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Ask the MD: A Skin Test for Parkinson’s

Trials Testing New Therapies for Parkinson's Symptoms

Editor’s note (March 21, 2024): This blog describes a skin test that detects the biology of Parkinson’s and related diseases, and, as such, is a valuable research tool. On March 20, 2024, researchers published data on the skin test in The Journal of the American Medical Association's (JAMA) Network.

Their results indicate that a high proportion of people who are diagnosed with Parkinson’s or related diseases have a positive skin test. Further research will help validate these findings and clarify the test’s role and benefit in clinical care. You can explore more in our blog on the publication.

Learn more about the skin test below and talk with a movement disorder specialist if you have questions about if and how this or similar tests might be helpful for you or your loved ones.


On the heels of a big breakthrough — a spinal fluid (CSF) test for Parkinson’s, or alpha-synuclein seed amplification assay (α-syn SAA in CSF) — comes yet another. Read about the spinal fluid test, enabled by MJFF’s Parkinson’s Progression Markers Initiative Study.

This time: A possible skin test for Parkinson’s disease (PD). Researchers recently shared results of a test that can, with high accuracy, identify abnormal protein in the skin. This protein — alpha-synuclein — is the hallmark of Parkinson’s and related disorders, like Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB). It’s a protein we all, disease or not, have. It helps nerves and other cells communicate. But in PD, alpha-synuclein changes shape, misfolds and clumps, clogging cells and impacting their ability to work. Previously, this misfolded protein could only be seen in the brain at autopsy. But with recent advances, researchers can now detect abnormal alpha-synuclein in both spinal fluid and skin. And ongoing work aims to measure the protein in blood and other tissues, like the lining of the nose and salivary gland, as well as to visualize it in the living brain.

Here, we discuss the skin test, how it compares to the spinal fluid test, and what’s next.

A skin test for Parkinson’s? Tell me more!

The test involves three small tissue samples (biopsies) from the skin of the neck, thigh and ankle. The tissue is sent to a lab, where it’s treated with a tool that stains, or highlights, abnormal alpha-synuclein. Doctors look for this highlighted protein using a microscope. They also look for other helpful information, such as how many nerve (feeling, or sensory) fibers are present and whether they’re damaged.  

What does the test tell?

The test tells whether, at the time it’s done, a person has abnormal alpha-synuclein in their skin. It can point, generally, toward or away from Parkinson’s and other diseases of alpha-synuclein, like MSA or DLB. It cannot yet, on its own or in a person without symptoms, diagnose or predict a specific disease. Your doctor must interpret the results in the context of your symptoms and physical examination to confirm or rule out a suspected disease. 

Does it change how doctors diagnose Parkinson’s?

The diagnosis of PD remains clinical — not based on a test, but on your medical history and an expert doctor’s examination. Only when a person has the cardinal motor symptoms of Parkinson’s — slowness plus tremor or stiffness — can a diagnosis be made. The test doesn’t change that yet. But soon, the skin test, like α-syn SAA in CSF and others in the pipeline, will, hopefully, transform how and when doctors can diagnose and care for disease.

These tests also give us the first glimpses of disease biology — what’s happening in the cells of people with PD — during life (vs. at autopsy). They’re also uncovering how and why symptoms and progression differ from person to person. These tests should lead to better understanding of the disease and, ultimately, toward more personalized treatment.

Should I get this test?

When considering any test, you should ask your doctor what it can and can’t tell, any risks, and, most importantly, if and how it will direct treatment, care or prognosis. If the results, either positive or negative, won’t affect what you and your doctor do, then it may not be worth the time and cost.

In someone with clear-cut Parkinson’s symptoms and response to PD meds, for example, the skin test (or α-syn SAA in CSF, for that matter) is unlikely to add much to what’s already known.

And, although work is ongoing, the test has not yet been fully studied in people at risk for PD or those living with early potential symptoms of PD, like REM sleep behavior disorder (RBD). So, at the current time, the test cannot predict Parkinson’s. It also wouldn’t change treatment as there aren’t yet proven therapies (outside of regular exercise and a healthy diet) to prevent disease. As more trials focus on prevention, though, this and other alpha-synuclein tests could increasingly inform research participation.

The bottom line: If you wonder about this test, talk with a movement disorder specialist, a doctor with expertise in PD and similar conditions. (Find a movement disorder specialist.) They can help you understand the pros and cons and, if you decide together to proceed, interpret your results. It’s also worth investigating any cost to you, as insurance coverage varies, ahead of time.

Will this test change research?

Like α-syn SAA in CSF, it already is! These tests help ensure “the right people get into the right trials.” Many trials are testing therapies against alpha-synuclein with the goal of slowing Parkinson’s disease change over time. These tests can confirm research volunteers have abnormal alpha-synuclein and, in doing so, give more confidence in results. If an alpha-synuclein drug study is negative, for example, researchers can be sure it’s because an intervention didn’t work. They aren’t left wondering if, perhaps, some participants didn’t have the protein of interest so the drug might not help, regardless.

