Could Skin Punch Biopsy Help Early Detection of Parkinson’s and Other Diseases?

Dr. Todd Levine’s father-in-law had lived with neurological symptoms for more than 10 years. REM-sleep behavior disorder (RBD) caused him to physically act out his dreams while he slept, as well as produced problems with his gait and regulating his blood pressure. 

Since these symptoms are risk factors for developing a handful of neurodegenerative diseases — Parkinson’s, dementia with Lewy bodies, and multiple system atrophy — Levine was concerned when the symptoms began to progress. 

In 2025, Levine flew his father-in-law from Toronto to visit him in Phoenix. Levine had spent his career developing skin punch tests that could help spot these diseases early. As chief medical officer of CND Life Sciences, he administered the Syn-One test that he helped develop to his father-in-law — which takes three 3mm samples of skin from the neck, near the knee, and ankle — and sent the results to his neurologists. 

Based on the clinical symptoms and results of the Syn-One test, the neurologists diagnosed with multiple system atrophy, allowing them time to search for clinical trials that he may be eligible for while in the earlier stages of the disease. 

The Syn-One test spots misfolded forms of the alpha-synuclein protein in the peripheral nerves near the skin. A positive test, in conjunction with a clinical assessment and medical history, could help diagnose neurodegenerative conditions where these misfolded proteins are driving neurodegeneration. 

The test provides “a window into the central nervous system,” Levine told Being Patient. “You don’t have to do an autopsy of the brain, you can actually see these changes occurring in living people.”

Alpha-synuclein: A key player across multiple neurodegenerative diseases

The alpha-synuclein is a protein made by nerve cells throughout the brain, spinal cord, and periphery. Its exact role is unclear, but when it is chemically modified through a process called phosphorylation, it begins to misfold. Misfolded forms of this protein are linked to several different neurological diseases — including Parkinson’s. The misfolding might start in peripheral nerves outside the brain in the earliest stages of these diseases, opening the door for early detection.

“A disease like Parkinson’s is not just a brain disease, and we have known that for a very long time,” said Levine. He called it a systemic disease since it also leads to constipation, sleep disorders, and other nerve problems which may stem from the accumulation of abnormal alpha-synuclein. 

Many people with Alzheimer’s also have alpha-synuclein build-up in the brain alongside beta-amyloid and tau. Some studies have linked alpha-synuclein in Alzheimer’s to faster cognitive decline.

Experts still urge caution around these tests. There are questions about alpha-synuclein as a diagnostic marker in the early stages of the disease, Dr. Holly Shill, medical director of the Muhammad Ali Parkinson Center at Barrow Neurological Institute, who is not involved in the development of the Syn-One test, told Being Patient.

“This aspect is critical,” she said, “as it is not at all clear that if you have a positive test, does that mean you have Parkinson’s now or does it mean that you have the pathology only and it may never progress into a clinical syndrome over one’s lifetime.”

There are no validated tests that measure alpha-synuclein in the living brain. The gold-standard test involves an autopsy. 

For now, neurologists turn to proxy measures: Cerebrospinal fluid tests that look for abnormal, clumping forms of alpha-synuclein called seeding assays and the Syn-One test. Though they are commonly used by neurologists, “they are not yet considered part of standard of care,” said Shill. 

Not everyone diagnosed with Parkinson’s, for example, will test positive on a cerebrospinal fluid alpha-synuclein test.

While scientists developed blood tests to measure the presence of misfolded proteins in Alzheimer’s disease, it hasn’t worked yet for alpha-synuclein. “There is a lot of alpha-synuclein in platelets and red blood cells,” said Levine. “If you have this massive sea of alpha-synuclein in your blood, detecting a very small change [due to disease-related accumulation] has not proven to be very feasible.” 

Skin biopsy tests in action

The Syn-One test was launched in 2019. Levine said that the Syn-One test is used by more than 3,500 neurologists in the U.S., including specialist centers that rely on it to aid diagnoses in complex cases, and is covered by Medicare. “Skin biopsy is used far more frequently as it is easier to integrate it into the clinic compared to spinal fluid analysis,” said Shill.

While a trial conducted by the company found the test agreed with an expert clinical assessment 92 percent of the time, a smaller study by outside researchers found that only 60 percent of people clinically diagnosed with dementia with Lewy bodies tested positive via this test. Two other company-led studies found that the test altered clinical care and diagnosis more than 60 percent of the time.

Levine and other researchers affiliated with CND Life Sciences were among the 5,500 attendees at the 2026 AD/PD Alzheimer’s Disease and Parkinson’s Disease Conference in Copenhagen, which showcases the latest data from trials, biomarker studies, and other research into neurodegenerative disease. At the conference, CND Life Sciences shared more data strengthening the case for the Syn-One test. 

One study of 108 participants showed that the levels of alpha-synuclein increases as dementia with Lewy bodies progresses over the course of six months. The test could be used to track the effectiveness of experimental treatments that lower alpha-synuclein levels. A smaller study of 58 participants showed that the Syn-One test could detect abnormal alpha-synuclein across RBD and in all stages of Parkinson’s — though it only looked at six people with RBD and five with early stage Parkinson’s.

Still Shill, cautioned that skin punch alpha-synuclein tests aren’t validated against an autopsy, the gold standard for detecting the biomarker. Neither are currently approved by the FDA and the tests “have not had true independent validation by third party entities to ensure their accuracy” which “hamper our trust and reliance,” she said.

Nonetheless, some drug trials are already using the Syn-One test to enrich their studies with participants who are positive for alpha-synuclein. Ultimately, Levine hopes that the test might prove accurate enough to one day predict who might develop Parkinson’s or other neurodegenerative diseases, and help them get treated or enrolled into trials earlier.