Biomarker for accurate and early diagnosis of Parkinson’s revealed

It is indisputable that the film “Back to the Future” is a classic of the 80s, whether for its dynamism, its great plot, its sequels or because it presented us with the idea of ​​being able to travel in time. Today Michael J. Fox, the actor who played the famous time traveler Marty McFly, suffers from Parkinson’s and was diagnosed in the 90s, when he was 29 years old. Because of this, the actor created a foundation that strongly supports The Parkinson’s Progression Markers Initiative (PPMI), which seeks to find new ways to diagnose this disease and provide timely treatments before the disease worsens.

Parkinson’s is a neurodegenerative disease in which neurons that release dopamine, which are responsible for controlling movements, are lost. This pathology affects the lives of 1.6% of the population over 65 years of age worldwide. The cause of Parkinson’s is currently unknown, however, great efforts have been made to find specific markers that give indications of the development of this disease when it is not yet established.

A specific marker is defined as a molecule that allows a precise diagnosis of a disease, with the lowest possible probability that the result indicates that the person is sick when in fact they are not. There are early symptoms that indicate that a person may have Parkinson’s. The most common are: tremors, loss of smell, sleep problems, difficulty walking, low voice and lack of facial expression, among others. However, these symptoms are not specific, which is why an accurate test is necessary.

A specific Parkinson’s marker that has been studied in recent years is alpha-synucleinwhich is a protein in neurons that works incorrectly in people with Parkinson’s. A protein works correctly when it has a defined shape, however, if there are errors in its shape it is said to be misfolded and this leads to malfunction.

When proteins are misfolded, they are more likely to stick together and form clumps. In people with Parkinson’s, the protein alpha synuclein folds incorrectly and forms clumps of damaged proteins, called Lewy bodiesThis misfolded protein can be studied thanks to a test that maintains the same principle as the PCR test used to diagnose COVID-19. The test is called alpha-synuclein seed amplification assay (from now on synuclein assay) and is capable of specifically searching for this Parkinson’s biomarker.

PPMIwhich as we mentioned in the introduction, is an initiative funded by the Michael J. Fox Foundation, recruits people with Parkinson’s from around the world and seeks to find biological markers of risk, onset and progression of Parkinson’s, in order to detect the disease before symptoms develop, and boy have they made progress!

Synuclein test

A 2023 study led by Professor Andrew Siderowf of the University of Pennsylvania published in The Lancet Neurology, analyzed 1,123 participants from PPMIseparating them according to sex, age, genetic characteristics and symptoms they presented.

All of these patients underwent a test to detect alpha-synuclein from cerebrospinal fluid (fluid that circulates through the spaces in the brain and spinal cord) to see with what specificity Parkinson’s could be diagnosed thanks to this test. Research has shown that the synuclein assay can detect with 87% accuracy whether a person has Parkinson’sWhat’s more, when people had a loss of smell and had not been diagnosed with Parkinson’s, the test was 97% accurate.

In addition to this, the synuclein test indicated that a group of patients had Parkinson’s before it could be detected by a CT scan, which is the most effective current method for detecting dopamine alterations in the brain and providing an early diagnosis of Parkinson’s.

In this way, the test could be highly effective in detecting the disease early, when brain images do not indicate any alteration. This is why the study is so important, showing that this biomarker could change the way Parkinson’s is diagnosed today.

Lewy bodies

Another important finding is that the marker was able to predict the presence of Lewy bodies in the brain. In order to accurately diagnose whether a person has these misfolded protein clusters, their brain must be examined after they have died, that is, post mortem. When they performed autopsies on the patients who tested positive for synuclein, they found that all of them had Lewy bodies in the brain. Therefore, this would indicate that it is an excellent marker in life of the existence of these conformations in the brain of people with Parkinson’s.

Despite the high specificity shown in the study carried out, The use of this marker still needs to be thoroughly analyzed before being used routinely, because researchers found that the test lost value in cases of patients who still had a sense of smell and also in cases of female patients.Therefore, it may be more appropriate to use this test as an adjunct to all the tests that a person with suspected Parkinson’s should undergo, rather than as the sole form of diagnosis.

So, What is the real value of studying this marker? As the researchers explain, the great advances found so far could change the way Parkinson’s is treated. They say that thanks to this marker, more specific therapies can be developed when patients test positive, since it will allow timely initiation of treatment when other tests have not shown any damage to the brain.

In conclusion, this is a great step towards an increasingly early diagnosis of Parkinson’s. This is the first large-scale study that allows us to know the specificity of the test that detects synuclein pathology, however, there is still a lack of studies that allow us to determine the prognostic potential of this test in order to use it as a routine examination in the diagnosis of Parkinson’s. There is still much to study, but with each investigation the PPMI is closer to achieving its goal and helping millions of people around the world.

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*This article arises from the agreement with the Interdisciplinary Center for Neuroscience of the University of Valparaíso.