Alzheimer's biomarkers can be found in eye fluid

The neurobiological hallmarks of Alzheimer’s disease are amyloid plaques and neurofibrillary tangles, both of which are specific neurological changes that occur in the brain at a microscopic level. This is why a diagnosis of Alzheimer’s disease can be so difficult in a living person: We can’t look at the brain under a microscope to check for plaques and tangles, which would be the only way to diagnose Alzheimer’s definitively. Currently, this can only occur by autopsy.

Recent imaging advances allow us to see the plaque buildup (amyloid) or tangles (tau) by way of an amyloid PET scan or tau PET scan, respectively. Amyloid PET scans are FDA-approved, but rarely ordered because insurance does not yet cover the procedure. Tau PET scans are used in research but have not yet been FDA-approved. Both procedures are costly and involve the injection of an isotope—a dye that binds to the amyloid or tau protein and lights up when the patient is in the scanner.

We can also measure for byproducts of plaques and tangles by looking in cerebrospinal fluid, the fluid that circulates in the brain and spinal cord. Insertion of a needle into the spinal cord allows for the withdrawal of fluid that can then be assayed, much like blood, for measures of specific components.

In unaffected individuals, amyloid levels in cerebrospinal fluid are high—an indication that amyloid is being cleared from the brain as it should be—and tau levels are low. For people with Alzheimer’s disease, the opposite is true: There are low levels of amyloid in cerebrospinal fluid and high levels of tau. Specific cutoff points for amounts of amyloid and tau to aid in diagnosis have not been fully standardized yet.

The quest for easily obtainable biological markers of Alzheimer’s disease is ongoing and far-reaching. Numerous groups are studying possibilities for blood markers. Genetic testing is also on the rise, but inconclusive because most forms of Alzheimer’s disease cannot be predicted by genes alone.

A group of researchers at Boston Medical Center recently reported that eye fluid may contain biological markers of Alzheimer’s disease. The researchers utilized eye fluid samples that would otherwise have been discarded from 80 patients who underwent eye surgery. They found that levels of amyloid and tau in eye fluid correlated with performance on a cognitive test: lower levels of these proteins correlated with lower cognitive test scores.

Correlation does not prove causation, so much more research needs to be done. In fact, there have been other groups who have advocated and studied the potential use of retinal examination for the presence of amyloid plaques. The premise is that the retina is an extension of the brain. Amyloid plaques in the brain have been correlated with amyloid plaque in the retina.

Experimental eye drops that stain for amyloid may be used with a medical device to detect the presence of amyloid plaque in the retina, which then may correlate with amyloid plaque in the brain. Such studies have also received media attention. And, another recently published study explores the relationship between dental gum plaque and brain plaque.

While none of these techniques is currently available for clinical use, as none have met the FDA criteria for approval, they are all a testament to the need for efficient, accessible diagnostic tools for Alzheimer’s disease. Time is brain and early diagnosis is critical to finding a cure. And, you never know, the answer could be more than what meets the eye.

For more information about Alzheimer’s disease diagnosis and access to potential treatments, please contact The CRCNJ at 973-850-4622.