Loss of LRRK2 causes age-dependent bi-phasic alterations of α-synuclein. Representative Western blots show that while there is no significant difference in the levels of α-synuclein between LRRK2-/- mice and wild-type (+/+) controls at one month of age, high-molecular-weight (HMW) α-synuclein-immunoreactivity is significantly decreased in the RIPA buffer-insoluble fractions of LRRK2-/- kidneys at 7 months of age, suggesting increased degradation of α-synuclein. The level of HMW α-synuclein immunoreactivity is increased dramatically in the RIPA buffer-insoluble fractions of LRRK2-/- kidneys at 20 months of age, suggesting increased aggregation of α-synuclein. The specificity of the α-synuclein antibody had been confirmed previously using samples from α-synuclein-/- mice  and were confirmed again using samples from multiple independent lines of α-synuclein-overexpressing transgenic mice [14, 23]. ns, not significant; *, P < 0.05; **, P < 0.01.