Study Rationale: Parkinson’s disease is usually diagnosed by symptoms, but the biological changes driving the disease begin many years earlier. While new tests that detect abnormal alpha-synuclein are important, they capture only one part of the disease. Parkinson’s also involves changes in the immune system, energy use in cells, nerve connections, and other pathways. Large-scale protein measurements in spinal fluid and blood can give a fuller picture of these changes. Early work shows that patterns of many proteins together may help identify different forms of Parkinson’s and related disorders. This project will build on those findings using several large research studies.
Hypothesis: We believe that groups of proteins measured in spinal fluid and blood can reveal the key biological processes driving Parkinson’s disease, distinguish Parkinson’s from related conditions, and predict who will decline more quickly.
Study Design: We will analyze thousands of proteins in spinal fluid and blood from people in major Parkinson’s research studies. Using advanced computer methods, we will search for patterns that separate Parkinson’s from healthy individuals and from related conditions such as dementia with Lewy bodies. We will also test whether these protein patterns can predict future changes in movement, thinking, and daily functioning. To ensure the results are reliable, we will repeat all analyses in independent groups of participants and across different protein-measurement technologies. This approach will show which biological pathways are most strongly linked to disease and which markers are consistent across studies.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this work could lead to simple blood or spinal fluid tests that diagnose Parkinson’s earlier, identify biological subtypes, and predict how the disease will progress. These tools could also help select the right patients for clinical trials and measure whether new treatments are working.
Next Steps for Development: The next steps would be to refine these biomarker panels for use in clinics and in clinical trials, confirm their value in larger and more diverse populations, and work with industry partners to develop tests that could be used broadly in healthcare settings.