Vitreous Biomarkers May Flag Early Alzheimer Disease

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Eye fluids may one day help diagnose some brain diseases earlier, according to researchers at Boston University Medical Center and colleagues who report a correlation between certain vitreous biomarkers and neurodegenerative changes in postmortem brain tissue. The findings, they report, may one day help diagnose conditions like Alzheimer disease in the early stages.¹

“While prior reports have shown that loss in the ganglion cell layer of the retina reflect dementia both pathologically and by imaging with OCT, this is the first study showing that biomarkers in eye fluid, specifically the vitreous, reflect brain pathology,” said study author Manju L. Subramanian, MD.

“Our findings provide further evidence to support the potential role of vitreous biomarkers in early diagnosis and prognostication of diseases like Alzheimer disease and chronic traumatic encephalopathy [CTE],” she said.

Finding a correlation. The researchers examined the postmortem brains and vitreous of 41 people who had Alzheimer disease (n=7), CTE (n=15), both Alzheimer disease and CTE (n=10), and no indication of neurodegenerative disease (n=9). Participants in the latter group, like all participants, had survived repetitive head injury (due to sports, military service, and physical violence, among other factors) but showed no signs of neurodegenerative disease, and served as the control.

The researchers measured levels of amyloid-β, eotaxin-1, neurofilament light chain, phosphorylated tau, and total tau proteins—vitreous humor biomarkers previously correlated with impaired cognitive function.^1,2,3 The vitreous total tau was significantly higher in the only-Alzheimer group (p=0.08) and the only-CTE group (p=0.08) compared with the Alzheimer disease-CTE combined group and the control group.

Surprise finding. Vitreous neurofilament light chain was not associated with confirmed neuropathological diagnosis, but it was associated with CTE. Specifically, it was linked with low stage CTE versus no CTE, as well as low stage CTE versus high stage CTE.

“While we hypothesized that proteins in the vitreous would be significantly altered in those with Alzheimer disease, we were surprised to find that neurofilament light chain is significantly associated with CTE, a neurological disorder seen in some professional athletes, military personnel, or anyone with a history of traumatic brain injury,” Dr. Subramanian said.

Up next. The researchers plan to investigate the aqueous as a potential reservoir for protein markers for Alzheimer disease. They also want to validate these biomarkers using more traditional Alzheimer disease diagnostic modes, such as MRI, PET scan, and cerebrospinal fluid in living patients.

Working toward earlier diagnosis. “Alzheimer disease pathological changes occur in the brain 10-20 years prior to the onset of symptoms, at which point it’s often too late for therapeutic drugs to have any meaningful effect. This is why finding a screening test for Alzheimer disease in the pre-symptom phase is so important,” Dr. Subramanian said.

Currently, Alzheimer disease and CTE can be confirmed only after a patient dies and an autopsy of the brain is performed, so the study findings could potentially shift diagnosis from postmortem analyses to using noninvasive diagnostic criteria revealed in certain biomarkers. “If eye biomarkers become the method of Alzheimer disease screening, then one may consider screening during a yearly eye exam or cataract surgery,” Dr. Subramanian said.

“The eye is certainly a window to our brain,” she added. “Our findings confirm this connection through the eye’s reflection of pathological changes in the brain for both Alzheimer disease and CTE.”

—Miriam Karmel

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1 Vig V et al. J Alzheimers Dis. 2023;93(3):1181-1193.

2 Wright LM et al. J Alzheimers Dis. 2019;68(4):1429-1438.

3 Subramanian ML et al. Alzheimers Res Ther. 2020;12(1):111.

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Relevant financial disclosures: Dr. Subramanian—None.

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