Misfolded Proteins in the Skin of People With Parkinson's Disease and Other Parkinsonism

Assessing Skin Biomarkers for Preclinical Diagnosis of PD and Non-PD Parkinsonism

The purpose of this study is to determine whether identification of misfolded proteins in the skin will help to determine what sort of parkinsonism someone has. We seek to demonstrate whether someone has a synucleinopathy such as Parkinson's disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies(DLB), as opposed to a tauopathy such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) or no parkinsonism at all (control).

This is a clinical research study for patients with parkinsonism, including Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. Parkinsonism can be difficult to diagnose, especially in the early stages of the disease. Skin punch biopsy could be a useful and way to diagnose and measure the severity of these conditions. Given that there currently is no proven way to determine that someone has a synucleinopathy such as PD and not a tauopathy, this is a novel study that may lead to better ways to diagnose people with parkinsonism. The purpose of the study is to identify changes on a skin punch biopsy, in which small samples of skin are removed and sent to the laboratory for examination. We are seeking to measure the amount of misfolded alpha-synuclein in someone's skin. Participation will last between 1 and 2 years and will involve between 2 and 4 visits. Visits will include a physical examination, questionnaires, a memory test, blood draws and saliva collection, and a single visit for skin punch biopsies. We will also be looking to enroll volunteers to serve as "controls," who do not have any neurological illness.

Inclusion Criteria:

• Age 21 years old and age <90 years of age at the time of the baseline visit 1
• Age of diagnosis at least 40 years old for PD, DLB, and PSP and at least 30 years old for MSA
• A confirmed diagnosis of PD, PSP, CBD, MSA, DLB, or healthy control
• Montreal Cognitive Assessment (MoCA) > 10 at the outset of the study

Exclusion Criteria:

• Age 90 or above
• Allergy to local anesthetic
• History of deep brain stimulation (DBS) or other brain surgery prior to Visit 1
• For PD or DLB diagnoses, any other neurodegenerative or central nervous system process that would interfere with examination
• For PD or DLB, history of negative DATscan
• Use of investigational drugs or devices within 60 days prior to baseline visit (except for dietary supplements)
• In control subjects, family history of a neurodegenerative disease in a first degree or second degree blood relative
• History of schizophrenia
• History of antipsychotic medication use or exposure in controls or history of antipsychotic medication leading to parkinsonism (drug induced parkinsonism) in the parkinsonism group
• Blood clotting disorder
• On multiple (more than one) antiplatelet and/or anticoagulant blood thinner medications in combination (except for aspirin if it can be safely held for 1 week)
• Any other medical, psychiatric, or cognitive illness that in the investigator's opinion would interfere with cooperation or ability to undergo the study procedures.