Biomarkers for Parkinson ‘s — explained

One of the major challenges for developing better treatments is the lack of a simple test to diagnose and monitor Parkinson’s progression. But, could we be on the verge of a breakthrough?

What is a biomarker?

  • A biomarker is a measurable change in the body that can tell us something about the presence or severity of a condition. A test that measures this change can be used to diagnose and monitor a condition.
  • We don’t currently have a test like this for Parkinson’s, but researchers are working hard to find one.
  • Candidates include tests that analyse blood, breath and cerebrospinal fluid.
  • You can help speed up the search for biomarkers by taking part in research.

How is Parkinson’s diagnosed?

In medicine today, a simple blood test or scan can detect a variety of conditions, including some which have only been known about for a few decades. But when it comes to Parkinson's, a condition that was first described over 200 years ago, there is still no definitive diagnostic test. This means confirming someone has Parkinson’s can take some time. And, as there are other conditions with similar symptoms — like other types of tremor and Parkinsonisms — sometimes the wrong diagnosis can be given. Some studies suggest that the rate of misdiagnosis is as high as 20–30% in the early stages, and even in the latest stages clinical diagnosis is around 85% accurate.

One test that can be used in the diagnosis of Parkinson’s is a type of brain scan known as a DaTscan. The scan gets it’s name from what it is measuring in the brain — the dopamine transporter protein.

The DaTscan works by lighting up the transporter protein using low levels of a radioactive marker that shows where this protein is when the brain is scanned. The transporter protein has an important role to recycle dopamine that has been pumped out of the dopamine producing cells. But in Parkinson’s, as these cells are lost, the levels of the transporter protein is reduced.

So, a DaTscan works as an indirect assessment of the number of dopamine producing brain cells left in the substantia nigra. And, while this test is not a definitive diagnostic test, it can be used when clinicians are uncertain what the condition may be — if a person with Parkinson’s like symptoms has normal levels of the transporter it could indicate a different diagnosis. And researchers believe that using the test could help to improve clinical trials of drugs that have the potential to slow the condition. You can read more about this here:

But today, when it comes to diagnosing Parkinson’s, ultimately it is up to the skill of a specialist to look for common signs of the condition, while also looking for any other signs that may suggest a different diagnosis. But, even in the later stages of the condition, clinical diagnosis is only around 85% accurate.

Challenges beyond detection

It is not just detection that is challenging. The same lack of a simple test for the condition also means we cannot accurately measure its progression or predict how individuals will respond to different therapies. What is more, the absence of these tests is hampering efforts to develop new and better treatments that do more than simply mask symptoms. For example, without an effective measure of how fast Parkinson’s is progressing, demonstrating that a drug can slow progression in a clinical trial becomes very tricky indeed. You can read more about the importance of choosing the right measures in this post:

So to develop better treatments and improve diagnosis, it is clear that improvements in the way we measure Parkinson’s would be hugely helpful, if not essential.

Criteria for an effective test for Parkinson’s

No medical test is 100% accurate, although some come very close to this. With a test that measures Parkinson’s, it is likely that it will become more accurate as the condition advances and the changes caused by the progression of the condition become more pronounced. But when it comes to designing a test to improve diagnosis and measurement of the condition, there are a number of criteria that should be met:

  • Firstly, the test should detect Parkinson’s as early as possible with as few false negatives as possible— when a test says that someone does not have Parkinson’s when they actually do. In research papers this is called sensitivity. To have the greatest benefit, it is important that the test is sensitive to changes that happen early on in Parkinson’s as if it can only detect the condition after someone has already been diagnosed it will be less useful as a diagnostic test. However, such a test could still be useful to measure the progression of the condition.
  • Secondly, the test should give as few false positives as possible — when it says someone has Parkinson’s but they don’t. This is known as specificity. If a test is not specific enough it could lead to misdiagnosis of similar or related conditions as Parkinson’s.
  • Finally, the tests should be relatively simple and quick, carry few risks, and be as inexpensive as possible. After all, it may be possible to diagnose Parkinson’s from a brain biopsy but, when this would likely cause damage to the brain and comes at a high risk, such a test is not feasible. And the cheaper, quicker and simpler the test, the more likely it will be adopted.

Today, all over the globe there is an ongoing search for a test that matches the above descriptions. As a comparison, research suggests that clinical diagnosis of Parkinson’s as it currently stands in the absence of a definitive diagnostic test has a sensitivity of 88% and specificity of 68%.

