Parkinson' disease is a progressive neurodegenerative disease arising from a collective effect of advancing age, genetic vulnerabilities and environmental toxins. The objective of the current study was to elucidate a synergistic effect of the advanced age, G2019S mutation and immunological stress (LPS) on neuroinflammation. In the present study, male mice were given five intraperitoneal injections of 250mg/kg of LPS (or saline) every alternate day across the two levels of the age and genotype (age; old vs young, genotype; WT vs G2019S). In line with our expectation, there was a significant loss of TH+ cells in old-G2019S mice that received LPS compared to the young-WT that received saline. There was a significant effect of age and genotype on baseline locomotor activity of these animals. Age and genotype predominantly affected other aspects like increased CX3CR1 expression and increased SiRT3 expression in SNc.