Restoring brain energy helped reverse Alzheimer’s damage in advanced mouse studies.
For more than one hundred years, Alzheimer’s disease has been treated as a one-way path. Once memory and thinking begin to fail, the damage has been thought to be permanent. Because of this belief, most research has focused on slowing the illness or trying to stop it before it starts, rather than helping the brain recover after the disease is well underway. Despite many years of work and large amounts of funding, no drug trial has been built around the idea that lost brain function could return. A new study from researchers connected to University Hospitals in Cleveland challenges that long-standing belief. The research explored whether brains already showing severe signs of Alzheimer’s could regain normal function. Instead of focusing only on plaques or tangles, the team looked at how brain cells manage energy. The findings suggest that restoring balance to a key energy system in the brain can reverse many signs of the disease in animal models.
At the center of the study is a molecule called NAD+, which plays a basic role in how cells make and use energy. NAD+ is needed for cells to repair damage, communicate, and stay alive under stress. As people grow older, levels of this molecule drop throughout the body, including in the brain. When levels fall too low, cells struggle to carry out daily tasks and may die.
The research team found that this drop is far worse in brains affected by Alzheimer’s. By examining donated human brain tissue and comparing it with healthy samples, the researchers saw a clear pattern of reduced NAD+ in areas tied to memory and thinking. The same pattern appeared in laboratory mice designed to develop Alzheimer’s-like disease.
To study this problem more closely, two different mouse models were used. One group carried human gene changes linked to amyloid buildup, while the other carried a gene change tied to tau protein problems. These two issues are known to play early roles in Alzheimer’s. Over time, both types of mice developed many features seen in people with the disease. These included damage to nerve fibers, swelling and irritation in the brain, trouble forming new brain cells, weak connections between neurons, and serious memory problems.
After confirming that brain energy levels were low in both mouse groups, the researchers tested whether correcting this imbalance could change the course of the disease. Some mice received treatment before symptoms appeared, while others were treated after the disease was advanced. The treatment used a lab-developed drug designed to help brain cells keep NAD+ at healthy levels during stress.
The results were striking. Mice that received early treatment did not develop many of the usual brain problems tied to Alzheimer’s. Even more surprising, mice that already showed major damage improved after treatment began. Brain structure improved, signs of swelling dropped, and nerve connections strengthened. Most importantly, the mice regained normal performance on memory tests.
Blood tests from the treated mice also showed improvement in a marker linked to Alzheimer’s in people. Levels of a form of tau protein that rises during the disease returned to normal. This finding matters because it suggests an easy way to track recovery in future human studies.
The researchers stressed that this approach is different from taking common supplements sold to boost NAD+ levels. Past studies have shown that forcing NAD+ too high can be risky and may support cancer growth. The drug used in this study does not flood cells with energy molecules. Instead, it helps cells hold steady levels when under heavy strain.
The findings change how Alzheimer’s may be viewed in the future. Rather than seeing the disease as permanent damage, the study suggests that at least some brain injury may be repaired if energy balance is restored. While these results come from animal models and not people, they open the door to new types of clinical trials focused on recovery, not just slowing decline.
Further research is planned to test whether similar benefits appear in human patients and to learn which parts of brain energy control matter most. The work also raises questions about whether the same strategy could help other age-related brain diseases. For patients and families facing Alzheimer’s, the study offers a new line of thinking: the damaged brain may have more ability to heal than once believed.
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Restoring brain energy balance reverses Alzheimer’s disease in mouse models
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