Detecting molecular changes

Researchers are looking for subtle but measurable changes caused by the onset or progression of Parkinson’s that could help us detect and monitor Parkinson’s. They call these changes biomarkers and they are looking for them all over the body, in samples of tissues, blood and the fluid that surrounds our brain called the cerebral spinal fluid.

One of the candidates is the levels of alpha-synuclein, a protein known to be involved in Parkinson’s and thought to be responsible for the spread of the condition from cell to cell. You can read more about that here:

There have been a number of promising but inconclusive results looking at the levels of this protein in the cerebrospinal fluid, and some studies suggest there may be measurable differences between those with and without Parkinson’s that could be used as a diagnostic test when combined with other biomarkers particularly as the technology being used to detect different types of this protein improves. But to get a sample of cerebrospinal fluid, a lumbar puncture is required, which isn’t exactly a simple test. So is there another way to detect this protein?

Researchers have looked for differences in alpha-synuclein in the blood and in tissue biopsies, including from the skin and gut, with varying levels of success. In one study from Harvard University, researchers found a significantly greater amount of alpha-synuclein protein present in skin samples from those with Parkinson’s than control participants. Impressively the researchers suggest that the test was sufficient to serve as a diagnostic biomarker with >90% sensitivity and specificity.

When it comes to using alpha synuclein to detect Parkinson’s, more work in larger cohorts is still needed to demonstrate that this protein could accurately distinguish between those with and without Parkinson’s.

Researchers are also looking at the levels of other blood components, from antibodies to specific blood proteins and inflammatory markers. While there are far too many ongoing studies to list, some highlights include:

  • a study from 2017 suggesting that the levels of a protein involved in inflammation, called TNF, in the blood serum, when used along side alpha-synuclein levels in the cerebrospinal fluid, could detect Parkinson’s with a minimum of 82% sensitivity and 83% specificity.
  • research that made the headlines this year highlighting that the levels of caffeine and its byproducts in the blood could be used as a diagnostic test. Statistical analysis of the technique suggested an accuracy of 98%.
  • back in 2015, a study found that autoantibodies in blood samples could differentiate between people with and without Parkinson’s with a 90% accuracy, and between people with early and moderate Parkinson’s with an accuracy of 97.5%.

Over the past decade there have been plenty of encouraging results in the search for molecular biomarkers of Parkinson’s, but much of this research has been done in small scale studies and requires validation by other researchers in a greater number of samples. Fortunately efforts to accelerate the search for a biomarker of Parkinson’s are underway in the form of programmes such as the NINDS Parkinson’s Disease Biomarker Program, which has over 12,000 biosamples as part of this unique resource that supports new and existing research into biomarker discovery.

And it’s not just inside our bodies that chemical changes may be present, some of the latest research suggests that Parkinson’s could be detected by measuring protein levels in a sample of tears, or testing the chemicals in our breath. These changes, once too subtle to detect are now coming to light with the use of ultra sensitive detection techniques, and even super sniffing dogs.

Beyond molecular biomarkers

Not all changes in the body that are related to human conditions can be detected with a molecular test. In the hunt for a biomarker for Parkinson’s, researchers are also looking into subtle differences in the way the eye moves or in a person’s ability to draw a spiral, and are using the latest brain scanning equipment to produce detailed images of the structure of parts of the brain affected by the condition.

Research suggests such brain scanning techniques may be able to differentiate between those with and without Parkinson’s with a high degree of sensitivity and specificity. While there have been some difficulties replicating results studies have suggested measuring certain aspects of the brain using an MRI scan could differentiate between Parkinson’s and other conditions that have similar symptoms with an accuracy of 97%.

Over the last decade there has been significant advances in brain scanning techniques and machinery. These advances give hope that future brain scans could lead to an earlier diagnosis of Parkinson’s and possibly even detect the changes in the brain before symptoms of the condition become apparent.

How you can help researchers develop a test for Parkinson’s

We can only continue to make progress towards tests that can diagnose and monitor Parkinson’s with your help. There are a number of research studies that are currently looking for participants, both with and without Parkinson’s. For instance, in Manchester researchers need people to take part in research to find out if it is possible to accurately monitor Parkinson’s using a simple photograph of the eyes.

If taking part in research is something you would be interested in, you can find local opportunities using our take part postcode search.