Figure 3

The mature forms of cathepsin B and D decreased whereas Lamp1, Lamp2 and V0a1 proton pump subunit accumulated in PS1/APP mice hippocampus. (A-B) Western blots and quantitative analysis (n=5 for each age and animal group) of cathepsin B (A) and D (B) showed the existence of a significant decrease in the mature forms of both proteins. This decrease was observed exclusively in PS1/APP transgenic mice at both ages tested (6 and 18 months). C-D) Same mice model accumulated Lamp1 (tested by western blot, C, n=3) or Lamp2 (tested by immunohistochemistry at 6 and 18 months of age). Lamp2 immunolabeled sections of 6 (d1) and 18 (d2) month-old PS1/APP mice counterstained with Congo red for fibrillar amyloid plaques revealed Lamp2 labeling associated to dystrophic neurites surrounding amyloid plaques (arrows) at both ages that increased with age. In WT mice (d3 and d4, for 6 and 18 months respectively) Lamp-2 immunostaining was associated to cell somata and neuropile. No dystrophies were detected in control samples. E) Representative western blot and quantitative analysis (n=5 for each age and animal group) of V0a1 proton pump subunit in samples from 6 and 18 month-old WT and PS1/APP mice. Both, the mature and immature forms of V0a1 seemed to be accumulated, although not significantly, in 6 and 18 months of age PS1/APP mice. CA1, hippocampal subfield; DG, dentate gyrus; so, stratum oriens; sp, stratum pyramidale; sr, stratum radiatum. Scale bars: 500 μm (D), 25 μm (insets in d1 and d2).