The Harvard Biomarker Study is a Harvard-wide, longitudinal case-control study designed for discovering, replicating, and developing biomarkers for Parkinson's disease and Alzheimer's disease. High-quality biosamples and high-resolution clinical phenotypes are tracked at three visits over a two-year period for more than 2,000 individuals with early-stage PD, MCI/AD, and controls without neurologic disease.

The present "Ancillary Longitudinal CSF Collection Study (short HBS2)" is an ancillary study to the parent Harvard Biomarker Study. HBS2 is funded by the NINDS. In HBS2, 75 participants are more intensely studied and followed over a three-year time period. Clinical data and blood biospecimens are collected every six months and four annual CSF collections are performed. Biospecimens and clinical data are deposited into the NINDS PD Biomarkers Program (PDBP) Repository and the Data Management Resource (DMR) and are accessible through the PDBP DMR website.

Inclusion Criteria for Cases with PD:

• Age ≥ 21
• UK Parkinson's Disease Society Brain Bank criteria or movement disorder specialist diagnosis of PD
• Hoehn & Yahr stage ≤ 3.0
• Mini Mental State Exam score >21 OR authorized legal guardian available to sign consent
• Able to provide informed consent

Inclusion Criteria for Controls:

• Age ≥ 21
• Absence of any neurological disease
• No family history of a first-degree relative with PD
• Mini Mental State Exam score >21 OR authorized legal guardian available to sign consent
• Able to provide informed consent

Exclusion Criteria for Cases and Controls:

• Acquired or inherited bleeding disorders
• Hematologic malignancies
• Hematocrit < 30
• Active ulcer or active colitis
• Known pregnancy
• Clinical contraindications to lumbar puncture (including: known mass lesion of the CNS or evidence for raised intracranial pressure on fundoscopic exam; abnormal coagulation tests; platelet count < 50,000; subject on warfarin (coumadin), heparin, dabigatran, rivaroxiban or apixaban; subject on both aspirin and clopidogrel (Plavix); infection near the LP site or spinal deformity; known allergy to lidocaine)

Two tertiary care centers.