Alpha-synuclein and Other Biomarkers in Biological Samples of LRRK2 Parkinsonís Disease
LRRK2 Cohort Consortium Resource Request, 2013
Cerebrospinal fluid (CSF) biomarkers of Alzheimerís pathology have been investigated in Parkinsonís 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 Parkinsonís disease.
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 Parkinsonís 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.
Chairman, Department of Neurology at Tel Aviv Sourasky Medical Center
Associate Professor of Neurology at Sackler School of Medicine, Tel-Aviv University
Location: Tel Aviv, Israel
Professor of Neurology and Director of the Parkinson Disease Research IDIBAPS at University of Barcelona, Spain
Senior Consultant in the Parkinson Disease and Movement Disorder Unit at Hospital Clinic Universitari de Barcelona
Location: Barcelona, Spain
Assistant Professor at Hebrew University
Location: Jerusalem, Israel