A Neurodegenerative Disease Biomarker That Can Be Detected in the Eye

Neurofilament light chain is a well-described biomarker that is under extensive study in the early detection of neurodegenerative diseases. While the putative neurological biomarker is typically detected at elevated levels in the cerebrospinal fluid (CSF) and blood, researchers have now found that it can also be measured in the fluid within the eye, known as the vitreous humor.

Researchers at Boston Medical Center found that neurofilament light chain was detectable in the vitreous humor of the eye and was significantly associated with other markers of neurodegeneration, including amyloid beta and t-tau, as well as certain inflammatory and vascular proteins in the vitreous.

The research was published in the journal Alzheimer’s Research & Therapy. The researchers say that the results of the study help lay the foundation for future studies to explore the potential of this biomarker to accelerate the diagnosis of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and others.

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The neurofilament light chain protein has been shown to have promise as a predictive and prognostic biomarker in the early detection of various neurologic diseases in both adults and children, including genetic frontotemporal dementia and Alzheimer’s disease.

The presence of the neurofilament protein in the blood or CSF is reflective of neuronal axon damage in a wide range of neurodegenerative disorders.

In diseases like Alzheimer’s and Parkinson’s, axon damage in the brain or peripheral nervous system results in nerve cells losing their function, eventually leading to cell death. With no known cures and treatments that only help alleviate physical and mental symptoms associated with these neurodegenerative diseases, early diagnosis and early treatment interventions are key as they can help delay disease progression.

“One of the biggest priorities in Alzheimer’s disease research is to develop ways to diagnose the disease before the onset of symptoms, which would allow for early treatment that could help halt the progression of this fatal disease,” said the study’s first and corresponding author Manju Subramanian, MD in a news release from the Boston Medical Center. Subramanian is an ophthalmologic surgeon at the Boston center.

Neurodegenerative diseases are currently diagnosed based on clinical presentation and diagnostic testing – once symptoms appear, it means that the disease is already progressing.

The detection of neurodegenerative diseases at early stages is a subject of intense study, with neurodegenerative biomarkers being a significant area of focus in the field, given their potential for being able to detect disease early, preferably before symptoms present.

Alongside elevated amounts of amyloid beta and tau protein, increased levels of neurofilament light chain in both the CSF and blood have been shown to differentiate healthy individuals from those with Alzheimer’s disease with reliable accuracy.

The study researchers decided to look at neurofilament light chain levels in the eye given its intimate connection to the brain; they both also have a common embryological origin and vasculature. “As an extension of the brain, the eye can provide important insight about what’s happening pathologically in the brain,” added Subramanian, who is also an associate professor of ophthalmology at Boston University School of Medicine.

Moreover, epidemiological studies have shown that diseases of the eyes, such as cataracts, glaucoma, macular degeneration and diabetic retinopathy are associated with Alzheimer’s disease, suggesting that eye disease and Alzheimer’s could possibly share common risk factors and pathological molecular mechanisms. This provided a rationale for the researchers to investigate neurofilament light chain levels in the vitreous humor of the eye.

Paving the Way for Rapid and Early Diagnosis of Alzheimer’s

In the study, the researchers collected eye fluid samples from 77 patients who were undergoing previously scheduled eye surgery. The average age of the participants was slightly over 56 years old and 63 percent of them were male.

All 77 patients exhibited the presence of neurofilament light chain in their vitreous humor, with higher levels of the biomarker associated with high levels of the more established neurodegenerative markers, amyloid beta and tau proteins. Neurofilament light chain did not appear to be associated with the condition of the eye as levels of the protein were not significantly associated with any kind of eye disease.

“We hope that these results will add another way to use information about what’s happening in different parts of the body to detect the presence of disease before neurodegeneration takes hold, causing irreversible damage. The earlier we can diagnose and treat these diseases, the better off our patients will be,” said Subramanian.

Measuring levels of neurodegenerative disease biomarkers in the eye is potentially less invasive and easier than looking at levels in the blood or CSF. Since there are no curative treatments for neurological diseases like Alzheimer’s and Parkinson’s, early detection that is easy and rapid is key to the implementation of early interventions that can help slow disease progression.

With over 5.5 and one million Americans currently living with Alzheimer’s disease and Parkinson’s disease, respectively, they are the two most common neurodegenerative diseases in the country, according to the National Institutes of Health (NIH). And these figures are only expected to rise as the number of people living longer continues to increase.