Title Promoter Affiliations Abstract "Clinical and genetic epidemiology of Parkinson's disease: focus on disease progression and non-motor symptoms." "Patrick Cras" "VIB CMN - Neurodegenerative Brain Diseases Group, Translational Neurosciences (TNW)" "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." "Clinical and genetic epidemiology of Parkinson's disease: focus on disease progression and non-motor symptoms." "Patrick Cras" "VIB CMN - Neurodegenerative Brain Diseases Group, Translational Neurosciences (TNW)" "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." "Dissecting the link between astrocyte diversity and PD risk” to investigate how neurodegenerative diseases, including Parkinson’s disease, intersect with regional aspects of astrocyte identity" "Patrik Verstreken" "Verstreken Lab" "Studying how the brain operates and how brain function is affected by neurodegenerative diseases, specifically Parkinson’s disease and Tauopathies, analysing neuronal communication abd synaptic survival." "Longitudinal measurement of synaptic density to monitor progression of Parkinson's disease and Huntington's disease" "Wim Vandenberghe" "Laboratory for Parkinson Research, Nuclear Medicine & Molecular Imaging" "Increasing evidence from cell or animal models and postmortem human studies suggests that synaptic pathology is important in the early disease pathophysiology of Parkinson’s (PD) and Huntington’s disease (HD). PET imaging with 11C‑UCB‑J, targeting the presynaptic protein SV2A, provides an in vivo marker for synaptic density in the human brain. This thesis reports two multimodal imaging studies in people with early PD and early HD respectively, both with an age- and gender-matched healthy control group. The aim of these studies was to assess regional synaptic changes in the human brain and its clinical correlates in vivo in early PD patients and early HD mutation carriers respectively and to evaluate the suitability of 11C‑UCB‑J PET as diagnostic and/or prognostic biomarker in these groups.  For the longitudinal PD study, 30 patients with PD and 20 healthy controls were included at baseline, and 27 PD patients and 18 controls completed all follow-up visits after approximately 2 years. At baseline and follow-up, 11C‑UCB‑J PET was combined with 18F-FE-PE2I PET, a marker for quantification of dopaminergic presynaptic terminals, and MRI. In addition, all participants underwent a comprehensive assessment of clinical motor and non-motor manifestations. Cortical and subcortical volumes of interest (VOIs) were delineated based on individual 3D MRI. VOI- and voxel-based analyses were performed. All PET image data were analyzed without and with correction for partial volume effects, and statistical analyses were corrected for multiple comparisons. At baseline, clinical characterization demonstrated that PD patients had more severe motor signs and symptoms, cognitive impairment, anxiety, sleep problems and autonomic symptoms compared to controls. Over 2 years, only motor impairment significantly worsened in PD. With 11C‑UCB‑J PET, a significant cross-sectional SV2A loss in the PD group was found in the substantia nigra only. No significant regional SV2A loss could be demonstrated over 2 years. By contrast, 18F-FE-PE2I PET confirmed a profoundly decreased striatal and nigral DAT binding in early PD compared to controls, most prominent in putamen. After 2 years, there was a further significant annual decrease in the striatum in PD, which also was significantly greater than in controls. No correlations between regional decrease in 11C‑UCB‑J or 18F-FE-PE2I binding and clinical scores were found at baseline or longitudinally.The cross-sectional HD study cohort consisted of 18 early HD mutations carriers (7 premanifest, 11 manifest [7 Shoulson & Fahn stage 1 and 4 stage 2]) and 15 healthy controls. The longitudinal study is still ongoing. SV2A PET was combined with 18F‑FDG PET, given the suspected link between synaptic activity and brain glucose metabolism, and MRI. Motor and non-motor functioning was also assessed in all study participants. Similar to the PD study, cortical and subcortical volumes of interest (VOIs) were delineated based on individual 3D MRI. VOI- and voxel-based analyses were performed. All PET image data were analyzed without and with correction for partial volume effects, and statistical analyses were corrected for age, gender and multiple comparisons. Compared to controls, HD mutation carriers had significantly higher motor scores and more cognitive impairment. 