Keeping an eye on neurodegeneration

Potential biomarker for Alzheimer’s, Parkinson’s and other diseases can be found in the eye

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BOSTON—Boston Medical Center researchers have done a study indicating that a well-known biomarker serving as a means for earlier diagnosis of neurodegenerative diseases is now detectable in the eye.

Biomarkers—a major focus of neurodegenerative disease research in recent years—may help to detect the presence of a disease in earlier stages based on clues found in other parts of the body. Previous studies have shown that amyloid-β and tau proteins are biomarkers for Alzheimer’s disease, and they have been detected in cerebrospinal fluid, blood and in fluid around the eye.

The researchers identified neurofilament light chain, a protein previously detected in cerebrospinal fluid and blood that is being explored as a biomarker to detect neurodegeneration, in the vitreous humor (fluid within the eye). The results, which were published in Alzheimer’s Research & Therapy, may establish a foundation for future studies to investigate the potential of this biomarker to accelerate the diagnosis of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases.

In these diseases, nerve cells in the brain or peripheral nervous system lose function over time, eventually leading to cell death. Although there are treatments to address the physical and mental symptoms associated with these progressive diseases, there are no known cures, so early treatment is critical.

According to Dr. Manju Subramanian, an ophthalmologic surgeon at Boston Medical Center and the study’s first and corresponding author, “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.” He explained that neurodegenerative diseases are currently diagnosed based on clinical presentation and diagnostic testing. Once symptoms appear, it means that the disease is already progressing. As the number of people living longer has increased over the previous decades, the prevalence of neurodegenerative diseases has also increased. According to the National Institutes of Health, Alzheimer’s disease and Parkinson’s disease are the two most common neurodegenerative diseases.

In the study, the researchers collected eye fluid samples from 77 patients undergoing eye surgery at Boston Medical Center. Sixty-three percent of the subjects were male, and the average age was just over 56. All 77 patients had neurofilament light chain in their vitreous humor. Higher levels of this biomarker were associated with higher levels of other biomarkers known to be associated with Alzheimer’s disease, including amyloid-β and tau proteins.

Says Subramanian: “Our study is foundational because we established that neurofilament light chain (NfL) can be measured in eye fluid. We also found that its presence is not related to a patient’s local eye disease, suggesting that the measured levels may be due to something going on in the body or brain. But we have not yet provided evidence that its presence is linked to neurodegenerative disease in the body, so further studies are needed.

“When and if that is established, then we can consider measuring NfL in the eye as a potential diagnostic tool.”

He added that the best screening tool is one that is low-cost and relatively noninvasive with few side effects, such as a blood test. Current methods for the diagnosis of conditions such as Alzheimer’s disease include MRI scanning, PET scanning and lumbar puncture to test the cerebrospinal fluid; however, all of these methods are either too expensive or too invasive (or both) to be applied broadly.

“The vitreous humor sits in the back of the eye and currently requires a procedure (in the operating room) to remove from the eye, making it both invasive and expensive—similar to a lumbar puncture—so it would not be practical at this point to sample vitreous humor as a diagnostic test or screening tool,” he notes.

The research team is currently looking at fluid in front of the eye—the aqueous humor, which is slightly more accessible than the vitreous humor—to determine if it contains measurable biomarkers such as NfL.

The next step, according to Subramanian, is to definitively link NfL or other biomarker levels in the eye to diseases like Alzheimer’s and Parkinson’s diseases by correlating those levels to changes on MRI scans, PET scans or biomarkers within the cerebrospinal fluid.

“At this time, our data doesn’t support using eye fluid for testing. Once it does, a timeline can be formulated,” he says.

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