The study is a longitudinal, multi-center study to assess progression of [18F] AV-133 imaging in Prodromal PD participants. Participants will be followed for up to 24 months. Approximately 100 Prodromal participants will be recruited from up to 10 sites. Participants will be comprehensively assessed at baseline and follow up. Participants will undergo imaging assessments with [18F] AV-133 and clinical (motor, neuropsychiatric, cognitive and imaging and biomarker) assessments (conducted under the PPMI Clinical protocol).

The Parkinson's Progression Marker Initiative (PPMI) is an observational, international, multi-center study designed to identify PD progression biomarkers both to improve understanding of disease etiology and course and to provide the necessary tools to enhance the likelihood of success of therapeutics studies to slow PD progression (ClinicalTrials.gov Identifier: NCT01141023). A key focus of PPMI is to identify biomarkers during the period when PD neurodegeneration is already present, but symptoms of PD have not yet occurred. This prodromal cohort would enable us to investigate PD biomarker signatures prior to onset of typical symptoms of PD. The study is a longitudinal, multi-center study to assess progression of [18F]AV-133 imaging in Prodromal PD participants. The PPMI 015 study will enroll participants from the PPMI Clinical (002) study. Participants will be followed annually for up to 24 months.

Approximately 100 Prodromal participants will be recruited from up to 10 sites. Participants will be comprehensively assessed at baseline and follow up.

Participants will undergo [18F]AV-133 PET imaging targeting the vesicular monoamine transporter. All participants will undergo an initial [18F]AV-133 PET imaging scan at baseline with repeat imaging at 12 months and 24 months.

Inclusion Criteria:

1. A Prodromal PD participant, over the age of 18, confirmed as eligible to proceed to PPMI Clinical Baseline visit.

2. Able to provide informed consent.

3. Male or Female (females must meet additional criteria specified below as applicable)

   • Females must be of non-childbearing potential or using a highly effective method of birth control 14 days prior to until at least 24 hours after injection of 18F-AV-133

     • Non-childbearing potential is defined as a female that must be either postmenopausal (no menses for at least 12 months prior to PET scan) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy).
     • Highly effective method of birth control is defined as practicing at least one of the following: A birth control method that results in a less than 1% per year failure rate when used consistently and correctly, such as oral contraceptives for at least 3 months prior to injection, an intrauterine device (IUD) for at least 2 months prior to injection, or barrier methods, e.g., diaphragm or combination condom and spermicide. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.

   • Females of childbearing potential must not be pregnant, breastfeeding or lactating.

     • Includes a negative urine pregnancy test prior to injection of 18F-AV-133 on day of PET scan.

Exclusion Criteria:

1. Received any of the following medications that might interfere with 18F- AV-133 PET imaging: tetrabenazine (TBZ) or methylphenidate, reserpine, or amphetamine derivative, within 1 month prior to the Baseline 18F-AV-133 injection.
2. Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.