Loss of LRRK2 causes accumulation of lysosomal proteins and proteases at all ages examined. A. Representative Western blots show accumulated levels of lysosomal-associated membrane protein (LAMP-1) and active forms (cathepsins B (catB) and D (catD)) and proforms (cathepsin D (pro-catD)) of lysosomal proteases involved in the autophagy-lysosomal pathway in the kidneys of 1-, 7-, and 20-month-old LRRK2-/- mice. All the blots shown here were obtained using RIPA buffer-soluble fractions. Arrows indicate non-specific bands. The Western blots of Rab7 are used as loading control. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001. B. Immunohistochemical analysis revealed increased immunoreactivity of cathepsin B in the LRRK2-/- kidney at 20 months of age, which is associated with or clustered at granular structures. All scale bars: 20 μm.