Parkinson's disease Nervous System Diseases
Conditions
Interventions
Participants will undergo clinical (motor, neuropsychiatric and cognitive) and imaging assessments and will donate biological samples including blood (e.g. plasma, Peripheral blood mononuclear cells (
Sponsors
University of Dundee
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Parkinson’s disease group: 1. Age >/=18 years 2. Willingness to undergo genetic testing 3. Able to provide informed consent 4. Diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria for clinically established PD 5. Br???ki???i? and resting tremor or rigidity Additional inclusion criteria for PD subgroups: 1. Genetic PD: confirmation of carrier status of a pathogenic or probable pathogenic variant in LRRK2, VPS35, Rab32, GBA1 or other monogenic form of PD. 2. Non-genetic PD (Idiopathic PD): absence of carrier status of a pathogenic or probable pathogenic variant in LRRK2, VPS35, Rab32, GBA1 or other monogenic form of PD. Non-Parkinson’s disease group: 1. Age >/=18 years 2. Willingness to undergo genetic testing 3. Able to provide informed consent Additional inclusion criteria for non-PD subgroups: 1. No PD and no genetic carrier status for PD (‘healthy controls’) 2. Absence of carrier status of a pathogenic or probable pathogenic variant in LRRK2, VPS35, Rab32, GBA1 or in any other clearly PD-related gene 3. Absence of a first-degree relative with PD (e.g., biological parent, sibling, child) or multi-incident family history of PD No PD but non-manifesting pathogenic variant carrier status: 1. Confirmation of carrier status of a pathogenic or probable pathogenic variant in LRRK2, VPS35, Rab32, GBA1 or other monogenic form of PD No PD but positive family history of PD: 1. First-degree relative with PD (e.g., biological parent, sibling, child) or multi-incident family history of PD 2. Unknown genetic carrier status of a pathogenic or probable pathogenic variant in LRRK2, VPS35, Rab32, GBA1 or other monogenic form of PD
Exclusion criteria
Exclusion criteria: Exclusion criteria for all participants with PD: 1. A clinical diagnosis of dementia as determined by the investigator 2. Clinical evidence of atypical Parkinsonism (e.g., multiple-system atrophy or progressive supranuclear palsy) or evidence of drug-induced Parkinsonism 3. Previously obtained Magnetic Resonance Imaging (MRI) scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator) 4. Any other reason (medical or psychiatric condition or lab abnormality) that, in the opinion of the investigator, would render the participant unsuitable for study enrollment 5. Participation in a clinical trial testing an investigational medicinal product for PD that could interfere with the study investigations, e.g. LRRK2 or lysosome targeting IMPs (in the opinion of the investigator) Exclusion criteria for MRI and DAT imaging with PD: 1. Pregnant, lactating or planning pregnancy during the study. Pregnancy test to be carried out on day of scan for women of childbearing potential. Iodine allergy is exclusionary Exclusion criteria for all participants without PD: 1. Symptomatic PD syndromes due to either drugs (e.g., metoclopramide, flunarizine, neuroleptics) or metabolic disorders (e.g., Wilson’s disease), encephalitis 2. Clinical evidence of atypical Parkinsonism (e.g., multiple-system atrophy or progressive supranuclear palsy) 3. A clinical diagnosis of dementia as determined by the investigator 4. Previously obtained Magnetic Resonance Imaging (MRI) scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator) 5. Any other reason (medical or psychiatric condition or lab abnormality) that, in the opinion of the investigator, would render the participant unsuitable for study enrollment Exclusion criteria for MRI and DAT imaging without PD: Pregnant, lactating or planning pregnancy during the study. Pregnancy test to be carried out on day of scan for women of childbearing potential. Iodine allergy is exclusionary
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Lysosomal lipids, metabolites and proteins in enriched lysosomal fractions from peripheral blood immune cells, measured using targeted and untargeted mass spectrometry in tagless LysoIP samples isolated from peripheral blood mononuclear cells (PBMCs) and monocytes at a single cross-sectional timepoint 2. LRRK2 levels and LRRK2 kinase activity in peripheral blood immune cells, measured using a targeted mass spectrometry assay in peripheral blood monocytes and neutrophils 3. Presence of misfolded, aggregation-prone alpha-synuclein species, measured using an alpha-synuclein seed amplification assay in cerebrospinal fluid and in skin homogenates collected at the study visit | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. BMP (bis(monoacylglycerol)phosphate) levels in urine, measured using targeted mass spectrometry from urine samples collected at a single cross-sectional timepoint 2. Mass-spectrometry profiles in cerebrospinal fluid (CSF), measured using data-independent acquisition (DIA) mass spectrometry from CSF collected at the study visit 3. Mass-spectrometry profiles in plasma, measured using high-resolution mass spectrometry-based lipidomics from plasma collected at a single cross-sectional timepoint 4. Mass-spectrometry profiles in urine, measured using untargeted ultra-high performance liquid chromatography – mass spectrometry (UHPLC-MS) from urine samples collected at the study visit 5. Genetic variants associated with Parkinson’s disease, measured using next-generation sequencing (NGS) from genomic DNA isolated from whole blood at the study visit | — |
Countries
Scotland, United Kingdom
Contacts
Public ContactFrancesca;Tiffany Tonelli;Stewart
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Outcome results
None listed