Aggregates of the protein alpha-synuclein, which accumulate in the brains of people with Parkinson’s disease (PD), can also be detected in biofluids like cerebrospinal fluid (CSF). Novel biochemical techniques can be used to “amplify” these samples, producing large amounts of the aggregates for detailed analyses. This project will amplify alpha-synuclein from the CSF of people with PD and analyze the structure and function of these aggregates. We will also assess whether the amplification process faithfully reproduces the appearance and behavior of the original aggregate sample. The ability to characterize the aggregates from individual patients would allow a more precise categorization of disease mechanism and thus pave the way for personalized medicine.
Parkinson’s disease is caused by the aggregation of specific forms of alpha-synuclein, and knowing which type of aggregate is responsible for an individual’s condition will allow more precisely tailored treatments.
Patient derived alpha-synuclein aggregates will be amplified by two independent methods and the resulting samples compared for their structure and function using advanced cell biological, biochemical and antibody-based techniques. We will also determine how faithful our amplification methods are, and work toward improving the techniques as needed.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
The process of copying aggregates from cerebrospinal fluid represents a recent leap in early diagnosis of Parkinson’s disease. This project holds the promise of advancing the technique to allow the examination of individuals’ specific disease processes, a key step toward personalized medicine.
Next Steps for Development:
Successful completion of this project will allow clinical studies to determine whether people with PD can be grouped based on their molecular alpha-synuclein pathology, supporting more tailored treatment strategies and improved prognoses.