Parkinson's disease clue may lie just under the skin

Date: Oct-08-2013By discovering that a nervous system protein tends to accumulate at a higher level just under the skin in patients with
Parkinson's disease, researchers believe they may have revealed an important clue to diagnosing Parkinson's disease.
Despite being the most frequently occurring neurodegenerative disease in the US, where it affects over 1 million people, Parkinson's
disease is difficult to diagnose: there are no standard clinical tests.

This means the disease is often diagnosed only when symptoms
like tremors and rigidity emerge, which is well after many brain cells have been destroyed.

Now a new study, published in a recent online issue of the journal Neurology, could help to change that.

Researchers from Beth Israel Deaconess Medical Center (BIDMC), a teaching hospital of Harvard Medical School, found that elevated
levels of a nervous system protein called alpha-synuclein can be detected in the skin of people with Parkinson's disease.

They suggest the protein could serve as a biomarker of the disease, helping to spot it before symptoms emerge, when it is hard to
detect with current methods.

Senior author Roy Freeman, professor of Neurology at Harvard Medical School and director of the Autonomic and Peripheral Nerve
Laboratory at BIDMC, says even experts are often wrong in diagnosing Parkinson's disease:

"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."
Main component of abnormal protein clumps in brain cells

Alpha-synuclein occurs throughout the nervous system, and although we do not know much about what it does, scientists have found it
is the main component of the abnormal clumps of protein or Lewy bodies, that form inside the brain cells of people with Parkinson's
disease. There is also growing evidence to suggest the protein plays a key role in the development of the disease.

Prof. Freeman says:

"Alpha-synuclein deposition occurs early in the course of Parkinson's disease and precedes the onset of clinical symptoms."
Signs of the protein accumulating around nerves in the skin

The researchers had a hunch that they might find earlier signs of Parkinson's by looking at the autonomic nervous system in the
skin, and at alpha-synuclein, in particular.

There is already a view that symptoms connected to the autonomic nervous system, such as changes in temperature and blood pressure
regulation, and bowel function, may precede the motor system symptoms seen in people with Parkinson's.

Autonomic nervous system changes also occur in the skin, such as excessive or diminished sweating, changes in skin color and
temperature. These symptoms occur in nearly two-thirds of patients with Parkinson's disease (PD), says Prof. Freeman.

"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 biomarker," he adds.
Higher levels of alpha-synuclein in skin structures of Parkinson's patients

They took their ideas into a study of 20 patients with Parkinson's disease and 14 controls matched for age and gender.

The participants underwent exams and tests of the autonomic nervous system. To measure alpha-synuclein levels, and density of
nerve fibers, the participants had skin biopsies on the leg.

The researchers found their hunch was right: the Parkinson's patients had higher levels of alpha-synuclein in the skin nerves
supplying the sweat glands and the pilomotor muscles (the ones that produce goose bumps).

They found higher levels of alpha-synuclein in the autonomic nerves of the skin were linked to more advanced Parkinson's symptoms
and worse functioning of the autonomic nervous system.

Freeman says there is a strong and unmet need for a biomarker for Parkinson's disease, and:

"Alpha-synuclein deposition within the skin has the potential to provide a safe, accessible and repeatable biomarker."

The researchers now plan to find out if the protein accumulates in the skin nerves of people at risk for Parkinson's disease, and
also if testing for it can distinguish Parkinson's from other neurodegenerative diseases.

Earlier this year, researchers at the Mayo Clinic in the US proposed a saliva test for Parkinson's disease.

Written by Catharine Paddock PhD

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