Eye Test for Alzheimer’s Diagnosis, Status Monitoring

A team of British, Italian, and American scientists has been looking into a technique that uses an ophthalmoscope and fluorescent markers to detect cell apoptosis in the retina. Because retinal apostosis is directly related to cell death within the brain, the technique should provide a diagnostic modality of gauging the status of Alzheimer’s and other neurological diseases.

In this study, we use spectrally distinct, well-recognised fluorescent cell death markers to enable the temporal resolution and quantification of the early and late phases of apoptosis and necrosis of single nerve cells in different disease models. The tracking of single-cell death profiles in the same living eye over hours, days, weeks and months is a significant advancement on currently available techniques. We identified a numerical preponderance of late-phase versus early-phase apoptotic cells in chronic models, reinforcing the commonalities between cellular mechanisms in different disease models. We showed that MK801 effectively inhibited both apoptosis and necrosis, but our findings support the use of our technique to investigate more specific anti-apoptotic and anti-necrotic strategies with well-defined targets, with potentially greater clinical application. The optical properties of the eye provide compelling opportunities for the quantitative monitoring of disease mechanisms and dynamics in experimental neurodegeneration.

The technique uses fluorescent markers that attach themselves to the relevant cells and indicate the stage of cell death. The retina is then observed using a customised laser ophthalmoscope. Until now, this kind of technique has only been used in cells in the lab, rather than in live animals. This research is therefore the first ever in vivo demonstration of retinal nerve cell death in Alzheimer’s Disease.
Professor Cordeiro, UCL Institute of Ophthalmology, said: “The death of nerve cells is the key event in all neurodegenerative disorders – but until now it has not been possible to study cell death in real time. This technique means we should be able to directly observe retinal nerve cell death in patients, which has a number of advantages in terms of effective diagnosis. This could be critically important since identification of the early stages could lead to successful reversal of the disease progression with treatment.

Image: Retinal images of a living 14-month Alzheimer Triple Transgenic mouse (a) compared to an aged control living mouse (b). Many more retinal nerve cells are in the early phase of apoptosis (green spots) in the Alzheimer mouse.
Press statement from University College London: How an eye test could aid Alzheimer’s detection…
Abstract in Cell Death and Disease: Imaging multiple phases of neurodegeneration: a novel approach to assessing cell death in vivo