Study to Evaluate a Potential PET Radioligand for Imaging Alpha-synuclein Deposits in the Brain

Inclusion Criteria: * Participants is able to provide written informed consent, which must be obtained before any assessment is performed. * Female participants must not be of childbearing potential, or agree to use contraception and not donate eggs if of childbearing potential. At the discretion of the Investigator, participants without documentation of non-childbearing potential may receive pregnancy testing. * A woman is considered to be of childbearing potential if postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (ie, removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the PI (eg, Müllerian agenesis). * Women of childbearing potential must commit to remain abstinent (refrain from heterosexual intercourse) or use 2 forms of birth control, 1 of which is a barrier contraception method, for the duration of the study and 30 days after study completion. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. * Women of childbearing potential must commit to not donate ovum for the duration of the study and 30 days after study completion. * Male participants and their partners of childbearing potential must commit to the use of 2 methods of contraception, 1 of which is a barrier method for male participants for the study duration and 90 days after study completion. * Male participants must not donate sperm for the study duration and for 90 days after study completion. * Willing and able to cooperate with study procedures. * For participants receiving arterial cannulation, adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test) and blood clotting (PT and PTT). * If participant takes bupropion, participant must agree to hold this medication for at least 12 hours prior to DaTscan imaging (if performed). Additional Inclusion Criteria for healthy volunteers: * Males and females aged ≥ 21 years. * Healthy with no clinically relevant finding on physical examination at Screening and upon reporting to the clinic for the \[18F\]MNI-1216 (\[18F\]ACI-12589) Imaging Visit. * No family history of α-synucleinopathy, including PD, or other early-onset neurological disease associated with dementia. * No personal history of clinically significant neurologic and/or psychiatric disorders. * No evidence of dopamine transporter deficit on DaTscan performed either as part of Screening or on previously acquired DaTscan (within 6 months prior to signing consent). * Have a Montreal Cognitive Assessment (MoCA) score ≥ 26. * No cognitive impairment as judged by the PI. Additional Inclusion Criteria for Participants with α-synucleinopathy: * Males and females aged ≥ 40 years. * Participants diagnosed with any of the following: * Idiopathic Parkinson's Disease * Parkinson's Disease with genetic risk factor (except leucine-rich repeat kinase 2 \[LRRK2\] mutation) * Dementia with Lewy Bodies * Multisystem Atrophy * A brain MRI consistent with a diagnosis of α-synucleinopathy, with no evidence of focal disease to account for the participant's neurological symptoms or MRI exclusion criteria listed below under "Exclusion Criteria". * Evidence of dopamine transporter deficit on DaTscan performed either as part of Screening or on previously acquired DaTscan. * Medications taken for symptomatic treatment of α-synucleinopathy must be maintained on a stable dosage regimen for at least 30 days before Screening Visit. * Ability to tolerate lying in the scanner for up to \~180 minutes without excessive head or jaw tremor or dyskinesia sufficient to cause significant motion artifact on the PET scans. Exclusion Criteria: * Current or prior history of any alcohol or drug abuse in the past 2 years. * Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness. * Known history of hypersensitivity, including hypersensitivity to the active substances used for DaTscan, \[18F\]MNI-1216 (\[18F\]ACI-12589) and \[18F\]florbetapir or derivatives, or to any of the associated excipients. * Participant has received an investigational drug within 30 days or five half-lives prior to the baseline assessments, whichever is longer. * Prior participation in other research protocols or clinical care during the past year that would result in radiation exposure to an effective radiation dose exceeding the acceptable annual limit established by the US Federal Guidelines (effective dose of 50 mSv, including the procedures in this clinical protocol). * Pregnant, lactating or breastfeeding. * Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, alternative neurological, immunodeficiency, pulmonary, or other disorder or disease. * Unsuitable veins for repeated venipuncture. * MRI with clinically significant structural abnormalities. * Implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, central nervous system (CNS) aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI. * Participant has received treatment with a drug, antibody or vaccine targeting α-synuclein. * Ongoing treatment with methylphenidate, modafinil, metoclopramide, alpha methyldopa, reserpine, or amphetamine derivative is prohibited 24 hours or during a period corresponding to 5 half-lives of the compound, whichever longer, prior to DaTscan imaging. * Treatment with any antihemostasis medication (eg, warfarin, heparin, thrombin inhibitors, Factor Xa inhibitors, streptokinase, urokinase, tissue plasminogen activators) within 2 weeks of the planned arterial cannula placement (if performed) for either the baseline or retest imaging. Additional Exclusion Criteria for Participants with α-synucleinopathy: * Evidence of early frequent falls or eye movement abnormalities consistent with PSP. * Individuals with known LRRK2 mutation (based on previous source documentation).