Alzheimer’s Biomarker in the eye

Promising Alzheimer’s Biomarker Detected In the Human Eye

By | September 29th, 2020

A protein detected in the eye appears to be an important Alzheimer's biomarker that can help warn people years or decades early about the presence of the disease.

Increasingly, scientists have looked to the eye for clues to Alzheimer’s. Past studies have taken all angles, from identifying links between beta-amyloid clumps in the brain and yellow spots caused by deposits of fat and calcium underneath the retina’s top layer, to cognitive decline as signaled by small changes in ocular blood vessels, to the thickness and health of the retina in indicating Alzheimer’s onset. Retinal scans are being pursued as one of the fastest, least invasive and most affordable future ways to screen for the disease. Now, researchers have pinpointed a new diagnostic beacon: a well-known Alzheimer’s biomarker — also an indicator of other neurodegenerative diseases — is detectable in fluid within the eye.

The biomarker is called neurofilament light chain (NfL) — a protein resulting from brain damage that has been detected in cerebrospinal fluid and blood — which researchers are exploring as an indicator of neurodegeneration. A new study out of a lab at Boston Medical Center has found NfL in ocular fluid known as vitreous humor.

“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,”  first author Manju Subramanian, an ophthalmologic surgeon at Boston Medical Center, said in a news release.

“As an extension of the brain, the eye can provide important insight about what’s happening pathologically in the brain,” he added. Alzheimer’s disease affects one in 10 people over the age of 65 in the United States, but testing for a definitive diagnosis is difficult. As of now, no test can give a definitive Alzheimer’s diagnosis. Currently brain scans, which can be costly for patients and which require access to facilities with sophisticated equipment, are used to supplement findings of memory tests or other symptoms of memory loss. But it is often the case with neurodegenerative diseases that once symptoms appear, the disease is already progressing.

“The earlier we can diagnose and treat these diseases, the better off our patients will be,” Subramanian said.

While NfL is not yet used as a diagnostic tool in clinical settings, increasingly, research suggests it can be detected in blood and cerebrospinal fluid years or decades, before clinical symptoms of neurodegenerative diseases appear.

In the study, published in Alzheimer’s Research & Therapy, researchers set out to determine whether NfL was present in the eye and whether ocular NfL levels aligned with other known Alzheimer’s biomarkers, such as accumulations of beta-amyloid or tau proteins in the brain, by testing fluid samples were collected during routine eye surgery from 77 subjects, 63% male, at an average age of 56 years old.

Researchers detected the presence of NfL in the vitreous humor of all 77 participants, and found that higher levels of NfL were associated with higher levels beta-amyloid and tau. With further research, the team hopes to establish the detection of NfL as an early indicator of Alzheimer’s signature brain proteins, leaving more time for preventive or mitigative treatment.

“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,” Subramanian said.

He hopes the research will help to lay the foundation for future studies to investigate the potential of this biomarker to accelerate the diagnosis of Alzheimer’s, Parkinson’s and other neurodegenerative diseases.

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