An increase in the levels of alpha-synuclein -- a sticky protein that clumps in the brains of people with Parkinson's disease (PD) -- has been directly linked to an increased risk of Parkinson's. However, it remains unclear whether total alpha-synuclein levels in the cerebrospinal fluid or blood plasma can predict the onset or progression of PD or differentiate PD from other diseases related to alpha-synuclein. This is, in part, because the results of tests for alpha-synuclein vary greatly.
After alpha-synuclein is produced, the cell can make additional changes to the protein. These changes are known as post-translational modifications (PTMs). Existing tests for alpha-synuclein may be less effective because of PTMs, and for that reason, measurements of total alpha-synuclein levels in biosamples may be inaccurate.
In this study, we will use highly pure alpha-synuclein proteins as a standard to evaluate the effectiveness of four of the most commonly used total alpha-synuclein tests. We will assess whether these tests can detect different forms of naturally occurring alpha-synuclein, including those with PTMs.
Impact on Diagnosis/Treatment of Parkinson's Disease:
This study will explain inconsistencies in the results of alpha-synuclein testing in the human cerebrospinal fluid clarify the value of alpha-synuclein level as a potential diagnostic marker (objective measure) for PD.
Next Steps for Development:
Next, we will pursue the development of better tests capable of accurate measurement of total alpha-synuclein or the ratio of specific forms of alpha-synuclein to the total alpha-synuclein.