A Clue Beneath the Skin

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Posted October 13, 2013
(from left): Ningshan Wang, Roy Freeman and Christopher Gibbons. Image: James Dwyer, Beth Israel Deaconess Media Services

(from left): Ningshan Wang, Roy Freeman and Christopher Gibbons. Image: James Dwyer, Beth Israel Deaconess Media Services

Study identifies possible biomarker for Parkinson’s disease

Although Parkinson’s disease is the second most prevalent neurodegenerative disorder in the United States, there are no standard clinical tests available to identify it. As a result, Parkinson’s disease often goes unrecognized until late in its progression, when the brain’s affected neurons have already been destroyed and telltale motor symptoms such as tremor and rigidity have already appeared.

Now, researchers from Harvard Medical School and Beth Israel Deaconess Medical Center have discovered that an important clue to diagnosing Parkinson’s may lie just beneath the skin.

In a study published online and scheduled to appear in the October 29 print issue of the journal Neurology, the investigators report that elevated levels of a protein called alpha-synuclein can be detected in the skin of people with Parkinson’s disease—findings that offer a possible biomarker to enable clinicians to identify and diagnose Parkinson’s before the disease has reached an advanced stage.

Parkinson’s disease affects more than 1 million people throughout the U.S. Diagnosis is currently made through neurological history and examination, often by a patient’s primary care physician.

“Even the experts are wrong in diagnosing Parkinson’s disease a large percentage of the time,” said senior author Roy Freeman, HMS professor of neurology and director of the Autonomic and Peripheral Nerve Laboratory at Beth Israel Deaconess. “A reliable biomarker could help doctors in more accurately diagnosing Parkinson’s disease at an earlier stage and thereby offer patients therapies before the disease has progressed.”

Alpha-synuclein is a protein found throughout the nervous system. Although its function is unknown, it is the primary component of protein clumps known as Lewy bodies, which are considered the hallmark of Parkinson’s disease. There is accumulating evidence that the protein plays a role in Parkinson’s disease development.

“Alpha-synuclein deposition occurs early in the course of Parkinson’s disease and precedes the onset of clinical symptoms,” explained Freeman, who with his coauthors suspected that the protein was elevated in the skin’s structures with autonomic innervation.

“Symptoms related to the autonomic nervous system, including changes in bowel function, temperature regulation and blood pressure control, may antedate motor symptoms in Parkinson’s patients,” he explained. “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 Parkinson’s biomarker.”

The research team enrolled 20 patients with Parkinson’s disease and 14 age- and sex-matched control subjects. The participants underwent examinations, autonomic testing and skin biopsies in three locations on the leg. Alpha-synuclein deposition and density of cutaneous sensory, sudomotor and pilomotor nerve fibers were measured.

As predicted, their results showed that alpha-synuclein was increased in the cutaneous nerves supplying the sweat glands and pilomotor muscles in the Parkinson’s patients. 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.

“There is a strong and unmet need for a biomarker for Parkinson’s disease,” said Freeman. “Alpha-synuclein deposition within the skin has the potential to provide a safe, accessible and repeatable biomarker. Our next steps will be to test whether this protein is present in the cutaneous nerves of individuals at risk for Parkinson’s disease, and whether measurement of alpha-synuclein deposition in the skin can differentiate Parkinson’s disease from other neurodegenerative disorders.”

Source: HMS

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