Testing a brain scan for Parkinson’s-related protein changes

Inclusion Criteria: * Healthy Controls inclusion criteria: 1. Enrolled in the PPMI 002 Clinical study as a healthy control participant 2. Any gender aged 50 to 75 years of age 3. Negative CSF α-synuclein seed amplification assay (SAA) 4. Previously acquired (since inclusion in PPMI) brain MRI without evidence of significant neurological pathology. 5. Movement Disorders Society- Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) score of \<6 at the last PPMI annual visit which is within the past 18 months. 6. Cognitively intact with Montreal Cognitive Assessment (MoCA) greater than or equal to 26 at the last PPMI annual visit which was within the past 18 months. * Parkinson's Disease and Prodromal PD inclusion criteria: 1. Enrolled in the PPMI 002 Clinical study as a Parkinson's Disease (PD) or Prodromal participant 2. Any gender aged 50 to 80 years of age 3. Positive CSF SAA 4. A current or previously acquired brain MRI (since the onset of motor symptoms for PD or since enrolled in PPMI for the prodromal PD) without evidence of significant neurological pathology other than changes expected for PD. 5. Montreal Cognitive Assessment (MoCA) greater than or equal to 24 at the last PPMI annual visit which was within the past 18 months. * Multiple System Atrophy (MSA) inclusion criteria: 1. Any gender aged 50 to 75 years of age 2. Clinically established MSA or Clinically Probable MSA according to the Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy (Wenning et al., 2022) 3. Positive CSF SAA 4. A current or previously acquired brain MRI (since the onset of motor symptoms attributed to MSA) without evidence of significant neurological pathology other than the pathology expected for MSA. 5. Evidence of nigrostriatal degeneration on DaTscan obtained at screening or on previously acquired imaging since the onset of the motor symptoms attributed to MSA. Exclusion Criteria: * All Cohorts: 1. Clinical evidence of other neurodegenerative diseases, such as Alzheimer's disease 2. Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation. 3. Received any of the following drugs: dopamine receptor blockers (neuroleptics), metoclopramide, lithium and reserpine, within 6 months of Baseline Visit. 4. Any other reason that in the opinion of the investigator, including abnormal labs, that could interfere with the safety with radiotracer injection, would render the participant unsuitable for the study enrollment. 5. Participation in an investigational drug trial targeting α-synuclein within the past 6 months prior to enrollment. 6. Currently being treated with and unable to safely hold antiplatelets (other than low dose aspirin up to 100mg/day) or anticoagulants prior to the procedure that might preclude safe attempt of Lumbar puncture, if applicable. 7. Condition that precludes the safe performance of routine lumbar puncture, if applicable, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant and uncorrected coagulopathy or thrombocytopenia. 8. Conditions or medications that preclude safe performance of imaging procedures (MRI or DaTscan), including but not limited to severe claustrophobia, MRI-incompatible metal implants, or known hypersensitivity to imaging agents. 9. Known hypersensitivity to DaTscan or iodine-containing compounds used as premedication for DaTscan. Participants with iodine sensitivity may still complete the imaging without iodine premedication at the investigator's discretion. 10. Use of medications known to interfere with DaTscan imaging (e.g., bupropion, amphetamines, methylphenidate, modafinil, alpha-methyldopa), unless the participant is willing and medically able to hold the medication for at least 5 half-lives or specified duration per investigators judgement prior to imaging.