Fig. 4: iPSc-derived neurons from LRRK2 G2019S PD patients and GBA1 PD patient show altered GCase activity compared to neurons derived from healthy subjects.

a Representative confocal images of iPSC-derived neurons stained with TH, DAT, and TUJ1 antibodies to verify proper differentiation to dopaminergic cells. b GCase activity measured in iPSC-derived neurons obtained from four healthy controls, one GBA1 L444P PD patients and two LRRK2 G2019S PD patients (2–3 replicates per individual). Data show that GBA1 PD patients have a reduced GCase activity compared with controls, while LRRK2 PD patients present increased GCase activity (data are expressed as mean ± SEM). c GCase activity measured in iPSC-derived dopaminergic neurons obtained from one healthy control in which the LRRK2 G2019S was introduced (Control #5 G2019S edited) show an increased enzymatic activity compared with the non-edited neuronal cells (Control #5). Similarly, GCase activity was reduced to a level similar to the Control #5 iPSC-derived neurons in LRRK2 G2019S dopaminergic cells (LRRK2-G2019S #2) upon gene correction (LRRK2-G2019S #2 GC). One-way ANOVA with Tukey’s post-test (**p < 0.01; ****p < 0.0001; data are expressed as mean ± SEM). d Efficiency of the differentiation into TH- positive neurons in LRRK2-G2019S #2 and LRRK2-G2019S #2 GC is about 30% of neurons (data are expressed as mean ± SEM). e Western blot showing pRAB10 and GCase levels in LRRK2-G2019S #2 and LRRK2-G2019S #2 GC. GCase level and pRAB10 were expressed as ratio of total RAB10 and β-actin, respectively.