The goals of this study are 1. To compare the functional effects of the LRRK2 G2385R variant among carriers with and without Parkinson's disease (PD) and non-carriers with and without PD 2. To investigate the relationship between functional effects of the LRRK2 G2385R variant and PD associated phenotype 3. To investigate the biomarkers associated with PD conversion in the LRRK2 G2385R variant carriers 4. To compare the immune-related differences between PD patients/unaffected individuals with and without the LRRK2 G2385R mutation, and to investigate the effects of immune dysfunction on the clinical expression of PD
Description: Differences of blood LRRK2 activity measured by the optimized laboratory protocols among LRRK2 G2385R carriers and non-carriers with or without PD
Measure: LRRK2 activity Time: baselineDescription: Immune-related differences between LRRK2 G2385R carriers and non-carriers with or without PD. Immunological measures include (a) distribution of peripheral blood lymphocyte populations: flow cytometry analysis for surface staining of CD19, CD22, CD79A, PAX5 on B cells, and CD11b, CD14, CD16 on monocytes; (b) cytokine profiles in serum: IL-6, IFN-γ, TGF-β, TNF-α; (c) flow cytometry analysis for proteins involved in several LRRK2-related immune signaling pathways: TLR-4, IFN-γ and TGF-β, NF-κB.
Measure: Immune function Time: baselineDescription: Non-motor and motor symptoms are measured using the following methods: Brief Smell Identification Test (B-SIT) , Hamilton Depression Rating Scale (HAM-D) , RBD Questionnaire-Hong Kong (RBDQ-HK), Mini-Mental State Examination (MMSE), Non-Motor Symptoms Scale for Parkinson's Disease (NMSS), MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Purdue Pegboard
Measure: Clinical symptoms associated with blood LRRK2 activity Time: baselineCase-Control
There are 2 SNPs
While the LRRK2 G2019S mutation is the most common mutation present in Caucasians and certain ethic groups, the G2385R variant has been identified as a risk factor for sporadic PD in the Asian population (Chinese Han, Japanese and Korean). --- G2019S ---
In fact, in these populations, the occurrence of this mutation is thought to be higher than (up to 4% of PD patients) the occurrence of the G2019S mutation in the Caucasian population. --- G2019S ---
In contrast to G2019S, this variant has not been fully characterized. --- G2019S ---
Assessment of LRRK2 Activity in G2385R Carriers and Markers Predicting Conversion to and Progression of Parkinson's Disease. --- G2385R ---
LRRK2 Activity and Markers of Parkinson's Disease in G2385R Carriers The goals of this study are 1. --- G2385R ---
To compare the functional effects of the LRRK2 G2385R variant among carriers with and without Parkinson's disease (PD) and non-carriers with and without PD 2. To investigate the relationship between functional effects of the LRRK2 G2385R variant and PD associated phenotype 3. To investigate the biomarkers associated with PD conversion in the LRRK2 G2385R variant carriers 4. To compare the immune-related differences between PD patients/unaffected individuals with and without the LRRK2 G2385R mutation, and to investigate the effects of immune dysfunction on the clinical expression of PD LRRK2 activity. --- G2385R ---
To compare the functional effects of the LRRK2 G2385R variant among carriers with and without Parkinson's disease (PD) and non-carriers with and without PD 2. To investigate the relationship between functional effects of the LRRK2 G2385R variant and PD associated phenotype 3. To investigate the biomarkers associated with PD conversion in the LRRK2 G2385R variant carriers 4. To compare the immune-related differences between PD patients/unaffected individuals with and without the LRRK2 G2385R mutation, and to investigate the effects of immune dysfunction on the clinical expression of PD LRRK2 activity. --- G2385R --- --- G2385R ---
To compare the functional effects of the LRRK2 G2385R variant among carriers with and without Parkinson's disease (PD) and non-carriers with and without PD 2. To investigate the relationship between functional effects of the LRRK2 G2385R variant and PD associated phenotype 3. To investigate the biomarkers associated with PD conversion in the LRRK2 G2385R variant carriers 4. To compare the immune-related differences between PD patients/unaffected individuals with and without the LRRK2 G2385R mutation, and to investigate the effects of immune dysfunction on the clinical expression of PD LRRK2 activity. --- G2385R --- --- G2385R --- --- G2385R ---
To compare the functional effects of the LRRK2 G2385R variant among carriers with and without Parkinson's disease (PD) and non-carriers with and without PD 2. To investigate the relationship between functional effects of the LRRK2 G2385R variant and PD associated phenotype 3. To investigate the biomarkers associated with PD conversion in the LRRK2 G2385R variant carriers 4. To compare the immune-related differences between PD patients/unaffected individuals with and without the LRRK2 G2385R mutation, and to investigate the effects of immune dysfunction on the clinical expression of PD LRRK2 activity. --- G2385R --- --- G2385R --- --- G2385R --- --- G2385R ---
Differences of blood LRRK2 activity measured by the optimized laboratory protocols among LRRK2 G2385R carriers and non-carriers with or without PD. --- G2385R ---
Immune-related differences between LRRK2 G2385R carriers and non-carriers with or without PD. --- G2385R ---
While the LRRK2 G2019S mutation is the most common mutation present in Caucasians and certain ethic groups, the G2385R variant has been identified as a risk factor for sporadic PD in the Asian population (Chinese Han, Japanese and Korean). --- G2019S --- --- G2385R ---
A systematic biochemical characterization of the G2385R is necessary to determine if this cohort may be useful in LRRK2 kinase inhibitor trials. --- G2385R ---
This study will take advantage of the larger cohorts of LRRK2 G2385R variant carriers with or without PD established by the Chinese Parkinson Study Group in China. --- G2385R ---