) showed significantly increased cytotoxicity only for C31 cotransfected with APPwt. Neither Jcasp deleted constructs was able to augment C31 induced cytotoxicity (*p ≤ 0.001).