Speaking of research, what’s the data on the skin test?

Many groups have published data on the detection of alpha-synuclein through skin biopsy. Historically, results have been mixed. This could be due to differences in methods, biopsy sites or interpretation.

More recently, the National Institutes of Health (NIH) supported a multicenter study evaluating skin biopsy in 428 people with PD and related disorders as well as 120 control volunteers. Results showed the test was very accurate. In scientific terms, it had an overall 95.5 percent sensitivity (positive in people diagnosed with disease) and 96.7 percent specificity (negative in people not diagnosed with disease). In those with Parkinson’s, sensitivity was 92.7 percent. The test was also well-tolerated with minimal side effects, such as bleeding. These results have not yet been published in a peer-reviewed journal but were presented at the April 2023 American Academy of Neurology annual meeting.

In parallel, the same investigators published in Neurology the results of a small study comparing people with PD, MSA and control volunteers. They reported a difference in the amount and distribution of alpha-synuclein across skin biopsies in people with MSA vs. PD. This suggests the test may be able to differentiate PD from MSA, which can look alike, especially early in disease. If larger studies confirm these results, this test may be a valuable tool for distinguishing these similar diseases. But it’s not quite ready for that type of widespread use.

While not directly involved in these recent studies, The Michael J. Fox Foundation has, since 2006, funded work to measure alpha-synuclein in different body tissues, including the skin, colon, blood and salivary (submandibular) gland. This includes support of early skin biopsy research in the laboratory of Roy Freeman, MD, who founded CND Life Sciences, which developed the available skin biopsy test.

What about the spinal fluid test? How is it similar or different?

α-syn SAA in CSF uses a different method to measure a different form of abnormal alpha-synuclein in spinal fluid. Through a lumbar puncture, or spinal tap, a small amount of spinal fluid is removed. In the lab, the fluid is mixed with a man-made abnormal alpha-synuclein protein. If there’s abnormal protein in the spinal fluid sample, it clumps up.

α-syn SAA in CSF was validated through MJFF’s Parkinson’s Progression Markers Initiative (PPMI). In a study published in Lancet Neurology of over 1100 people with PD, genetic links to PD, early potential signs of PD and control volunteers, α-syn SAA in CSF was very accurate at detecting abnormal alpha-synuclein. In people with PD and an abnormal DaTscan (a brain scan that shows loss of dopamine), sensitivity was 87.7 percent. This rose to 98.6 percent in people with PD, abnormal DaT and smell loss. Separate, smaller studies also suggest this test might distinguish PD from MSA, but as with the skin test, these results need larger validation.

Like the skin test, α-syn SAA in CSF can only tell whether protein is present at the time of the test. Also like the skin test, it gives a yes or no result. It can’t yet measure the amount or see if and how it’s changing with time. And, while α-syn SAA in CSF is positive in most people who have early potential signs of disease, like RBD and smell loss, it can’t yet predict who will develop PD. Ongoing work is investigating the skin test in these groups. (Read a blog and watch a webinar about α-syn SAA in CSF.)

What are the next steps?

For the skin test, the next steps are to gather confirmatory data in larger studies — to validate the test’s accuracy in bigger groups of people.  

For α-syn SAA, MJFF is supporting work on this test in skin and other tissues. And other ongoing work, some just published in Nature, is studying α-syn SAA in blood as well. (Stay tuned for more on those results!)

For any test, regardless of how and where it’s done, research now focuses on:

  • Evaluating test results against autopsy findings (the gold standard of disease diagnosis) through contributions of people who donate their brain for research
  • Finding the easiest, lowest risk but highest quality method of testing, such as a blood draw or nasal swab
  • Validating a tool to separate Parkinson’s from similar diseases, like MSA
  • Quantifying results: moving from yes/no or visual results to measurements that can be tracked over time, correlated with symptoms, and predictive of disease and/or progression

What’s the bottom line?

Like α-syn SAA in CSF, this is a promising development in the field. It has immediate and broad implications for research and more efficient clinical trial testing. And it will likely have widespread effects on diagnosis, care and prognosis of Parkinson’s and related disease in the future. For now, if you’re considering one of these tests, meet with a movement disorder specialist who can talk you through the pros, cons and limitations of today’s testing.  

And remember, these (and future) breakthroughs are not possible without you and your participation in research. Learn more about PPMI and join the study that’s changing everything.

We are grateful to Charles Adler, MD, PhD, consultant and professor of neurology and the Wayne and Kathryn Preisel Professor of Neuroscience Research at Mayo Clinic in Scottsdale, Arizona, for his input on and review of this material. Dr. Adler served as a research consultant and reviewer for CND Life Sciences, which developed the commercially available skin biopsy test.  

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