By analyzing the thickness of the retina, it would be possible to detect a familial form of frontotemporal dementia. The team also deciphered the mechanism behind the disease.
The retina, a “window to the brain. A recent study, published in the Journal of Experimental Medicine this August 25, opens new possibilities in the screening of the familial form of frontotemporal dementia. This neurodegenerative disease, which is characterized by behavioral and language disorders, could be detected earlier by analyzing the thickness of the retina.
Early thinning
Although located in the eye, the retina is made up of neurons directly connected to the brain. The study of this wall potentially represents a simple and accessible way to examine changes in neurons. As part of this study, the Gladstone institutes and the University of California at San Francisco (United States) followed patients carrying a genetic mutation responsible for frontotemporal dementia, which affects around 5,000 French people. Specifically, these people carry a gene that reduces the expression of progranulin, a key protein in the brain.
By observing the thickness of the retina, the researchers were able to spot the onset of frontotemporal dementia even before the usual symptoms appeared. Indeed, the patients carrying the genetic mutation had a thinner retina than the others. “These results suggest that the retina is a kind of ‘window to the brain’,” said Dr. Li Gan, who conducted the study. For him, these discoveries make retinal thinning “one of the earliest observable signs in familial frontotemporal dementia.” “
Avoid the death of neurons
If the retina is thinning, it is because the neurons that make it up are gradually dying. This mechanism is precisely at the origin of dementia: neurons in the frontal and temporal areas of the brain lose their function and die, resulting in cognitive symptoms. But until now, researchers have not known how this is possible.
Thanks to this study, the underlying mechanisms of the disease are more clear. The studied form of the disease is explained by a genetic mutation which underexpresses the protein progranulin. However, it is responsible for the correct localization of another protein, TDP-43. As this is no longer located outside the neurons, but in their heart, they lose their normal functioning and end up destroying themselves.
But by seeking how to counter this mechanism, the researchers highlighted a possible therapeutic avenue. A third protein, Ran, regulates the level of TDP-43. By increasing the expression of the first, it is possible to raise the levels of the second, despite the genetic mutation. This helps prevent neuron death.
“From these results, we know that retinal thinning may represent a pre-symptomatic marker of dementia, but we have also made progress in understanding the underlying mechanisms of frontotemporal dementia, and they could lead to the definition of new therapeutic targets ”, summarizes Dr Gan.
.
