Background We and others have demonstrated marked abnormalities of mitochondrial and lysosomal function in peripheral tissue of patients with familial Parkinson’s disease (fPD).
Aim The aim of this project was to determine whether similar changes can also be detected in subgroups of patients with sporadic PD (sPD).
Methods Fibroblast cultures were established from 100 sPD patients and 50 age matched controls and assessed for mitochondrial membrane potential (MMP), intracellular ATP levels, mitochondrial morphology and number of lysosomes. Subsequent validation assays included mitochondrial complex assays, Western blot analysis for mitochondrial complex proteins, LAMP2 staining and cathepsin D/lysosomal activity.
Results 12/100 sPD patients had ATP levels 2 SD lower than the mean ATP of controls with an overall increase in mitochondrial area and count in the sPD cohort (p<0.05). The number and area of lysosomes was increased in sPD (p<0.05) with 15 sPD patients having a lysosome count >2 SD higher than the average of controls (>154%), but CathepsinD/lysosomal activity was decreased. Treatment with ursodeoxycholic acid (UDCA) improved mitochondrial function, but not lysosomal impairment in sPD patient tissue with combined impairment of mitochondrial and lysosomal function.
Conclusion The detection of distinct pathogenic mechanisms in individual patients with sPD may help for future disease-stratification.
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