Study Rationale: Sterols, including cholesterol, are very abundant in the brain, where they form important components of cell membranes and act as signaling molecules within and between cells. Disruption of the sterol composition in brain cells is likely to result in neurological disorders such as Parkinson’s disease (PD). Such disruption can be measured by analyzing samples of blood plasma and the cerebrospinal fluid (CSF) that bathes the brain. Changes in sterol composition can therefore be used as a biomarker for assessing the risk, onset and progression of PD.
Hypothesis: Based on data from our earlier MJFF study, we hypothesize that two brain-derived sterol-acids found in CSF and another sterol made in nerve cells and found in blood plasma can serve as biomarkers for early PD. We also hypothesize that dysregulated sterol metabolism in brain is associated with PD progression.
Study Design: We will analyze both plasma and CSF samples collected from people with PD and from healthy volunteers using a technique called liquid chromatography-mass spectrometry (LC-MS). We have developed a methodology to enhance the sensitivity of sterol analysis by LC-MS. Our method allows us to determine the identity and amounts of multiple different sterols in plasma and CSF. These measurements will allow us to assess how a variety of sterols differ in quantity between people with and without PD and to evaluate how their quantities vary with the progression of disease.
Impact on Diagnosis/Treatment of Parkinson’s disease: The pattern of sterols found in plasma or CSF may provide a biomarker that will aid in the early diagnosis and treatment of PD. Our findings should also allow stratification of subjects for clinical trials. Measurements collected over time will allow clinicians to track disease and select the best treatments.
Next Steps for Development: If successful, we will discover a novel set of biomarkers that will aid diagnosis, track disease progression and inform best treatment. Such biomarkers can easily be incorporated into clinical assays.