Research David Crosiers

Abstract

Parkinson's disease, Lewy Body dementia and Multiple System Atrophy are classified as alpha-synucleinopathies, sharing alpha-synuclein aggregation as their underlying pathology. Sleep disturbances, particularly REM-sleep behavior disorder (RBD), manifest early in alpha-synucleinopathies, preceding motor and cognitive symptoms. RBD, characterized by REM sleep without atonia (RSWA) and dream-enacting behavior, is the most specific prodromal stage of alpha-synucleinopathies. RBD occur years before the onset of motor and/or cognitive symptoms and formal diagnosis. Isolated RSWA without RBD indicates an even earlier stage. Differentiating iRSWA patients at risk of alpha-synucleinopathies from other causes is crucial for accurate and early diagnosis. In this research project we will assess biomarkers for neurodegeneration in individuals with iRSWA as early manifestations of alpha-synucleinopathies, with a primary focus on Parkinson's disease. These biomarkers include [123I-MIBG] myocardial scintigraphy, olfactory function and alpha-synuclein levels in blood. Additionally, we will investigate whether these biomarkers can distinguish different alpha-synucleinopathies, allowing for a more precise prediction of whether an individual with iRSWA is more likely to develop PD, DLB or MSA. This diagnostic approach facilitates early specialist referral for prodromal screening, enabling early diagnosis, patient stratification for disease-modifying treatments, intervention and follow-up care, and potential inclusion in neuroprotective clinical trials.

Researcher(s)

• Promoter: Crosiers David
• Co-promoter: Verbraecken Johan
• Fellow: Colman Kaat

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative brain disorder. Five causal genes (SNCA, LRRK2, PARK2, PINK1 and DJ1) leading to familial PD have already been identified. Variations in these genes have also been shown to increase susceptibility for sporadic PD. In my project, I am prospectively recruiting a population of familial and sporadic PD patients. Detailed phenotypic characterization of the patients is performed with standardized clinical scales at different time intervals. Genetic variations (simple and complex mutations) in the known causal genes will be identified and genotype-phenotype correlations will be established. Since disease progression is an important part of the phenotypic variability of PD, these correlations will focus on clinical features associated with disease progression, non-motor symptoms and motor complications. Genetic association studies will be conducted to identify new genetic risk factors for PD. In informative families new causal PD genes will be identified using a positional cloning strategy. The combination of objective and longitudinal clinical data on disease progression in a genetically well-characterized population of PD patients, is a major asset of the project.

Researcher(s)

• Promoter: Cras Patrick
• Co-promoter: Van Broeckhoven Christine
• Fellow: Crosiers David

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative brain disorder. Five causal genes (SNCA, LRRK2, PARK2, PINK1 and DJ1) leading to familial PD have already been identified. Variations in these genes have also been shown to increase susceptibility for sporadic PD. In my project, I am prospectively recruiting a population of familial and sporadic PD patients. Detailed phenotypic characterization of the patients is performed with standardized clinical scales at different time intervals. Genetic variations (simple and complex mutations) in the known causal genes will be identified and genotype-phenotype correlations will be established. Since disease progression is an important part of the phenotypic variability of PD, these correlations will focus on clinical features associated with disease progression, non-motor symptoms and motor complications. Genetic association studies will be conducted to identify new genetic risk factors for PD. In informative families new causal PD genes will be identified using a positional cloning strategy. The combination of objective and longitudinal clinical data on disease progression in a genetically well-characterized population of PD patients, is a major asset of the project.

Researcher(s)

• Promoter: Cras Patrick
• Co-promoter: Van Broeckhoven Christine
• Fellow: Crosiers David

Research team(s)

• Translational Neurosciences (TNW)

Project type(s)

• Research Project