Testing Tears Could Aid Parkinson's Diagnosis

February 23, 2018

Testing an individual's tears for the presence of certain biomarkers could allow easier diagnosis of Parkinson's disease, a new study suggests.

"Assessing levels of certain proteins associated with Parkinson's disease — particularly α synuclein — in tears may be a reliable, inexpensive, and noninvasive test for the condition," lead author, Mark Lew, MD, Keck School of Medicine, University of Southern California, Los Angeles, told Medscape Medical News.  

The study will be presented at the American Academy of Neurology (AAN) 70th Annual Meeting in Los Angeles, April 21 to 27, 2018.

Lew explained that identifying an easy-to-measure biomarker for Parkinson's would be very helpful, especially if it could be detected early in the disease course.

"While we can diagnose Parkinson's quite effectively in patients with later disease after they have developed motor symptoms, earlier diagnosis is problematic," he said. "Patients may first experience other symptoms, including reduced sense of smell, sleep disturbances, depression, and constipation, alongside very few motor symptoms or even none at all. These other traits are very nonspecific and could be due to many different underlying conditions." 

A test that could identify Parkinson's disease in patients with very early symptoms might in the future make it possible to start disease-modifying treatments much earlier, which could slow the disease course, he added.

"While we don't really have such treatments at present, there are several promising therapies in trials and it is likely that there will be disease-slowing medications available down the line," he said. "There are also many conditions which resemble Parkinson's disease but are not actually Parkinson's disease, and it would be very useful to have a test that distinguished these different conditions."

Lew noted that he and his colleagues had done some preliminary studies with saliva but ran into difficulties with the assay because concentrations of the target proteins were very low.

"We had the opportunity to work with some ophthalmologists who have previously found potential biomarkers for some other disorders in tears, so we thought we would look for Parkinson's biomarkers in tears as well."

For the study, the researchers tested tears from patients with Parkinson's and age-matched controls for concentrations of several proteins associated with Parkinson's disease.

This was done by using the Schirmer test, in which wherein a small piece of paper placed on the eye absorbs moisture. A few drops of anesthetic drops are administered first.  

"It is a relatively noninvasive and simple process," Lew said.

The researchers analyzed the tear fluid collected for concentration of α synuclein, CC chemokine ligand 2 (CCL-2), and DJ-1 (Parkinson's disease protein 7).

Results are so far available for 55 patients with Parkinson's disease of varying severity and 27 age- and sex-matched controls. These show that levels of total α synuclein decreased significantly in patients with Parkinson's disease (423.12 pg/mg) compared with  healthy controls (703.61 pg/mg; P = .05) but that oligomeric α synuclein increased significantly in patients with Parkinson's (1.45 ng/mg) relative to controls (0.27 ng/mg; P = .0007).

While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson's and controls.

"We found lower levels of the monomeric form of α synuclein but a sixfold increase in levels of the oligomeric form in Parkinson's patients than in controls," Lew commented.

He explained that α synuclein is found in many parts of the body, and in Parkinson's disease it tends to clump together in the oligomeric form, which become the toxic Lewy bodies characteristic of the condition. 

"So our observation of lower levels of the monomeric form and higher levels of the oligomeric form seen in the tears of Parkinson's disease makes sense and is what we might expect."

The researchers conclude: "To our knowledge this is the first report of tear collection and protein analysis as a possible non-invasive, inexpensive and reliable biomarker for Parkinson's."  

"It appears from our results that the oligomeric form characteristic of Parkinson's occurs in fairly high concentrations in the tears and it is reasonably easy to measure," Lew added.

He also pointed out that tears are a suitable medium to use for a test because they are "cleaner" than some other fluids. For example, saliva has many issues of contamination as the mouth is full of bacteria and foods, whereas this is less of an issue for the eyes.

These are only preliminary results from the study in a limited number of individuals. Lew will present more data from larger numbers of participants at the AAN meeting, but he says he does not expect the results to change.

The researchers are planning to continue to expand the study to include more patients and controls to allow subgroup analysis.

"We would like to be able to drill down and look at particular groups. It would be interesting to see if the oligomeric α  synuclein is similarly increased in different types of patients — men and women, patients with earlier and later disease, et cetera," he said. 

The study was supported by the Michael J. Fox Foundation and the Plotkin Foundation.

American Academy of Neurology (AAN) 2018 Annual Meeting, April 21-27, 2018.

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