Decreased cholesterol in olfactory mucosa-derived cells from Parkinson’s disease patients with leucine-rich repeat kinase 2 mutations

Objective: To investigate the changes in (1) the cholesterol level and (2) the activity and amount of the rate-limiting cholesterol biosynthetic enzyme, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoA-R), in olfactory mucosal cells biopsied from idiopathic Parkinson’s disease (iPD) patients and Parkison’s disease (PD) patients with leucine-rich repeat kinase 2 (LRRK2) mutations.

Background: We have previously reported that neuromelanin associated cholesterol is reduced in the substantia nigra in PD. Further, cholesterol biosynthesis is reported to be reduced in fibroblasts from patients with PD. Together these data suggest a change in cholesterol homeostasis in PD.

Methods: Olfactory mucosal cells were biopsied and cultured from six cases of iPD patients, four PD patients with LRRK2 mutations(two: A1442P and two G2019S mutations) and ten normal controls. Cellular cholesterol levels were measured by reverse phase high performance liquid chromatography and the activity and amount of HMG CoA-R were measured by metabolic radiolabelling andWestern blotting, respectively.