Doctors in England have developed a simple eye test that might diagnose Alzheimer's, possibly enabling them to catch the disease early enough for more effective treatment.

In the study, published Thursday in the new online journal Cell Death & Disease, doctors injected mice afflicted with an Alzheimer's-like disease with two fluorescent dyes.

The dyes, markers for cell injury and death, lit up certain ailing nerve cells in the retina. The doctors, by using a widely available tool known as a confocal laser ophthalmoscope, could look into the eyes of the mice to see how sick the cells were, and thus how far the disease had progressed, long before the animal would show any "clinical" symptoms.

Although marking dying retinal nerve cells with dyes has long been done in "test tube" studies, this is the first time the results have been shown in a living animal.

"What we really think we're seeing are the early signs [of Alzheimer's]," says Francesca Cordeiro, M.D., Ph.D., lead author of the study, a professor of glaucoma and neurodegeneration studies at University College London, and an attending physician at the Western Eye Hospital in London. "These are the warning signs of the first processes of the disease that occur in the brain."

WINDOWS TO THE BRAIN

The technique works because eyes are the windows to, if not the soul, then at least the brain.

"The retina is a 'microscope dish' of cells that come from the brain," says Dr. Cordeiro.

Some cells in the retina, specifically the retinal ganglion cells, which pick up signals from light-sensing rods and cones, are actually neurons.

Since diseases like dementia devastate neurons, the doctors reasoned, they would also destroy the nerve cells in the retina. But there is one difference: unlike cells in the brain, encased in skin and a thick skull, cells in the eye live in a transparent medium, and thus, with the right instruments, are visible.

To do the study, the doctors used transgenic mice afflicted with a disease similar to Alzheimer's, exhibiting proteins, such as amyloid beta, also found in humans suffering from dementia.

Importantly, the two dyes the researchers injected into the mice, annexin V and propidium iodide (PI), detect two different stages of cell injury. Annexin tags cells undergoing early-stage apoptosis, or cellular suicide, which is thought to be reversible, and where treatments might be most effective.

"In the early stages of apoptosis, there are some molecules which move from the inside of the cell to the outside of the cell. The annexin just latches onto those," explains Dr. Cordeiro. "Anything that is positive for annexin is a cell that has these early molecules externalized...marking the cell as being sick."

By contrast, PI can only enter the cell when the cell wall has been damaged beyond repair, and is suffering late-stage apoptosis or is actually necrotic.

"In the case of the other dye, propidium iodide, it only enters cells where the membrane is no longer attached," says Dr. Cordeiro. "PI can then go into the cell, and it goes into the nucleus and marks the DNA."

CLINICAL TRIALS

With the success of this study, showing in principle the technique works in live animals, Dr. Cordeiro hopes to move forward to clinical trials. Recruitment has already begun, and she expects to begin trials likely in the second half of the year.

In these next studies, she'll be looking mainly for glaucoma, not Alzheimer's, as previous work suggests early nerve cell death in the eye might predict the disease nearly 10 years before it becomes visible to other clinical tests.

"Hopefully, if we get the funding, maybe even next year, once it's been shown that it works in patients [for glaucoma], we'll move on to different diseases," she says.

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