Study to explore the use of glucocerebrosidase activity and other glycosphingolipids as potential biomarkers of GCase activation in healthy subjects and patients with Parkinson's Disease with and without a mutation in the GBA gene

Group 1, Inclusion criteria;;1. Signed informed consent prior to any study-mandated procedure.
2. Healthy male and female volunteers, 18 to 70 years of age, of which 50% is *55 years of age, inclusive at screening. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical history and clinical laboratory parameters (hematology, blood chemistry and urinalysis).
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive at screening, and with a minimum weight of 50 kg.
4. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions. ;Group 2 & 3, Inclusion criteria;;1. Signed informed consent prior to any study-mandated procedure.
2. Diagnosis of PD at least 6 months prior to screening. The diagnosis requires: the presence of at least 2 of the 4 cardinal clinical manifestations of the disease, tremor, rigidity, bradykinesia, and disturbances of posture or gait.
3. A score of 1-4 on Hoehn & Yahr Scale.
4. Group 2: Confirmed mutation in the glucocerebrosidase (GBA1) gene.
5. Group 3: Confirmed wild type glucocerebrosidase (GBA1) gene.
6. Mini Mental State Exam score (MMSE) ><= 18 and assessed by treating neurologist as mentally competent.
7. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, and with a minimum weight of 50 kg at screening.
8. Has the ability to communicate well with the Investigator in the Dutch language and willing to comply with the study restrictions.

Group 1, Exclusion criteria;;1. Any recent (within 7 days) infectious disease;
2. Positive Hepatitis B surface antigen (HBsAg), Hepatitis B antibodies, Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
3. Use of any medications (prescription or over-the-counter [OTC]), within 14 days of screening, or less than 5 half-lives (whichever is longer). Exceptions are paracetamol (up to 4 g/day) and ibuprofen (up to 1 g/day). Other exceptions will only be made if the rationale is clearly documented by the investigator;
4. Participation in an investigational drug or device study within 3 months prior to first sampling.
5. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillizers, or any other addictive agent;
6. Positive test for drugs of abuse at screening or pre-dose (in case of a positive test result, the test may be repeated once);
7. Alcohol will not be allowed from at least 24 hours before screening;
8. Smoker of more than 10 cigarettes per day prior to screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking whilst in the unit;
9. Is demonstrating excess in xanthine consumption (more than eight cups of coffee or equivalent per day;
10. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during the study;
11. If a woman, pregnant, or breast-feeding, or planning to become pregnant during the study;
12. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.;Group 2 & 3, Exclusion criteria;;1. Evidence of any active or chronic disease or condition other than PD that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history and clinical laboratory parameters (hematology, blood chemistry and urinalysis).
2. Positive Hepatitis B surface antigen (HBsAg), Hepatitis B antibodies, Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
3. History of recent major surgery (within 60 days of screening).
4. Atypical or secondary parkinsonism (in the judgment of the PI).
5. Any recent (within 7 days) infectious disease;
6. Participation in an investigational drug or device study within 3 months prior to first dosing.
7. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units of alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillizers, or any other addictive agent
8. Positive test for drugs of abuse at screening or pre-dose.
9. Alcohol will not be allowed from at least 24 hours before screening;
10. Smoker of more than 10 cigarettes per day prior to screening or who use tobacco products equivalent to more than 10 cigarettes per day and unable to abstain from smoking whilst in the unit.
11. Is demonstrating excess in xanthine consumption (more than eight cups of coffee or equivalent per day
12. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening or intention to donate blood or blood products during the study.
13. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.