The involvement of APOE4 in Parkinson’s Disease

Background: Parkinson`s disease (PD) is the second most common neurodegenerative disease. The pathology usually includes the presence of Lewy bodies containing numerus proteins including α-synuclein aggregates and the death of dopaminergic neurons in the substantia nigra. 10% of PD cases are genetic and the rest are sporadic. Apolipoprotein E4 which is a major risk factor for Alzheimer`s disease, exhibit impaired autophagy and was suggested recently to be involved in PD. In the present study we examined the possible involvement of APOE4 in PD. Results: We have used immortalized human APOE3 and APOE4 targeted-replacement astrocytes cells to examine the uptake of α-synuclein and mutant pSer129 α-synuclein, and the expression of autophagy markers following α-synuclein treatment. We have also examined cell viability following MPP+ treatment. Treatment with MPP+ which is a common drug used to mimic PD symptoms, showed no significant differences in cell viability and in the levels of reactive oxygen species (ROS). In addition, our results indicate that the uptake of α-synuclein and mutant pSer129 α-synuclein by APOE4 expressing astrocytes was lower compared to APOE3 expressing astrocytes. Moreover, we measured the levels of autophagic marker p62/SQSTM1. Our results indicate that in the presence of α-synuclein, p62/SQSTM1 levels were increased in APOE3 but not in APOE4 expressing astrocytes. APOE4 expressing astrocytes exhibit high basal levels of p62 compared to APOE3 expressing cells. Conclusion: Taken together, our preliminary findings may indicate that APOE4 may be involved in Parkinson’s Disease.