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(SUPPLEMENT) Cataloguing Proteomic Differences in LRRK2-Associated Parkinsonism With and Without Evidence of Pathologic Neuronal Alpha-synuclein

Study Rationale: Alpha-synuclein is a protein found throughout the brain and body. In most people with Parkinson’s disease (PD), an accumulation of abnormal alpha-synuclein is thought to contribute to the death of dopamine-producing neurons. However, in 20 to 40% of people with parkinsonism caused by changes to the LRRK2 gene, abnormal alpha-synuclein is not detected. Understanding what leads to the loss of dopamine neurons and the features of parkinsonism in these individuals is critical to help develop treatments for their disease.

Hypothesis: We hypothesize that people with LRRK2-associated parkinsonism who have abnormal alpha-synuclein in their spinal fluid will show differences in additional proteins in their blood and spinal fluid compared to individuals who lack abnormal alpha-synuclein.

Study Design: We will measure overall protein expression in the blood and spinal fluid in individuals with LRRK2-associated parkinsonism and compare those who show evidence for abnormal alpha-synuclein to those who do not.

Impact on Diagnosis/Treatment of Parkinson’s disease: Understanding what leads to loss of dopamine neurons and the features of parkinsonism in individuals with parkinsonism without alpha-synuclein will be critical for developing treatments for their disease.

Next Steps for Development: This will be determined once study results are available.


  • Lana Chahine, MD, MS

    Pittsburgh, PA United States

  • Kristen A. Severson, PhD

    Cambridge, MA United States

  • Abby L. Olsen, MD, PhD

    Pittsburgh, PA United States

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