FIGURE 6.

Schematics for LB formation in patients with mutations in GBA or LRRK2. The majority of GBA mutation carriers display a reduction in GCase enzyme activity in the absence of PD. PD manifestation in GBA mutation carriers requires additional environmental, age-related or genetic (possibly other LSD gene variants) triggers, which is accompanied by α-synuclein aggregation/LB formation. Pathogenic LRRK2 mutation carriers display deficits in lysosomal functioning due to deficits in proper endolysosomal trafficking, which is also associated with a decrease in GCase enzyme activity. Deficits in lysosomal functioning cause PD in the absence of LB formation. The presence of LBs in LRRK2-PD patients requires additional environmental, age-related or genetic (possibly other LSD gene variants) triggers.