Apoptosis of peripheral blood lymphocytes in patients with LRRK2-associated Parkinson’s disease

Abstract

Mutations in the Leucine Reach Repeat Kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). Although the precise physiological and pathological role of LRRK2 is unclear, a direct link between mutant LRRK2 and apoptosis has been suggested. Using flow cytometric analysis (PI+Annexin V(FITC)) we showed increased spontaneous apoptosis of peripheral blood lymphocytes in patients with LRRK.2-associated PD compared to controls after 24 (P < 0.016) and 48 (P < 0.031 ) h of incubation (5 % CO2, 37 degrees C). We found the increased FAS mRNA level in peripheral blood lymphocytes of patients with LRRK2-associated PD compared to controls (P < 0.05) and to sporadic PD (sPD) (P < 0.002). Significant difference in FAS expression between patients with LRRK2-associated PD and controls remained after three years and was detected after 1 and 24 h during lymphocyte incubation (P < 0.03 and 0.05, respectively). Increased spontaneous lymphocytes apoptosis along to increased FAS expression in patients with LRRK2-associated PD suggest that LRRK2 mutations may lead to the activation of extrinsic apoptotic way.