18F‑FDG PET showed regional hypometabolism limited to the striatum in the HD group, whilst 11C‑UCB‑J PET imaging demonstrated widespread loss of presynaptic terminals in striatum, cerebral cortex and cerebellum. A subgroup analysis indicated that SV2A loss was limited to the striatum in premanifest HD, but was much more widespread with also cortical involvement in manifest HD. In the HD group, putaminal SV2A loss was correlated with motor signs.In conclusion, this thesis provides new insights into synaptic alterations in people with early PD and early HD in vivo. In early PD, 18F‑FE‑PE2I PET provides a robust biomarker for cross-sectional and longitudinal nigrostriatal dopaminergic terminal loss in vivo in early PD, but does not provide a quantitative surrogate endpoint for clinical impairment or progression. 11C‑UCB‑J PET showed cross-sectional loss of SV2A in substantia nigra in early PD, but no longitudinal changes nor correlations with clinical symptoms were found. Therefore, 11C‑UCB‑J binding does not seem suitable as a diagnostic or prognostic biomarker in early PD. In early HD, SV2A loss extends from the striatum in premanifest HD to widespread cortical and subcortical loss in the manifest phase, while glucose hypometabolism is limited to the striatum in both premanifest and manifest HD. Furthermore, motor symptoms correlated inversely with putaminal 11C‑UCB‑J binding. Taken together, SV2A availability as measured by PET could be a promising diagnostic or monitoring imaging biomarker in people with early HD. A longitudinal 2-year follow-up study is ongoing." "Prospective head-to-head comparison of cardiac [18F]-MFBG PET versus [123I]-MIBG SPECT in the differentiation between Parkinson’s disease and multiple system atrophy and between dementia with Lewy bodies and Alzheimer’s disease." "Koen Van Laere" "Nuclear Medicine & Molecular Imaging, Laboratory for Parkinson Research" "The present study will be sponsored by the KU Leuven with Koen Van Laere, Prof MD PhD DSc, as its principal investigator. The purpose is a prospective head-to-head comparison of [18F]-MFBG cardiac innervation in the differential diagnosis of Parkinson’s disease and dementia with Lewy Bodies, compared to cardiac innervation measured by [123I]-MIBG cardiac imaging and brain dopamine transporter availability measured by [18F]-PE2I PE. Primary objectives: 1. Feasibility: To assess the reduction and discriminatory accuracy in myocardial uptake of [18F]-MFBG in PD and DLB, versus expected normal values in AD, CON, and MSA-P. 2. Non-inferiority : Assess that [18F]-MFBG has at least similar accuracy in discriminating PD from MSA-P compared to [123I]-MIBG SPECT, and in discriminating DLB from AD compared to [123I]-MIBG SPECT. Secondary objectives: 3. Effect size (ES) : Assess that the reduction and ES in myocardial uptake of [18F]-MFBG in PD and DLB is larger compared to [123I]-MIBG SPECT and [123I]-MIBG planar scintigraphy. 4. Relation to brain DAT : Assess that the reduction in myocardial uptake of [18F]-MFBG in PD and DLB is directly related to the reduction in [18F]-PE2I binding for PD and DLB in early to moderate disease. 5. Relation to autonomic dysfunction: Assess that the reduction in myocardial uptake of [18F]-MFBG in PD and DLB is related to autonomic dysfunction. 6. Regional myocardial variation: Assess that the regional pattern of reduced [18F]-MFBG uptake is different between PD/DLB and controls. The trial is designed as a multicentric prospective interventional study with three cohorts and in total 5 panels (1/ CON, 2/ PD vs. MSA-P, 3/ DLB vs AD). Each subject will undergo three PET/SPECT including 1 brain MRI (PET/MR) scans. There will also be a microdosing study for all tracers." "Unraveling cell-type-specific disease modifier pathways in familial Parkinson’s disease" "Patrik Verstreken" "Laboratory of Neuronal Communication (VIB-KU Leuven)" "Parkinson’s disease (PD) is a neurodegenerative disorder with only symptomatic treatments but no cures. PD hallmarks are hypokinesia, rigidity, and tremor resulting from dopaminergic cell loss. In addition, PD is characterized by several non-motor symptoms which indicate that also other cell types significantly contribute. Yet we do not have a comprehensive overview of all cell types relevant to PD and the underlying pathways. To study this question in an unbiased and brain-wide manner, my host laboratory performed single-cell RNA sequencing across entire fly brains of Drosophila PD models and revealed >10 cell types that are highly transcriptionally deregulated, even at an early time point prior to dopaminergic impairment. This project will build on these results and aims to relate this ‘transcriptional vulnerability’ to neuronal function to learn from these cell-type specific transcriptional responses on how to improve cellular health. I will assess neuronal excitability and synaptic vesicle cycling by means of sensitive live imaging in transcriptionally deregulated cell types. I will also assess cell-type specific neurodegeneration by means of automated neuronal counting and test whether further genetically up-/downregulating deregulated genes within these cell types is improving cellular function. Collectively, these experiments