Table 1. Changes in protein secretion and shedding upon BACE1 inhibitor C3 treatment.

^aIPI accession number of the protein.

^bMean ratio between BACE1 inhibitor treatment (C3) and control (DMSO) conditions of the summed unique peptides intensities identified for a unique protein group for five biological replicates (C3/DMSO) shows remaining ectodomain levels upon BACE1 inhibition. SPECS values for remaining shedding of APP (0.67=67%), APLP1 (0.11=11%) and APLP2 (0.42=42%) correspond well to the literature. In neurons, APLP1 is mainly cleaved by BACE1 (Sala Frigerio et al, 2010), whereas APLP2 shedding is mediated to about 60% by BACE1 (Hogl et al, 2011). In contrast, total APP shedding was only mildly inhibited with C3, because it is known that inhibition of BACE1 cleavage of APP is accompanied by an increase in the ADAM10-mediated cleavage, resulting in only a moderate inhibition of total APP shedding upon BACE1 inhibition (Vassar et al, 1999; May et al, 2011).

^cStandard error of the mean for five biological replicates.

^dVariance score was calculated for all proteins. Proteins with a variance score of ≤0.35 were considered as proteins with a consistent change under BACE1 inhibition.

^eNumber of identified peptides of the protein group.

^fProtein type: Secreted: Secreted, soluble protein, Type I: type I membrane protein, Type II: type II membrane protein, Polytopic: membrane protein with multiple transmembrane domains, GPI: GPI-anchored membrane protein.