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Researchers from Beth Israel Deaconess Medical Center (BIDMC) report in the October 29th issue of the journal Neurology that elevated levels of the protein alpha-synuclein can be detected in the skin of Parkinson’s disease patients . The finding offers a potential biomarker to enable doctors to identify and diagnose Parkinson’s before the disease has reached an advanced stage.
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting approximately seven million people worldwide. Despite it’s prevalence, a clinical test to diagnose the disorder doesn’t exist, and consequently Parkinson’s often goes unrecognized until later in progression when it has destroyed neurons in the brain and caused motor symptoms.
Parkinson’s disease is characterized by the abnormal aggregation of the protein alpha-synuclein (SNCA) into clusters called Lewy bodies in neurons, and the loss of dopamine-producing neurons in the brain. Nerve cells use dopamine to help control muscle movement. The loss of dopmaine-producing neurons results in an insufficient level of dopamine and subsequent loss of muscle function. The damage gets worse with time, causing various motor symptoms: tremors, rigidity, slowness of movement, and/or loss of balance.
Alpha-synuclein deposition occurs early in the development of Parkinson’s disease prior to the onset of clinical symptoms. Symptoms related to the autonomic nervous system (also called the involuntary nervous system) may also precede motor symptoms in Parkinson’s patients, including changes in bowel function, temperature regulation and blood pressure control.
Roy Freeman, MD, Director of the Autonomic and Peripheral Nerve Laboratory at BIDMC, Professor of Neurology at Harvard Medical School, and senior author of the study explained why scientists went looking for a biomarker in nerves just below the skin :
Skin-related autonomic manifestations, including excessive and diminished sweating and changes in skin color and temperature, occur in almost two-thirds of patients with Parkinson’s disease. The skin can provide an accessible window to the nervous system and based on these clinical observations, we decided to test whether examination of the nerves in a skin biopsy could be used to identify a PD [Parkinson’s disease] biomarker.
Researchers evaluated 20 patients with Parkinson’s disease and 14 control subjects of similar age and gender. The scientists performed autonomic testing — tests that measure how the systems in the body that are controlled by the autonomic nerves respond to stimulation — and took skin biopsies from three locations on the leg to measure accumulation of alpha-synuclein and density of cutaneous nerve fibers.
Consistent with their hypothesis, scientists found more alpha-synuclein in the cutaneous nerves supplying the sweat glands and pilomotor muscles in the Parkinson’s patients compared to control subjects. Higher alpha-synuclein deposition in the nerves supplying the skin’s autonomic structures was associated with more advanced Parkinson’s disease and worsening autonomic function.
The researchers next plan to test whether the protein is present in the cutaneous nerves of people at risk for Parkinson’s disease, and whether the biomarker can differentiate Parkinson’s disease from other neurodegenerative disorders.
- Wang et al. alpha-Synuclein in cutaneous autonomic nerves. Neurology. 2013 Oct 29;81(18):1604-10. doi: 10.1212/WNL.0b013e3182a9f449. Epub 2013 Oct 2.
- BIDMC Researchers Identify Possible Biomarker for Parkinson’s Disease. Biomarker Commons. 2013 Nov 5.