The overall goal of this protocol is to investigate [18F]DPA-714 binding in prodromal and early manifest Parkinson's Disease (PD) and to determine the baseline and change from baseline in [18F]DPA-714 binding in PD participants during a 24-month interval.

Primary Objectives

• To compare [18F]DPA-714 binding in prodromal and manifest PD and healthy volunteers.
• To determine the longitudinal change in [18F]DPA-714 during a 24-month interval for prodromal and early initially untreated PD participants.

Secondary Objectives

• To evaluate the correlation between baseline [18F]DPA-714 and PPMI clinical and biomarker outcomes.
• To evaluate the correlation between the longitudinal change of [18F]DPA-714 and PPMI clinical and biomarker outcomes
• To acquire safety data following injection of [18F]DPA-714

Inclusion Criteria:

• A prodromal PD and Healthy participant enrolled in PPMI Clinical protocol

• A PD participant enrolled in PPMI Clinical protocol who has not started symptomatic treatment at time of enrollment or in the first 2 years of participation.

• Able to provide informed consent

• Must have screening genetic testing documenting high binder at the at the known TSPO gene polymorphism (rs6971)

• 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]DPA-714

• 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]DPA-714 on day of PET scan.

Exclusion Criteria:

• Exposure to a total effective dose equivalent of 50 millisievert (mSv) for the whole body, which is the annual limit established by the US Code of Federal Regulations , during the past year.
• Any other medical or psychiatric condition or lab abnormality, which in the opinion of the Site Investigator might preclude participation.