Lipofuscin In the Retina Marks Neurodegeneration.

In Brain Disorders, Brain Science, Dementia by Brainy Days Ahead

Research by scientists at the Gladstone Institutes and the University of California, San Francisco (UCSF), shows that lipofuscin in the retina and in blood cells could serve as an early marker of neurodegenerative disease. The two forms of neurodegeneration are frontotemporal dementia (FTD) and neuronal ceroid lipofuscinosis (NCL). FTD is one of the most common forms of dementia in adults under 65 years. NCL is the most common neurodegenerative disease in children and young adults. NCL is associated with a process named lipofuscin, which results in the excessive accumulation of fats and proteins called lipopigments in vulnerable cells and tissues of the body. The common factor in these diseases is the protein progranulin. Changes in progranulin expression affect the brain. When progranulin levels are low, brain cells die more readily when exposed to toxins. Mutations that lower progranulin levels cause FTD, whereas complete loss of progranulin leads to NCL. The research team took a close look at lipofuscin in humans who carry mutations in the progranulin gene. Because vision loss is one of the first symptoms of NCL, and it is accompanied by lipofuscin accumulation in the retina, the researchers first evaluated lipofuscin in the retina. They found that people who carry progranulin mutations were nearly twice as likely to have retinal lipofuscin deposits than healthy people. Following this initial discovery, the researchers evaluated the frontal cortex, the region of the brain most affected in FTD. Using postmortem tissues, the research team found that lipofuscin deposits also accumulated in neurons from the frontal cortex of people carrying progranulin mutations. This result suggests that restoring the levels of progranulin to normal may prevent or help treat multiple neurodegenerative disorders.