The primary objective of this study is to obtain detailed clinical information and biologic specimens from subjects with PD toward the ultimate end of identifying a biomarker of PD. Because of the inherent difficulties of using clinical outcome measures to assess disease modification, the identification of biomarkers of PD is of paramount importance. The ideal PD biomarker would be one that is easily assayed in a convenient biological sample, varies proportionally with disease severity, is abnormal during the pre-symptomatic phase of the illness, and is unaffected by drugs or other interventions used to treat PD. The existence of a sensitive biomarker with these properties would enable much more effective disease modifying research that would likely be able to take advantage of smaller and potentially shorter trials.

Subjects will be asked to attend study visits every 6 months for up to 5 years of follow up. Each visit will consist of patient outcomes questionnaires, neurological exams, computerized assessments of gait and balance, a video recorded motor exam, and biological specimen collection for biomarker discovery.

Inclusion Criteria:

• A diagnosis of idiopathic PD meeting UK PD Society Brain Bank Criteria (Step 1, Step 2, and 2 items present from step 3).1
• Male or female age 30 years or older at time of PD diagnosis, Hoehn & Yahr (H&Y) stage I-IV.
• Confirmation from I-123 Ioflupane SPECT (DatScan®) of dopamine transporter deficit for de-novo, untreated patients.
• Clinical evidence of response to dopaminergic medication (MAO-B inhibitors, dopamine agonists, levodopa, or combinations) in patients on treatment for PD.
• Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations.
• Able to make visits to UT Southwestern every 6 months for up to 5 years without undue hardship.

Exclusion Criteria:

• Idiopathic PD, H&Y stage 5, as these will be unable to participate in gait assessments.
• Confirmed or suspected atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis, or degenerative diseases.
• Presence of definite dementia (MoCA < 17)2.
• For de-novo subjects: received any of the following drugs that might interfere with dopamine transporter SPECT imaging: neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of screening.
• For the prospective CSF cohort: current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
• For the prospective CSF cohort: any condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or known clinically significant coagulopathy or thrombocytopenia.
• Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.

(1) de-novo, previously untreated patients within 5 years of symptom onset, n=20, and (2) patients on treatment with and clinically responsive to MAO-B inhibitors, dopamine agonists, amantadine, or levodopa (or combinations), n=220 and (3) healthy control patients without evidence of degenerative nerological disease.