Parkinson’s Biomarkers

Discover how biomarkers can expand what we know about Parkinson’s disease (PD) and how biomarkers can possibly lead to earlier diagnosis.

What is a biomarker?

Biological markers (also known as biomarkers) are substances in the body that can give researchers and doctors information about a person’s health. For example, high cholesterol is a biomarker of heart disease. Biomarkers can be found in body tissues or fluids, such as blood or urine. We are currently in the beginning stages of using biomarkers to help diagnose Parkinson’s.

Why are biomarkers important in Parkinson’s?

There is no single test that your doctor can use to diagnose Parkinson’s. Instead, they rely on your present and past symptoms, your medical history and in-office exams to inform a diagnosis. In some cases, blood testing or other diagnostic tools — such as a dopamine transporter (DaT) scan, a skin biopsy or magnetic resonance imaging (MRI) of the brain — can support a diagnosis.

Researchers believe biomarkers not only hold the possibility to diagnose PD earlier and with greater precision, but that biomarkers may be a way to track disease progression and whether someone is responding to treatment. Finally, biomarkers can also help improve how we design clinical trials.

Alpha-synuclein

In Parkinson’s, alpha-synuclein is the first widely used biomarker to be applied in early clinical research. Alpha-synuclein is central to Parkinson’s — as it is a brain protein directly tied to cell loss in the brain.  

The normal human brain is rich with alpha-synuclein. It can also be found in lesser amounts throughout the body. In Parkinson’s, researchers believe that damaged alpha-synuclein folds into an irregular shape. The alpha-synuclein may then acts as a “seed,” causing normal alpha-synuclein to form toxic clumps, known as Lewy bodies. Researchers think that this abnormal alpha-synuclein somehow may alter brain function.

Recent breakthroughs have paved the way for researchers to spot misfolded alpha-synuclein in the cerebrospinal fluid of people with PD. The method for detecting this abnormal protein is called an alpha-synuclein seed amplification assay (SAA).

Alpha-synuclein Seed Amplification Assay

Scientists believe the seed amplification assay could someday be an efficient way to identify Parkinson’s and similar diseases, possibly even years before symptoms appear. However, there are currently limitations. Although commercially available, the testing method is not yet widely standardized and not all scientists have achieved the same results.

While the SAA biomarker test detects misfolded alpha-synuclein, it cannot predict whether someone who has misfolded alpha-synuclein will develop PD. The test currently does not differentiate between the various types of synucleinopathy, and it may not identify all cases of Parkinson’s.  One example are people with the LRRK2 genetic variant of PD, which may be missed by this test.

Additionally, the test cannot track PD progression. Testing in some centers requires a lumbar puncture (also known as a spinal tap), which is a procedure that removes a small amount of cerebrospinal fluid.

Biomarker Research

Researchers funded by the Parkinson’s Foundation and other granting agencies are exploring ways to redevelop the seed amplification assay to use serum or blood-based approaches rather than spinal fluid in testing. These tests thus have the potential to be easier on the patient and more accessible.

Scientists from Japan and Luxembourg recently published in the Nature medical journal a blood-based approach to measure alpha synuclein.

Researchers are also working on finding other Parkinson’s biomarkers (through skin biopsy, MRI and more) that can be used to detect the disease and possibly monitor its progression. (See Biomarkers in Parkinson’s disease: A state of the art review).

The Syn-One (Skin Biopsy) Test

The Syn-One Test® uses a skin sample to confirm the presence of synuclein in the nerves. The test works by identifying whether synuclein has undergone phosphorylation. Test results can potentially help PD doctors confirm a Parkinson’s diagnosis. 

For this test, a physician (not always your PD doctor), will perform three tiny skin biopsies on the upper back, lower thigh and lower leg. The areas are numbed with a local anesthetic. Results take about two to three weeks to be delivered to your doctor.

CND Life Sciences manufactures this test, processes the tests and states that Medicare possibly covers the cost of the test when appropriately ordered.

How does the test work?

The hallmark protein associated with Parkinson’s is called alpha-synuclein. Phosphorylation is an important biological process that helps cells regulate storage and energy. In a person with PD, phosphorylated alpha-synuclein may be present in nerves throughout the body and it can deposit in the nerve fibers of the skin. The Syn-One Test detects the presence of these abnormalities.

The test only confirms an abnormality is present, and cannot distinguish between Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy or REM sleep behavior disorder. Therefore, a doctor uses the test results alongside other tests to confirm a Parkinson’s diagnosis.

Does everyone need an alpha-synuclein seed amplification assay, a DaT scan or a Syn-One Test?

The short answer is no. Parkinson’s disease is diagnosed using the combination of a neurological examination, response to dopamine therapies and multiple follow-up visits. The seeding assay and the Syn-One Test alone cannot diagnose Parkinson’s. These tests are best used when it is questionable if a person has a synucleinopathy, however, it will not distinguish between them. The tests may not necessarily change treatment. 

Additionally, a doctor may order a DaT scan instead of an alpha-synuclein seed amplification assay or a Syn-One Test. Similarly, a DaT scan does not differentiate between the various forms of parkinsonism. Usually, if a doctor orders a test to help confirm a Parkinson’s diagnosis, either the skin biopsy test or DaT scan is chosen — not both.

The alpha-synuclein seed amplification assay is used for research and not available for your doctor to order.

Page reviewed by Dr. Michael S. Okun, Chair of Neurology and Executive Director at the Norman Fixel Institute for Neurological Diseases at the University of Florida Health and Dr. Lauren Fanty, Movement Disorders Fellow at the University of Florida, a Parkinson’s Foundation Center of Excellence.