A minimally invasive test offering a potential window into the earliest stages of neurodegenerative diseases like Parkinson’s and dementia with Lewy bodies is gaining traction among neurologists. The test, known as Syn-One, analyzes a small skin sample for misfolded alpha-synuclein, a protein increasingly linked to these conditions. Recent data presented at the 2026 AD/PD Alzheimer’s Disease and Parkinson’s Disease Conference in Copenhagen further strengthens the case for its use in diagnosis and clinical trial enrollment.
The development of this test is deeply personal for Dr. Todd Levine, chief medical officer of CND Life Sciences. His father-in-law’s decade-long struggle with neurological symptoms – including REM-sleep behavior disorder, gait problems, and blood pressure regulation issues – prompted Levine to accelerate his research into early detection methods. These symptoms are known risk factors for Parkinson’s, dementia with Lewy bodies, and multiple system atrophy, highlighting the urgency for timely diagnosis.
In 2025, Levine administered the Syn-One test to his father-in-law after flying him from Toronto to Phoenix. The test involves taking three small, 3mm skin samples from the neck, knee, and ankle. Analysis of these samples revealed the presence of misfolded alpha-synuclein, contributing to a diagnosis of multiple system atrophy and allowing the family to explore potential clinical trial options.
How the Skin Biopsy Works
The Syn-One test identifies abnormal forms of the alpha-synuclein protein in peripheral nerves near the skin’s surface. Researchers believe that the misfolding of this protein may start in these peripheral nerves long before symptoms manifest in the brain, offering a crucial opportunity for early detection. “You don’t have to do an autopsy of the brain, you can actually see these changes occurring in living people,” Levine explained, describing the test as providing “a window into the central nervous system.”
Alpha-synuclein is a protein found throughout the nervous system, but its precise function remains unclear. When chemically modified through phosphorylation, it can misfold and accumulate, contributing to the development of several neurodegenerative diseases, including Parkinson’s. Interestingly, research suggests that Parkinson’s isn’t solely a brain disease, but a systemic one, with alpha-synuclein accumulation potentially contributing to issues like constipation and sleep disorders. Alpha-synuclein buildup has also been observed in some individuals with Alzheimer’s disease, potentially accelerating cognitive decline.
Cautious Optimism and Ongoing Research
While the Syn-One test shows promise, experts caution against relying on it as a definitive diagnostic tool at this stage. Dr. Holly Shill, medical director of the Muhammad Ali Parkinson Center at Barrow Neurological Institute, emphasized the need for further research to determine the significance of a positive test result. “This aspect is critical,” she said, “as it is not at all clear that if you have a positive test, does that signify 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.”
Currently, the gold standard for confirming the presence of alpha-synuclein pathology remains an autopsy. Neurologists currently rely on proxy measures like cerebrospinal fluid tests and the Syn-One test, but these are not yet considered standard of care. While cerebrospinal fluid tests can detect abnormal alpha-synuclein, they are more invasive than a skin biopsy. Blood tests for alpha-synuclein have proven challenging due to the high concentration of the protein in blood cells, making it difficult to detect subtle changes related to disease.
Clinical Use and Future Directions
Launched in 2019, the Syn-One test is now used by over 3,500 neurologists in the United States, including specialist centers. It is also covered by Medicare. Studies have shown varying degrees of accuracy, with one company-led trial reporting 92% agreement with expert clinical assessment, while an independent study found a 60% positive rate in patients diagnosed with dementia with Lewy bodies. Recent research presented at the AD/PD conference indicated that alpha-synuclein levels detected by the test correlate with the progression of dementia with Lewy bodies over six months and can detect abnormalities across a range of Parkinson’s-related conditions.
Despite these advancements, Dr. Shill cautions that the test hasn’t been validated against autopsy results and lacks independent verification to ensure accuracy. But, the Syn-One test is already being utilized in some drug trials to identify participants with confirmed alpha-synuclein pathology, potentially accelerating the development of new therapies. Levine and his colleagues hope that continued research will refine the test’s accuracy, ultimately enabling earlier prediction and treatment of Parkinson’s and other neurodegenerative diseases.
Disclaimer: This article provides informational content and should not be considered medical advice. Please consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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