A new study shows that the eyes are telltale signs for understanding diseases of the brain. Scientists at the UCSF Weill Institute for Neurosciences found that retinal scans can distinguish vital changes in blood vessels that might provide an early sign of Alzheimer’s disease. These scans provide insight into how one of the most common Alzheimer’s risk genes (APOE4) gives way to the disease.
Fanny Elahi, MD, Ph.D., assistant professor of neurology, member of the UCSF Memory and Aging Center (MAC) and lead author of the study, said, “The most prevalent genetic risk for Alzheimer’s disease is a variant of the APOE gene, known as APOE4. We still don’t fully understand how this variant increases risk of brain degeneration, we just know that it does, and that this risk is modified by sex, race, and lifestyle. Our research provides new insights into how APOE4 impacts blood vessels and may provide a path forward for early detection of neurodegenerative disease.”
The effects of APOE4 capillaries in the brain have been studied in mice. Elahi has long suspected these tiny blood vessels might play a crucial role in Alzheimer’s disease due to their important functions through the blood-brain barrier, such as delivering nutrients and oxygen, ridding the body of waste, and monitoring immune system responses. Elahi says damage to these blood vessels could lead to multiple issues, including the protein buildup and cognitive decline seen in Alzheimer’s patients. Since we cannot visualize individual capillaries in living peoples’ brains, Elahi focused on the eyes instead.
Through a non-invasive eye scan, APOE4-associated capillary changes were detected in humans. Light-penetrating tissue shares biology with the brain, so researchers believe the retina might help establish APOE4 variants and how similar capillaries inside the brain are affected.
After analyzing the retinal scans, a reduced capillary density in APOE4 carriers was found, signifying an effect that increased with age. The team also compared the abnormalities found in the retinal scans to brain perfusion and found that people with higher density retinal capillary density also had greater brain blood flow.
Elahi said, “This is the first time that we have demonstrated in living, asymptomatic humans that the smallest blood vessels are affected in APOE4 gene carriers. That’s important because it suggests that the increased risk of brain degeneration and Alzheimer’s disease in APOE4 carriers might be through its effect on blood vessels. This is just the beginning. But the implications for early detection and possible intervention can be significant in combatting Alzheimer’s disease and other neurodegenerative disorders. It’s much harder to regenerate neurons than to stop their degeneration from happening in the first place. Similar to cancer, early detection can save lives.”
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