Molecular and Functional Imaging in SNCA, Parkin and PINK1

Inclusion Criteria (for all subjects):

- All subjects must be judged by the investigator able to understand the nature, design, and procedures of the study and must be able to provide a signed and dated informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations.

- All subjects must be willing and able to comply with scheduled visits, required study procedures and laboratory tests.

- All subjects must be able to travel to the research sites for the study procedures.

- For female subjects: They must be either of non-childbearing potential (either surgically sterile or post- menopausal - defined as 12 months of spontaneous amenorrhea), or, if of childbearing potential, subjects must demonstrate to be non-pregnant (as demonstrated by negative urine β-HCG test at screening), non-breastfeeding.

- All subjects must comply with highly effective contraceptive measures. A highly effective contraceptive measure is defined as a measure that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods are listed in more detail below:

Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation;

Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation:

Intrauterine device (IUD) Intrauterine hormone-releasing system (IUS) Bilateral tubal occlusion Vasectomised partner Sexual abstinence

- For sexually active male subjects, they must agree to use condoms to protect their partners from becoming pregnant for the duration of the study and for 3 months after the last administration of PET or SPECT ligands. They must also agree to ensure that they and their partners are routinely using a medically approved contraceptive method. It is important that male subjects not impregnate others for the duration of the study and for 3 months after the last administration of PET or SPECT ligands.

- All subjects must have adequate visual and auditory acuity according to investigator's judgement to complete the psychological testing.

- All subjects must have no use of medications with known interaction with serotonergic transmission (e.g. selective serotonin reuptake inhibitors, tricyclic antidepressant, triptans, etc).

- For subjects taking any drugs that might interfere with dopamine transporter SPECT imaging (neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative) must be willing and able from a medical standpoint to hold the medication for at least 5 half-lives prior to screening DaTSCAN imaging.

Exclusion Criteria (for all subjects):

- Subjects lacking capacity according to investigator judgement.

- Subjects with a clinical diagnosis of dementia as determined by the investigator.

- Current treatment with anticoagulants (e.g. coumadin, heparin) that might preclude safe completion of the lumbar puncture.

- Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.

- Use of any of the following drugs that might interfere with dopamine transporter SPECT imaging: neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 5 months of Screening.

- Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).

- History of cancer within the last 5 years, with the exception of non-metastatic basal cell carcinoma of the skin.

- Subjects with current or recent history of drug or alcohol abuse/dependence.

- Contraindication to MRI, such as presence of metal devises or implants (e.g. pacemaker, vascular- or heart- valves, stents, clips), metal deposited in the body (e.g. bullets or shells), or metal grains in the eyes;

- Claustrophobia or history of back pain that makes prolonged laying on the PET or MRI scanner intolerable.

- Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).

- Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.