The assay under investigation did not show evidence of accurately detecting alpha-synuclein in specimens collected in the study other than CSF and the intention of the study was to identify less invasive ways to measure alpha-synuclein.

This will be an observational study looking at clinical and biomarker characteristics in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid (CSF) samples will be collected from participants.

This is an observational study looking at clinical and biomarker characteristics in patients with Parkinson's disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus (NPH) and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid samples will be collected from participants. Samples will be assessed for levels of misfolded alpha-synuclein aggregates. Clinical characteristics will also be assessed.

Misfolded alpha-synuclein aggregates have the potential to serve as an early biomarker for PD and MSA, increasing the ability to diagnose and treat individuals with these diseases earlier. This study examines the effectiveness of using a novel technique for distinguishing between different parkinsonian disorders by measuring small misfolded α-synuclein aggregates in different biofluids.

For PD subjects:

Inclusion Criteria:

1. Age 50-75
2. Diagnosis of idiopathic PD as confirmed by a movement disorder specialist
3. Age of onset of motor symptoms between 50 - 75
4. Well-established response to dopaminergic agents and/or amantadine
5. Ability to complete questionnaires
6. Ability to provide informed consent
7. Willingness to go off parkinsonian medication for 12 hours prior to "off" assessment
8. Medical record includes a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria:

1. Symptomatic (secondary) parkinsonism (ie. drug induced)
2. Atypical parkinsonian variants
3. History of cancer (except basal or squamous cell skin cancer) within 5 years
4. Known liver disease
5. Hematological disorders
6. History of stereotactic or ablative brain surgery
7. Treatment with an investigational drug or device within the last 30 days
8. Pregnancy
9. Inability to comply with or tolerate study procedures
10. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

MSA Subjects:

Inclusion Criteria:

1. Age 50-75
2. Age of onset of motor symptoms between 50-75
3. Diagnosis of probable or possible MSA as confirmed by a movement disorders specialist
4. Ability to complete questionnaires
5. Ability to provide informed consent
6. Willingness to go off parkinsonian medications for 12 hours prior to "off" assessment
7. Medical record indicates a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria

1. Symptomatic (secondary) parkinsonism (ie. drug induced)
2. History of cancer (except basal or squamous cell skin cancer) within 5 years
3. Known liver disease
4. Hematological disorders
5. History of stereotactic or ablative brain surgery
6. Treatment with an investigational drug or device within the last 30 days
7. Pregnancy
8. Inability to comply with or tolerate study procedures
9. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For RBD Subjects:

Inclusion Criteria:

1. Age 50-75
2. Diagnosis of RBD using current consensus criteria
3. Ability to provide informed consent
4. Ability to complete questionnaires
5. Medical record indicates a brain MRI taken within the past 12 months showing no evidence of a tumor or abscess

Exclusion Criteria

1. Signs for symptoms suggestive of parkinsonian disorder
2. History of cancer (except basal or squamous cell skin cancer) within 5 years
3. Known liver disease
4. Hematological disorders
5. History of stereotactic or ablative brain surgery
6. Treatment with an investigational drug or device within the last 30 days
7. Pregnancy
8. Inability to comply with or tolerate study procedures
9. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For NPH:

Inclusion Criteria:

1. Age 50-75
2. Scheduled to undergo an LP to evaluate diagnosis of NPH at Stony Brook Neurological Associates
3. Ability to complete questionnaires
4. Ability to provide informed consent

Exclusion Criteria:

1. History of cancer (except basal or squamous cell skin cancer) within 5 years
2. Known liver disease
3. Hematological disorders
4. History of stereotactic or ablative brain surgery
5. Treatment with an investigational drug or device within the last 30 days
6. Pregnancy
7. Inability to comply with or tolerate study procedures
8. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

For Controls:

Inclusion Criteria:

1. Age 50-75
2. Scheduled to undergo an LP at Stony Brook Neurological Associates
3. Ability to complete questionnaires
4. Ability to provide informed consent

Exclusion Criteria:

1. Signs or symptoms suggestive of parkinsonian disorder
2. History of rapid eye movement (REM) Sleep Behavior Disorder (RBD)
3. History of cancer (except basal or squamous cell skin cancer) within 5 years
4. Known liver disease
5. Hematological disorders
6. History of stereotactic or ablative brain surgery
7. Treatment with an investigational drug or device within the last 30 days
8. Pregnancy
9. Inability to comply with or tolerate study procedures
10. Conditions precluding the safe performance of lumbar puncture (LP): use of anticoagulants and hematologic abnormalities (INR>1.3;platelet count <80,000)

Subjects with PD, MSA, RBD, NPH and controls

Identifiers will be removed from participant data or biospecimens. After such removal, the information or biospecimens may be used for future research studies.