Proof of Mechanism Study to Evaluate Binding of Alfa-synuclein

Inclusion Criteria for all Participants: * Participant is able to provide informed consent, which must be obtained before any study procedures are performed. * Female participants must not be of childbearing potential, or if they are of childbearing potential must agree to use contraception and not donate eggs. * A woman is considered to be of childbearing potential if she is 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 principal investigator (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 ova for the duration of the study and 30 days after study completion. * Male participants with 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 who will have arterial cannulation performed, adequate circulation to the hand for safe placement of arterial line (as determined by Allen's test) and blood clotting (Prothrombin Time \[PT\] and Partial Thromboplastin Time \[PTT\]). * If participant takes bupropion, participant must agree to hold this medication for at least 12 hours prior to DaTscan imaging (if performed). * OTC medication (except acetaminophen), herbal supplements, dietary supplements, or vitamins approved by the Investigator, must be stable within 2 weeks prior to initial dosing. Additional inclusion criteria for participants with MSA: * Males and females aged ≥ 50 years. * Diagnosis of probable MSA, according to Consensus Clinical Diagnostic Criteria for MSA and a consistent MRI scan performed either at Screening or previously acquired. * Evidence of dopamine transporter (DaT) deficit on DaTscan performed either as part of Screening or previously acquired. * Medications taken for symptomatic treatment 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 2 hours, without excessive head or jaw tremor or dyskinesia sufficient to cause significant motion artifact on the PET scans. * Prescription drugs approved by the Investigator must be stable within 4 weeks prior to initial dosing. Additional inclusion criteria for participants with PD: * Males and females aged ≥ 50 years. * Clinical diagnosis of PD (early, moderate, or severe) for \> 6 years, according to medical history, and L-DOPA responsive. * Evidence of DaT deficit on DaTscan performed either as part of Screening or previously acquired. * Medications taken for symptomatic treatment 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 2 hours, without excessive head or jaw tremor or dyskinesia sufficient to cause significant motion artifact on the PET scans. * Prescription drugs approved by the Investigator must be stable within 4 weeks prior to initial dosing. Additional inclusion criteria for healthy volunteers: * Males and females aged ≥18 years. * Healthy with no clinically relevant finding on physical examination at Screening. * 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 cognitive impairment as judged by the Investigator. Exclusion Criteria for all participants: * Pregnant, lactating or breastfeeding. * Current or prior history of any alcohol or drug abuse in the past 2 years to be verified by urine drug screen. * Laboratory tests with clinically significant abnormalities and/or clinically significant unstable medical illness. * History of immunodeficiency diseases, including a positive HIV test result. * A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody test result. * Known history of hypersensitivity, including hypersensitivity to the active substances used for DaTscan, \[18F\]UCB2897, and/or \[18F\]florbetapir or derivatives, or to any of the associated excipients. * 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. * Are claustrophobic or otherwise unable to tolerate the imaging procedure. * MRI with clinically significant structural abnormalities, other than those expected for MSA or PD for those participants. * 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 an investigational drug within 30 days or five half-lives prior to Day 1, whichever is longer. * Participant has received treatment with a drug, antibody or vaccine targeting α-synuclein. * Prior participation in other research protocols, clinical care, or occupational exposure 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). * For participants receiving DaTscan imaging, 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. For participants who will have arterial blood sampling, 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. • Participant is, in the opinion of the Investigator, unsuitable in any other way to participate in this study. Additional exclusion criteria for healthy volunteers: * BMI \< 16 or \> 35. * The participant is currently exposed to nicotine products or had regular nicotine exposure within a six-month period, to be verified by urine cotinine screening. * Use of any prescription drugs (except approved forms of birth control) or herbal supplements, within 4 weeks prior to Screening. Additional exclusion criteria for participants with MSA: • Evidence of early frequent falls or eye movement abnormalities consistent with progressive supranuclear palsy (PSP). Additional exclusion criteria for participants with PD: * The participant is currently exposed to nicotine products or had regular nicotine exposure within a six-month period, to be verified by urine cotinine screening. * Evidence of early frequent falls or eye movement abnormalities consistent with PSP.