Early signs of Alzheimer's are in the eye
A simple eye test could soon help diagnose Alzheimer's, Parkinson's and Huntington's (Image: Bruce Ayres/Stone/G
Your eyes reveal a lot about you, and now that includes the health of your brain. A new way of counting dying eye cells could allow Alzheimer's disease to be diagnosed and treated in its early stages.
Many neurological diseases – including Alzheimer's, Parkinson's and Huntington's – involve the death of neurons in the brain, but these events are extremely hard to detect.
"It's difficult to diagnose these conditions before considerable damage has taken place, because the symptoms don't show up straight away," says Francesca Cordeiro at University College London.
However, this cell death also tends to extend to cells at the back of the eye, where it is much easier to detect abnormalities. So Cordeiro and her colleagues set about creating a way of detecting these eye neuron deaths.
Cell death can occur in one of two ways – a tidy "suicide" known as apoptosis, or a messy cell "explosion" called necrosis. In neurological disorders, most neurons die by apoptosis early in the disease, whilst necrosis happens later on.
In order to distinguish between these two types, the researchers used a green dye that binds to a protein expressed by cells undergoing apoptosis, and a red one that binds to the insides of exploded cells.
The team injected the dyes into the eyes of healthy mice and mice with a form of Alzheimer's disease and waited until any unbound dye was washed away. Then the researchers peered into the back of the mice's eyes using an ophthalmoscope – the microscope that optometrists use to look at human eyes.
Adding filters to the ophthalmoscope allowed the researchers to see the dyes fluorescing as differently coloured dots, each one announcing the death of a cell.
They found that there were many more dots of both colours in the mice with Alzheimer's than in healthy mice, an indication that more cells were dying in both ways in the eyes of these mice. Over time, they found that as Alzheimer's progressed, the number of green dots decreased and red dots increased.
The group hope that their technique could help doctors and opticians to diagnose Alzheimer's and other neurological diseases earlier than is currently possible.
It might also be possible to use the technique to work out how far a disease has progressed, allowing doctors to prescribe the therapy that is most appropriate to each patient.
"If most of the dying cells are undergoing apoptosis, the disease is likely to be in an early stage, and these cells could potentially be rescued," says Cordeiro.
In the mice, her team managed to reverse the process of apoptosis in eye cells that had started undergo it, by giving them the Alzheimer's drug memantine.
"If this method can be translated to humans, it would be a major advance in our research tools," says Helen Danesh-Meyer, professor of ophthalmology at the University of Auckland in New Zealand. "I would be very positive about using this new technique in my patients if it became readily available."
However, Denise Valenti, an optometrist at Harvard Vanguard Medical Associates, based in Braintree, Massachusetts, is not convinced about a clinical application.
"Techniques that involve tagging or injections can create issues of access as well as cost and safety," she says. But she says the research is "very relevant, especially for developing more effective animal studies of drugs".
Cordeiro says the group hopes to develop a safe marker that can be administered as eye drops and to test the imaging technique in people later this year.
Journal reference: Cell Death and Disease, DOI: 10.1038/cddis.2009.3