Systemic Synuclein Sampling Study (S4)

Inclusion Criteria (PD subjects): * Male or female age 40 or older at the time of PD diagnosis. * Clinical diagnosis of PD based on bradykinesia plus one of the following: rest tremor or rigidity. * DAT deficit at screening based on visual interpretation of DaTSCAN™ imaging. * PD subjects will need to fall into one of the following stages: * Early untreated PD not requiring dopamine replacement medication (anticholinergics, MAO-B inhibitors and amantadine permitted), Hoehn and Yahr 1-2, \< 2 years from diagnosis. * Moderate PD responsive and currently treated with dopamine replacement therapy without evidence of motor fluctuations or dyskinesias. * Advanced PD with motor fluctuations or dyskinesias, \> 5 years from diagnosis. * Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations. * Willing and able to comply with scheduled visits, required study procedures and laboratory tests. Inclusion Criteria (HC subjects): * Male or female age 50 or older at the time of the screening visit * Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations. * Willing and able to comply with scheduled visits, required study procedures and laboratory tests. Exclusion Criteria (all subjects): * Has a history of cancer (other than basal and squamous cell skin cancers), autoimmune disorder, liver disease, or other hematological disorder within the past 5 years. * Current treatment with anticoagulants (e.g., Coumadin, heparin) that would preclude safe completion of the lumbar puncture (LP) and tissue biopsy procedures. * Current treatment with an antiplatelet agent (Plavix or aspirin \>325 mg/day). * Has a diagnosis of diabetes mellitus requiring either an oral agent or insulin therapy. * A bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia. * Has received botulinum toxin injections to the submandibular gland within the past year. * Has a condition that precludes safe performance of routine LP, such as prohibitive lumbar spinal disease. * Has a condition that precludes the safe performance of the flexible sigmoidoscopy procedure or may interfere with obtaining evaluable colonic tissue biopsies, including a prior colonoscopy with significant findings (e.g. polyp with a positive finding, ulcerative colitis, Crohn's disease, inflammatory disease). * Has a condition that precludes the safe performance of the submandibular gland procedure or may interfere with obtaining evaluable submandibular tissue biopsies, including any previous or active significant disease affecting the submandibular gland (e.g. inflammatory disease, infection, tumor). * Has a condition that precludes the safe performance of the skin punch biopsy procedure or may interfere with obtaining evaluable skin tissue biopsies, including any previous or active significant dermatological disease (e.g. previous biopsy with any of the following findings: inflammatory disease, scar tissue, psoriasis, keloid formation, skin cancer). * Any other medical or psychiatric condition or laboratory abnormality, which in the opinion of the Site Investigator would preclude participation. * Use of investigational drugs or devices within 30 days prior to the screening visit. Exclusion criteria (PD subjects): * Has other significant neurological disorders (clinically significant stroke, brain tumor, hydrocephalus, epilepsy, other neurodegenerative disorders, encephalitis, repeated head trauma, polyneuropathy). * Has significant autonomic dysfunction (symptomatic orthostasis, hypotension or urinary incontinence) suggestive of an atypical parkinsonism. * Has atypical features of parkinsonism including but not limited to supranuclear gaze palsy, early recurrent falls, corticospinal track abnormalities, cerebellar abnormalities, significant cognitive dysfunction. Exclusion criteria (HC subjects): * Has a family history of PD in any first-degree relative. * Has a significant neurological disorder (a neurodegenerative condition, clinically significant stroke, brain tumor, hydrocephalus, epilepsy, other neurodegenerative disorders, encephalitis, repeated head trauma, polyneuropathy). * Has a Montreal Cognitive Assessment (MoCA) score of less than 26. * Has a diagnosis of REM sleep behavior disorder. * Has a primary dystonia, restless legs syndrome, essential tremor, or other movement disorder.