will yield novel cell types underlying PD and suggest new cell type specific disease modifiers that will be assessed in the future in human system." "Druwé-Eerdekens & Van Ael and the Vlaamse Parkinson Liga: ""'A Novel Training Method to Reduce Fall Risk in People with Parkinson’s Disease: The Role of the Balance Organ" "geen abstract" "Customized nutrition for Parkinson's disease patients" "Christophe Matthys" "Clinical and Experimental Endocrinology" "Parkinson's disease is the second most prevalent neurodegenerative disorder, characterized by both motor and non-motor deficits. It's cause has not yet been elucidated and no treatment has yet been discovered. The current therapies predominantly relieve motor symptoms. The non-motor deficits include sensory symptoms such as the loss of taste and smell, but also various gastro-intestinal symptoms, including dysphagia, nausea and bloating. In these symptoms diet could play a role in symptom relief. The objective of this research project is to evaluate the potential role of a customized diet as an adjuvant therapy in Parkinson's disease This was achieved by through 2 research lines. The first research line involves the direct impact of diet on Parkinson's disease, with a focus on the use of thickened liquids in dysphagia and the identification of food odors by hyposmic patients. Bolus modification is one of the management strategies of dysphagia, which consists of softening solids and thickening liquids to ensure safe swallowing. There are already different thickening agents on the market, both starch- and gum-based, however, they have a negative impact on taste and texture. This results in aversion of patients towards the therapy and low treatment compliance. The objective is to improve the taste, aroma and texture of thickened liquids. This may lead to a higher compliance and consequently an improved quality of life. Parkinson's patients often already suffer from hyposmia, impacting the flavor perception of food and reducing patients' quality of life. Identification of food odorants that are well recognized by Parkinison's patients may aid in the development of aroma boosters.The second research line involves the indirect impact of diet, herein we take a closer look at the involvement of the gut-brain axis in the pathology of Parkinson's disease and the possible use of food-based therapies. The bacterially-produced short chain fatty acids are implied to have beneficial effects in Parkinson's disease, however short chain fatty acid-producing bacteria are reduced in Parkson's patients. The objective is to stimulate short chain fatty acid production in vitro in fecal samples of Parkinson's patients, using different types of dietary fiber. " "A profound study of gut homeostasis in Parkinson's disease." "Department of Internal Medicine and Pediatrics, Department of Biomedical molecular biology" "ParkinsonU+2019s disease (PD) is the second most common neurodegenerative disorder and due to the lack of early diagnosis and effective therapy, represents a large burden for our society and healthcare system. The last years, it became increasingly apparent that non-motor symptoms, including gastrointestinal dysfunction, precede the onset of the typical PD motor symptoms by over two decades. Moreover, emerging evidence suggests that PD, and more specifically the aggregation of alpha-synuclein syn), starts in the gut before spreading to the brain. Additionally, recent microbiome studies consistently showed microbiota differences between PD patients and healthy controls. However, detailed insights in how the microbiome affects the patientsU+2019 symptoms is lacking. The ultimate goal of this project is to address the impact of gut dysbiosis and the restoration of gut homeostasis by fecal microbiota transplantation (FMT) on the development and progression of PD. We will identify PD-specific changes in microbiota composition and gut inflammation and determine the effect of a U+2018microbiome-resetU+2019 approach through FMT in PD patients on the identified changes and more importantly on disease symptoms and progression. In parallel, we aim to elucidate the mechanism by which the microbiome affects PD disease onset and progression, using a mouse model of PD, focusing on the effect of the microbiome on syn expression, aggregation and spreading." "Do cognitive problems underlie motor deficits in Parkinson's Disease?" "Wim Notebaert" "Department of Experimental psychology" "ParkinsonU+2019s disease (PD) is characterized by motor symptoms such as tremor (for example, involuntarily shaking of a patientU+2019s leg) and postural instability. In addition, PD patients have difficulty learning new movement patterns. In this project, we will examine whether these motor problems may relate to problems in cognitive functioning. We will also study the role of medication in this relationship."