Can Tears Serve as a Biomarker for Alzheimer's Disease?

If you ask most people what separates humans from other animals, you’ll likely get at least one person who says it is language use. Yet there is another distinction that can be made, one that gets less attention, certainly. It is that only humans cry emotional tears as adults.

Humans and animals use a distress call to signal the need for help when they’re very young, but in humans, that distress call, and the visual signal of shedding tears, continue into adulthood, well past the point of language acquisition. The question of why we cry tears when we have a much more efficient and specific means of communicating through language is one that researchers are still investigating.

Why do we cry?

One old idea was that tears contain toxins that have built up inside us. Crying was thought to release this toxin and prevent the breakdown of the immune system that allowing the toxin to build up could have caused. Crying tears restores the balance of homeostasis in the body and allows our immune system to function as it should.

This idea was a compelling explanation for the persistence of crying into adulthood, but unfortunately, not one that is supported by the research. Chemical analysis of tears has shown that there is nothing toxic in the chemical makeup of the tears (Gross, Fredrickson, and Levenson, 1994) and a review of the literature found no consistent evidence that crying was beneficial to one’s health (Rottenberg, Bylsma and Vingerhoiets, 2008).

The link between tears and immune system function may still be worth studying, according to a 2016 study by Kalló, Emri, Varga, Ujhelyi, Tözser, Csutak, and Csösz. These researchers were investigating the possibility that tears may contain a biomarker for Alzheimer’s Disease (AD).

AD is the most common form of dementia, characterized by the accumulation of amyloid plaques, and tau tangles in the brain. Behaviorally, AD is characterized by progressive cognitive decline. At present, confirmation of a diagnosis of AD has to wait for an autopsy. A biomarker that could reliably indicate a diagnosis of AD early in the disease would be tremendously beneficial in helping the patient and caretakers improve their quality of life.

Pet scan of normal and AD brain

Source: Health and Human Services Department, National Institutes of Health, National Institute on Aging : p.24[1], Public domain, via Wikimedia Commons

Using tears as a biomarker

The tears that these researchers were interested in were not the ones that we shed when we’re very emotional, happy, or sad. There are several different kinds of tears, not all of which are evoked by our emotional state. All three types, basal, reflex, and emotional, are produced by the lacrimal system surrounding the eye.

Emotional tears are triggered by our emotional state, while reflex tears are elicited by an irritation of the eye—for example, when we’re slicing onions or when dust flies into our eye on a windy day. The purpose of reflex tears is to get rid of the irritation. Basal tears are shed constantly, coating the eye with each blink, preventing the eye from drying out and coating the cornea with protective lubrication.

It was these basal tears that Kallo, et al., were interested in because these tears create a chemical barrier on the surface of the eye, acting as part of the immune system. All three kinds of tears contain enzymes, lipids, metabolites, electrolytes, and proteins in varying amounts; the chemicals in basal tears are antibacterial and immunomodulatory, helping to protect us against disease. Their hypothesis was that since basal tears reflect the working of the immune system, and because inflammation is one proposed causal agent in developing AD, basal tears might function as an early warning system marker for AD.

Basal tears were collected from 14 patients who had been diagnosed with AD and 9 age-matched controls without the AD diagnosis. Tears were collected using capillary tubes (a standard, non-invasive collection technique that could easily be done at a patient’s bedside), and protein concentrations in the tear samples were measured using a variety of techniques. In addition, tear flow rate was assessed.

Chemistry of tears

Proteins and their biological processes identified in the tear fluid.

Source: Gustavo A de Souza, Lyris MF de Godoy and Matthias Mann, CC BY 2.0 via Wikimedia Commons

The results showed that the chemical composition of the basal tears secreted by AD patients differed significantly from that obtained from the control participants. Levels of several proteins known to protect the body against potentially harmful lipids, bacteria, and viruses and to have antibacterial, antimicrobial, and immunological effects (proteins like lipocalin-1, lactotransferrin, and licritin) were significantly lower in AD patients compared to controls. They also found that AD patients had a higher tear flow rate than did controls. These results suggest that tear chemistry might be an easily obtained potential biomarker for AD.