Contrasting patterns of interleukin signalling in LRRK2 and idiopathic Parkinson's

Abstract

Sporadic PD and LRRK2-associated Parkinsons Disease (PD) present with similar features although the familial form of disease is classically associated with less cognitive impairment, better REM sleep behaviour, and reduced incidence of hyposmia but more freezing gait and postural instability. Although being classified as the same disease from a clinical perspective there is an ongoing debate on whether these 2 conditions are linked to different causative molecular mechanisms. In this work we analysed the transcriptomics and proteomics profile of sporadic and LRRK2 PD patients to contrast and compare inflammatory markers in blood and CSF. Analyses showed molecular differences in the burden of inflammatory signals clearly differentiating the sporadic and the familial forms of disease. Finally, a cluster of closely connected proteins whose expression levels were changed in the familial forms of disease was highlighted. The levels of these inflammatory markers were associated with tau pathology suggesting this protein cluster might be a system model to evaluate the control of tau metabolism in the presence of LRRK2 mutations.