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Alpha-synuclein and Other Biomarkers in Biological Samples of LRRK2 Parkinson’s Disease

Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s pathology have been investigated in Parkinson’s disease (PD), and abnormal CSF protein levels (tau and phosphorylated tau, beta‐amyloid) have been described in patients with idiopathic PD (no known cause) that correlate with cognitive disturbances. To date information available on CSF levels of these potentially pathogenic proteins in both symptomatic and asymptomatic people who carry a mutation in the LRRK2 gene remains preliminary. Mutations in LRRK2 are the greatest known genetic contributor to Parkinson’s disease.

Project Description:
The primary objectives of our project are:

  • To measure the levels of alpha-synuclein, amyloid beta, tau protein and the phosphorylated version of tau protein in CSF from LRRK2 mutation carriers and to correlate them with the clinical features.
  • To measure the circulating cell-free mitochondrial DNA in CSF from LRRK2 mutation carriers.
  • To utilize a novel method to detect alpha-synuclein in CSF. It will be performed in two steps: first, validate the method in a cohort of idiopathic PD patients and controls and, second, determine alpha-synuclein levels in CSF from LRRK2 mutation carriers and controls from the LRRK2 Cohort Consortium.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The study of CSF proteins in LRRK2 mutation carriers could contribute to a better understanding of the pathogenesis of LRRK2 PD, could allow for detection of possible at-risk populations before the onset of motor symptoms, and could lead to the identification of progression biomarkers in LRRK2 PD subjects.


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