Fig. 1

Cystatin B (CSTB) abundance is increased and cathepsin B activity is reduced in the brains of individuals with AD-DS, independently of changed cathepsin B protein level or cathepsin D activity. Cystatin B (CSTB) (a–d) and cathepsin B (a, e, f Ab-3 or b, g ab92955), protein abundance measured by western blot in human temporal cortex from people who had AD-DS, EOAD and healthy ageing. c, d Type of case altered the abundance of CSTB protein (ANOVA β-actin F (2,18) = 9.087, p = 0.002; GAPDH F(2,21) = 7.500, p = 0.003). CSTB abundance was higher in individuals who had AD-DS than those with EOAD (pairwise comparisons with Bonferroni correction β-actin p = 0.008, GAPDH p = 0.020) and healthy controls from the general population (pairwise comparisons with Bonferroni correction, β-actin p = 0.024; GAPDH p = 0.013), with no difference in abundance between individuals with EOAD and control individuals (pairwise comparisons β-actin and GAPDH p = 1.000). e–g The abundance of mature cathepsin B protein, e, f Ab-3 or g ab92955, was not altered by the type of case (Ab-3 ANOVA β-actin F(2,16) = 3.051, p = 0.075; GAPDH F (2,21) = 2.141, p = 0.143) (ab92955 ANOVA F(2,18) = 0.970, p = 0.398). h Type of case affected cathepsin B activity (ANOVA F(2,22) = 9.027, p < 0.001); activity was significantly higher in individuals who had EOAD than in controls (pairwise comparisons with Bonferroni correction p = 0.004), but lower in individuals with AD-DS than those with EOAD (pairwise comparisons with Bonferroni correction, p = 0.012), with no difference between individuals with AD-DS and control individuals (pairwise comparisons p = 1.000). (i) Within case types, no significant correlations between age (in years) at time of death were observed (simple linear regression, Healthy ageing r² = 0.1962 p = 0.199, EOAD r² = 0.0989 p = 0.376 and AD-DS r² = 0.0079 p = 0.807). j Type of case significantly affected cathepsin D activity (ANOVA F(2,16) = 6.360, p = 0.009); activity was significantly lower in individuals who had EOAD than in healthy controls (pairwise comparisons with Bonferroni correction p = 0.022), no significant difference in activity was observed between AD-DS and healthy ageing controls (pairwise comparisons with Bonferroni correction, p = 0.180), with no difference between in individuals with AD-DS and those with EOAD (pairwise comparisons p = 1.000). Individual data points are technical means for independent biological samples, error bars SEM. *p < 0.05 and **p < 0.01