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Cutaneous Alpha-Synuclein Deposition — A Biomarker in Parkinson’s Disease

There is an unmet need for a biomarker in Parkinson’s disease (PD). Accumulating evidence suggests that deposition of alpha-synuclein, the pathological hallmark of PD, occurs early in the course of the disease and may predate the appearance of the clinical features of the disease. Skin punch biopsy could provide a simple means to measure alpha-synuclein deposition in the peripheral nervous system. Because PD has prominent manifestations in the autonomic system (which controls visceral functions like digestion, heart rate, etc.), some of which antedate the motor manifestation of the disease, we hypothesized that alpha-synuclein deposition would be elevated in cutaneous (skin) structures with autonomic nerves. We therefore propose to measure alpha-synuclein deposition in the peripheral cutaneous autonomic nerves in a skin punch biopsy.

Project Description:
In the proposed studies we will determine the amount of phosphorylated alpha-synuclein in cutaneous autonomic of PD patients and controls. We will quantify alpha-synuclein deposition in the nerves to sweat glands, skin hair (piloarrector) muscles and blood vessels in tissue obtained (1) by skin punch biopsy from clinically diagnosed PD subjects and controls and (2) from post-mortem skin tissue of pathologically confirmed PD patients and controls.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:                     
A reliable biomarker could contribute to the diagnosis, treatment and disease modification of PD by: (1) improving diagnostic accuracy; (2) increasing cohort homogeneity in clinical trials; and (3) promoting early diagnosis, ideally in the pre-motor state.

Anticipated Outcome:          
We anticipate that measures of alpha-synuclein immunoreactivity in the skin will correlate with neuropathological scores and United Parkinson’s Disease Rating Scale scores.


  • Roy Freeman, MD

    Boston, MA United States

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