Two clinical trials that use eye screening to detect early build up of amyloid in the brain were reviewed at the 2014 Alzheimer’s International Conference. Like the smell tests that were also reviewed at the AAIC, these eye screening tests are designed to identify people who are asymptomatic, but who are at high risk for developing Alzheimer’s.

Curry as a Staining Agent

One research group used curcumin, one of the ingredients in curry powder, to stain the retina to highlight a build up of amyloid.  CSIRO, the Australian national science agency, working with American researchers, selected the retina because it is part of the central nervous system. As described by the researchers, it is “a piece of the brain outside of the brain”. As it turns out, curcumin binds to amyloid, staining the deposits a bright yellow that is picked up by the researchers’ specially designed camera. The subjects also underwent a PET scan, which confirmed that the retina scan was a very accurate substitute for a PET scan in confirming the presence and amount of amyloid deposits.

The retina scanning trial is not finished. There are 200 people involved in the retina study. So far, the trial has finished scans of 40 of these subjects.  The results are impressive: The retina scans have accurately identified 100% of the subjects who have been diagnosed with Alzheimer’s, and ruled out Alzheimer’s in 80% of the subjects who did not have the disease.

Using the Lens as an Eye to the Brain

The other research trial has developed a screening protocol using the eye lense. It has just finished its Phase 2 testing. Conducted by a for profit company, Cognoptix, it uses an ointment and a laser scanner to measure the amount of amyloid in the lens of the eye.  The Phase 2 test used 40 subjects and identified those with Alzheimer’s with 85% accuracy. Cognoptix is starting its Phase 3 clinical trial, and hopes to have the test available for the public by 2016.

Implications of these Screening Tests

Both these trials are searching for a less expensive, less invasive, and more accurate screening tool to identify people who are asymptomatic for cognitive impairment, but who have high levels of amyloid in their brains. It is too soon to know if one of the eye tests or smell tests will become sufficiently refined to eliminate the need for any other screening. It is possible that physicians may use a panel of non-invasive tests to develop a clearer view of brain health.

Not only do these tests promise a cheaper and less invasive way of identifying those with high amyloid levels, they have other benefits:

• The tests do not use radioactive agents, so physicians can repeat them at intervals of 2 to 3 months. PET scans can be administered only once in a year.

• As new therapies are developed, frequent testing can track and quickly determine whether or not a therapy is effective.

• The retinal scan, and possibly the lens scan, show much more detail about the amyloid build up. These scans, especially when presented as a continuum, may lead to a better understanding of how amyloid builds, and what role it plays in the development of Alzheimer’s Disease.

Cautionary Notes

The eye screens both use the presence of amyloid as a proxy for nascent Alzheimer’s disease. However, the existence of amyloid plaques in the brain does not mean the person will develop Alzheimer’s Disease. As many as 30% of those with amyloid (also referred to a Abeta) never develop Alzheimer’s. Thus, these tests cannot be more accurate than the proxy they are designed to find.

Both trials are incomplete and have used small numbers of subjects. They will need to replicate their early results with larger groups before they are ready for use.

The main purpose of these screening tests, if ultimately proved to be accurate, will be to identify those who are at high risk for the disease. It will make the clinical trials of drugs targeting at risk populations more meaningful, and hopefully accelerate the discovery of effective therapies.