Measuring proteins in tears may help in diagnosing ALS, per study

It may be possible to diagnose amyotrophic lateral sclerosis (ALS) in part by measuring the amounts of proteins in the tears of a person thought to have the progressive neurological disease.

That’s according to a new study from Germany that found that quantifying levels of chitinases, a family of proteins linked to neuroinflammation, in tear samples may help in diagnosing ALS. The researchers found that tear levels of chitinase-3-like protein 1 (CHI3L1) showed a modest ability to differentiate people with ALS from those without.

Further, combining tear levels of the chitinases CHI3L1 and chitotriosidase (CHIT1) with blood levels of neurofilament light chain, or NfL — a commonly used marker of nerve cell damage — slightly improved the measure’s diagnostic performance, the team noted.

“These results suggest TF [tear fluid] chitinases and [blood] NfL could complementarily contribute to the diagnosis and monitoring of the disease, and call for further evaluation of TF as a biomarker source in ALS,” the researchers wrote.

Noting that tear fluid “can be collected non-invasively,” the scientists suggested that it “may represent a promising alternative” for studying chitinases.

Titled “Chitinases in Tear Fluid of Patients With Amyotrophic Lateral Sclerosis,” their study was published in the European Journal of Neurology.

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ALS is caused by the progressive loss of motor neurons, the nerve cells that control movement, which leads to muscle weakness. Neuroinflammation, or inflammation in the nervous system, is thought to play a role in ALS and has been associated with disease progression.

That process involves the activation of immune cells in the brain and spinal cord, together comprising the central nervous system. Researchers have long sought easy-to-access biomarkers to track these inflammatory changes over the course of the disease.

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CHIT1 and CHI3L, two chitinase proteins known to be involved in neuroinflammation, have been found at higher levels in the cerebrospinal fluid (CSF) — the liquid surrounding the brain and spinal cord — of people with ALS.

Now, researchers at the Technical University of Munich assessed whether levels of these two proteins in tears could serve as potential biomarkers for ALS. The team noted that tear fluid can be collected noninvasively, unlike CSF.

Their study involved 50 people with ALS and an equal number of individuals without evidence of neurodegenerative conditions. All were recruited between 2019 and 2025 at a university hospital in Germany. The ALS patients had an average age of 66, and 60% were men. The researchers noted that “both groups were well matched with regard to age, sex, [eye] disease, and medication.”

The team first analyzed the proportion of participants in both groups who carried a genetic variant known to reduce production of CHIT1. There seemed to be a “tendency [toward] a higher occurrence of the mutation in the ALS group,” the scientists noted. Specifically, the genetic variant was found in 34% of ALS patients and 28% of controls.

The four ALS patients who carried two copies of the mutation had undetectable CHIT1 in tear fluid and significantly lower levels of the protein in blood relative to those with only one mutated copy or no mutated copies, the data showed.

Participants in both the ALS and control groups carrying one copy of the variant also had significantly lower blood levels of CHIT1 compared with those without mutated copies, the researchers found. Tear CHIT1 levels were significantly higher in men than in women, both overall and among those with ALS.

Importantly, according to the team,, tear CHIT1 levels did not differ between people with ALS and controls, although the protein was found at significantly higher levels in the CSF of the participants with ALS (15.5 vs. 6.47 nanograms/mL).

In contrast, tear levels of CHI3L1 were significantly higher in people with ALS than in controls (8.22 vs. 5.96 nanograms/mL), but not in the CSF. Blood levels of neither protein differed significantly between the groups, per the team.

Statistical analyses adjusted for sex showed that tear CHI3L1 levels could distinguish people with ALS from controls with modest accuracy, of 66.8%, while tear CHIT1 levels showed a discriminative accuracy of 59.2%. Combining tear levels of both proteins was not superior to tear CHI3L1 levels alone at differentiating ALS patients from controls, the researchers found.

Tear CHI3L1 levels showed better diagnostic performance than CSF CHI3L1 levels, while CSF levels of CHIT1 and of both chitinases performed better than their measurements in tears or blood.

The researchers found no significant relationship between tear chitinase levels and measures of disease severity, duration, breathing capacity, or rate of ALS progression.

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Blood levels of NfL, an established marker of nerve fiber damage, showed better ability to distinguish people with ALS from controls, with an accuracy of 72.1%, the researchers noted.

Combining blood NfL with tear CHIT1 and CHI3L1 levels slightly improved this performance (74.1% accuracy), suggesting that the markers may provide complementary information about different aspects of ALS.

The researchers noted that, despite the differences observed between the groups, there was considerable overlap in chitinase levels between individual participants. This means the proteins are not currently suitable as standalone diagnostic biomarkers, but they may be useful for studying disease-related processes, per the team.

“These findings support the potential of combining [blood] NfL with TF chitinases as a minimally invasive approach that warrants further evaluation in larger [studies] for longitudinal monitoring and disease stratification,” the researchers wrote.

Overall, this work “supports the potential of [tear fluid] as a non-invasively collectable biofluid,” the team concluded, adding that “further studies using more sensitive analytical techniques and larger, independent cohorts are needed to expand on these findings.”