Fig. 1

Analysis of Aβ accumulation in CatD-deficient hAPP transgenic mice. (A, B) Relative levels of insoluble (A) and soluble (B) Aβ40 (left) and Aβ42 (right) in 3-week-old hAPP transgenic mice with two (WT+), one (HET+), or no (KO+) functional copies of CTSD determined by ELISA specific for human Aβ. Note the prominent increases in insoluble Aβ levels in KO+ animals relative to both WT+ and HET+ controls. Data are mean ± SEM of 6 mice per genotype. (C) Representative images of pan-Aβ immunoreactivity in WT+ (left) and KO+ (right) brain. Note the prominent accumulation of Aβ in KO+ mice, which occurs exclusively intracellularly (arrowheads), in the absence of extracellular deposits. Scale bars represent 50 μm for the main images and 20 μm for the insets. (D, E) Relative levels of insoluble (D) and soluble (E) Aβ40 (left) and Aβ42 (right) in 6- to 10-month-old hAPP transgenic mice with two (WT+) or one (HET+) functional copies of CTSD determined by ELISA. No significant differences are evident between genotypes. Data are mean ± SEM of 6–8 mice per group. (F) Representative images of Aβ plaques in WT+ (left) and HET+ (right) cortex. Note the lack of differences in plaque size, number, or morphology, as confirmed by morphometric quantification (Sup Fig. 1A-C). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns = not significant