By Rich Haridy, September 21, 2020
A protein associated with neurodegeneration, previously detected in blood samples, has now been found in eye fluid
A protein, previously found to be an effective blood-based biomarker of neurodegenerative diseases such as Alzheimer’s, has for the first time been detected in the eye. The discovery lays the foundation for promising new diagnostic eye tests hoping to catch neurodegenerative diseases years before symptoms appear.
“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,” says Boston Medical Center’s Manju Subramanian, first author on the new study.
Neurofilament light chain (NfL) is a protein released as a result of brain cell damage. Although it is not yet used as a diagnostic tool in clinical settings, a growing body of research is finding it can be detected in blood and cerebrospinal fluid many years, or even decades, before clinical symptoms of neurodegenerative diseases appear.
In this new study, researchers set out to determine whether NfL can be detected in the eye, and whether these levels in the eye correlate with other biomarkers of Alzheimer’s disease progression. Eye fluid samples were collected during routine eye surgery from 77 subjects, at an average age of 56 years old.
NfL levels were successfully detected in all 77 subjects. Increased levels of NfL were effectively associated with higher levels of other biomarkers of Alzheimer’s such as amyloid and tau proteins. And perhaps most importantly, these eye-related NfL levels were not associated with any clinical eye diseases, or general systemic diseases, including diabetes. This particular finding adds weight to the hypothesis NfL levels are directly related to neurodegenerative disease.
A large body of recent study has been investigating ways non-invasive eye tests can be used to catch Alzheimer’s disease years before symptoms appear. The most successful tests leverage a technology called OCTA, or optical coherence tomography angiography.
Despite extraordinarily promising data linking OCTA measurements to the very earliest stages of Alzheimer’s neurodegeneration, there have been conflicting results. This suggests OCTA data can be confounded by co-existing eye disease.
The new study suggests finding a quantifiable protein-based biomarker, such as NfL, in eye fluid offers an additional, and potentially more specific, predictive marker for neurodegenerative disease. Of course, it is important to note this study is preliminary, and further validation studies will be required to examine NfL levels in eye fluid from patients at various stages of Alzheimer’s disease.
The study also notes the ocular fluid samples used in the research were obtained during eye surgery, and the researchers are realistic about the challenges they face in translating these findings into a practical clinical test.
The next step for the research will be to explore whether NfL levels can be detected in more accessible eye fluids, such as tear secretions. If a less invasive way of procuring ocular fluid can be effectively demonstrated then broad eye testing could be deployed as an early diagnostic for many neurodegenerative diseases.
“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,” says Subramanian. “The earlier we can diagnose and treat these diseases, the better off our patients will be.”
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