Mitochondrial damage could explain why people suddenly develop Alzheimer’s disease, according to researchers from the Shibaura Institute of Technology. A process in the cell can increase oxidative damage, causing mitochondria to be altered and eventually lead to cell death.
The mitochondria produce energy for the cell and it needs the mitochondrial electron transport chain to do its job. But the problem is that using it produces reactive oxygen species (ROS) that attack tissue and cause oxidative damage. ROS damage can alter the mitochondria, forcing cells to die from a lack of energy to sustain themselves. Since the brain uses more oxygen than any other organ, it is at a higher risk for ROS damage.
Past research has found that ROS is a contributor to the spread of amyloid-beta plaques, a hallmark of Alzheimer’s disease. Another study found that oxidation levels were higher in older rats with insufficient vitamin E levels. The researchers studied these different links and predicted that since ROS damages the mitochondria and forces cells to die, then mitochondrial dysfunction could explain why people develop Alzheimer’s.
Using mouse models genetically altered to reflect an Alzheimer’s brain, the researchers tested the cognitive and motor abilities of mice 3, 6, and 20 months old. Compared to the control group of healthy, the mice with Alzheimer’s took longer to navigate and find their way out of a maze. In another test where they had to stay on a spinning rod to avoid falling, mice with an Alzheimer’s brain stayed on the rod for longer compared to control mice that quickly fell off. “The difference in fall time could be attributed to the weight difference between the two groups, as the control mice were heavier than the AD mice,” said Dr. Koji Fukui, study author of the paper in a statement. The findings suggest the mice with Alzheimer’s had cognitive problems but no issues with their motor abilities.
The mice brains were then examined and researchers collected tissue samples from several brain areas to measure signs of oxidation. They found high levels of the amyloid-beta plaque that increased with age. Further, one protein amyloid-beta1-42 was significantly higher in the hippocampus than other brain areas, suggesting increases in amyloid-beta1-42 were responsible for cognitive impairments in the mice.
They next looked for evidence of ROS-induced mitochondrial damage by measuring the levels of mitochondrial oxidative enzymes, including nicotinamide-nucleotide adenylytransferase (NMNAT)-3 which has anti-aging effects. In the Alzheimer’s brain, researchers found a decrease in NMNAT-3 and an increase in 3-nitrotyrosine (3-NT), a sign of high oxidation.“With reduced levels of NMNAT-3 and higher levels of 3-NT, it is evident that oxidation causes mitochondrial dysfunction, and eventually leads to cognitive dysfunction,” said Dr. Fukui.
The results could help in promoting ways to prevent ROS, such as taking in vitamin E and C, which have an antioxidant effect.
The study is published in the journal Biomedicines.
