A Simple Skin Test Can Detect Parkinson's and Other Brain Diseases

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A simple skin biopsy test that can be done at the doctor's office was effective in detecting Parkinson's disease with 93 percent accuracy, according to a new study published on March 20 in JAMA.

Although the special biopsy, called a Syn-One Test, has been shown to be effective in identifying different neurological disorders, this was the first to look at the subgroup of neurodegenerative conditions known collectively as synucleinopathies — including Parkinson's disease, Lewy body dementia, multiple system atrophy, and pure autonomic failure — in one large, blinded study that included multiple centers around the United States.

"Too often patients experience delays in diagnosis or are misdiagnosed due to the complexity of these diseases," says lead author Christopher Gibbons, MD, a neurologist at Beth Israel Deaconess Medical Center and a professor of neurology at Harvard Medical School in Boston. Being able to detect the abnormal protein that is seen in Parkinson's disease and related conditions with very high accuracy will allow for better diagnostic answers and improve care for patients, says Dr. Gibbons.

More Than 1 in 4 People Are Given an Incorrect Diagnosis Before Being Correctly Diagnosed With Parkinson's

Each year, an estimated 180,000 people in the United States are diagnosed with Parkinson's disease, Lewy body dementia, and related disorders, according to the authors. Although Parkinson's disease is the most well known of the synucleinopathies, Lewy body dementia is actually more common.

But because these conditions share some overlapping signs and symptoms, like tremors and cognitive changes, diagnosis can be challenging.

A 2020 survey conducted by Parkinson's UK found that 1 in 4 people reported they were misdiagnosed with a different condition before receiving the correct Parkinson's diagnosis.

Lewy body dementia can also be misdiagnosed because the cognitive symptoms (especially early in the disease course) can be similar to those of Alzheimer's disease. Distinguishing between the two is important — some medications used for Alzheimer's symptoms can cause serious side effects in people with Lewy body dementia.

Test Correctly Identified People With Neurodegenerative Diseases Between 93 and 100 Percent of Cases

Researchers from 30 academic and community-based neurology practices around the U.S. enrolled 428 people between ages 40 and 99: 151 healthy people without brain disease, and 277 people with a diagnosis of one of the four neurodegenerative diseases based on a physical exam and symptoms, and confirmed by an expert panel.

Participants underwent three 3-millimeter skin punch biopsies taken from the neck, the knee, and the ankle. The researchers were looking for an abnormal protein that is seen in the brain and spinal cord of people with synucleinopathies called phosphorylated a-synuclein, or P-SYN.

Key findings included:

• In people with clinically confirmed Parkinson's disease, 93 percent demonstrated a positive skin biopsy for P-SYN that confirmed the diagnosis.
• Participants with Lewy body dementia and multiple system atrophy tested positive 96 percent and 98 percent of the time, respectively.
• A full 100 percent of people with pure autonomic failure were positive for the abnormal protein.

In the control group, just over 3 percent had biopsies that tested positive for P-SYN — an error rate the authors suspect may indicate some of the healthy controls are at risk for one of the conditions because the protein can be present in the skin even in the earliest stages of the diseases.

The fact that almost no skin samples from healthy people had aggregates of P-SYN, and the vast majority of samples from patients did, suggests that the skin might offer a window to see what is happening in the brain, says Rizwan Akhtar, MD, PhD, an assistant professor neurology at Northwestern Medicine in Chicago.

How Can a Simple Skin Biopsy Detect a Brain Disease?

It's thought that many of the neurodegenerative diseases are caused by clumps of proteins that form inside and around brain cells, causing problems with how cells function, Dr. Akhtar explains.

Because we cannot directly see these clumps in the brain when a person is still living, many scientists have been working to find a biomarker that could indicate the presence of the disease in another part or fluid in the body, he explains. Although not involved in this study, Akhtar oversees several clinical trials looking for biomarkers of neurodegenerative diseases in body fluids.

The seeds of this breakthrough were first planted in 2009 when researchers discovered that Parkinson's disease disrupts the peripheral nerves (nerves outside the brain and spinal cord, including in the skin) that are linked to many of the non-motor symptoms of the disease, such as constipation and problems with blood pressure control or urination.

Researchers hypothesized that P-SYN might be found in peripheral nerves in the skin as well.

Skin Biopsy Test Could Be Used to Help Develop Better Treatments

Not only can the test be used to better diagnose and treat people, but researchers also hope it will lead to better treatments for these diseases.

Finding new treatments for conditions like Parkinson's disease is very challenging, and using the test to identify people very early in the disease course before they are enrolled in the trial can confirm that they actually have one of the four diseases.

Right now the biopsy test cannot distinguish between these conditions, but the hope is that it can be refined over time to do so, says Akhtar.

"In addition, being able to measure the amount of protein in the nerves is critical if you are hoping that a new therapy is going to be able to reduce this protein," says Gibbons. Researchers hope that the test could be repeated over time to look for a change in the amount of this protein, but it hasn't been confirmed that the test will predict disease changes over time.

The Skin Test for Parkinson's Disease and Other Neurodegenerative Disease Is Available — But Who Should Get It?

The Syn-One Test has been available since 2020, and over 1,000 neurologists throughout the United States are using it, says Gibbons.

"In general, this test is most useful to help clarify a particular diagnosis — for example, does a person have Parkinson's disease or is this parkinsonism induced by a medication," he says. In that example, the latter would not have the abnormal protein.

"It can be used for people who have symptoms that are not exactly diagnostic for Parkinson's disease, where the physician is not sure. We are doing two additional studies that look at much earlier stages of disease to see if we can make a diagnosis before all the symptoms are present, and we anticipate those results over the next year or so," says Gibbons.

Several of the authors own stock in the copy that manufactures the tests, CND Life Sciences.