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 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 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 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.
