Molecular and Functional Imaging in Monogenic PD.

Inclusion Criteria:

• 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 datedinformed consent in accordance with Good Clinical Practice (GCP), InternationalConference on Harmonization (ICH), and local regulations.

• All subjects must be willing and able to comply with scheduled visits, requiredstudy 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 (eithersurgically sterile or post- menopausal - defined as 12 months of spontaneousamenorrhea), or, if of childbearing potential, subjects must demonstrate to benon-pregnant (as demonstrated by negative urine β-HCG test at screening),non-breastfeeding.

• All subjects must comply with highly effective contraceptive measures. A highlyeffective contraceptive measure is defined as a measure that can achieve a failurerate of less than 1% per year when used consistently and correctly. These methodsare 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 theirpartners from becoming pregnant for the duration of the study and for 3 months afterthe last administration of PET or SPECT ligands. They must also agree to ensure thatthey and their partners are routinely using a medically approved contraceptivemethod. It is important that male subjects not impregnate others for the duration ofthe study and for 3 months after the last administration of PET or SPECT ligands.

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

• All subjects must have no use of medications with known interaction withserotonergic transmission (e.g. selective serotonin reuptake inhibitors, tricyclicantidepressant, triptans, etc).

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

Exclusion Criteria:

• 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. warfarin, heparin) that might precludesafe completion of the lumbar puncture.

• Condition that precludes the safe performance of routine lumbar puncture, such asprohibitive lumbar spinal disease, bleeding diathesis, or clinically significantcoagulopathy or thrombocytopenia.

• Use of any of the following drugs that might interfere with dopamine transporterSPECT 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 (dietarysupplements taken outside of a clinical trial are not exclusionary, e.g., coenzymeQ10).

• History of cancer within the last 5 years, with the exception of non-metastaticbasal 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 MRIscanner intolerable.

• Previously obtained MRI scan with evidence of clinically significant neurologicaldisorder (in the opinion of the Investigator).

• Any other medical or psychiatric condition or lab abnormality, which in the opinionof the investigator might preclude participation.