Objective/Rationale:
Patients with Parkinson’s disease (PD) are at a 5.9 times greater risk of developing dementia than the normal population. The identification of sensitive molecular and cellular biomarkers for the cognitive decline in PD patients will facilitate the earlier and more accurate diagnosis of cognitive impairment, identifying disease mechanisms, and novel targets for therapies. The goal of this project is to identify proteins in blood that might be used to predict dementia development in PD patients.
Project Description:
We will conduct two assays that survey over one hundred selected proteins in blood samples collected from a total of 100 participants, including 20 demented PD patients, 40 non-demented PD patients, and 40 normal control subjects. These assays measure precisely the amounts of selected proteins in blood samples. The results will be statistically analyzed to determine if the amounts of individual proteins differ between disease groups or between disease groups and normal control subjects. They will also measure the ability of an individual protein or a combination of measured proteins to better distinguish clinically non-demented from demented PD patients, or from normal control patients. Throughout the course of this study, we expect to identify candidate proteins that have the potential to predict dementia development in PD patients.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Currently there is no way to predict when and who will develop dementia in patients diagnosed with PD. If protein biomarkers in the blood are available for prediction or earlier diagnosis, it could then lead to development of drugs for prevention of dementia. The biomarker candidates identified in this study will lay the foundation for achieving these goals.
Anticipated Outcome:
We expect that a panel of proteins in the blood will be selected as biomarker candidates for distinguishing demented PD patients from non-demented PD patients. These results will be published so that other research groups can validate our findings. From this study, we will also confirm the concept that the pathophysiological changes associated with cognitive decline in PD patients could be reflected in biochemical changes in blood circulation. This could open up new directions for PD research.
Final Outcome
We have completed the project that had the objectives to identify inflammatory markers for Parkinson’s disease with dementia. The protein that showed the statistical differences between Parkinson’s without dementia and with dementia is called MIG (monokine induced by gamma interferon). This protein has been shown elevated in the plasma samples of patients with Alzheimer’s dementia before. Overall, our study showed convincingly that assay design and development should be a priority in order to have breakthrough in the blood biomarker discovery.