A study from University Hospitals suggests that restoring the brain’s energy molecule NAD+ may reverse Alzheimer’s disease in animal models, offering hope for future human applications.
A promising new method for reversing Alzheimer’s disease has emerged from research conducted at University Hospitals Cleveland Medical Center. The study reveals that restoring a central cellular energy molecule known as NAD+ in the brains of mice has the potential to reverse key markers of the disease, including cognitive decline and brain changes.
Researchers analyzed two different mouse models of Alzheimer’s, along with human brain tissue affected by the disease. They discovered significant declines in NAD+ levels, which is crucial for energy production, cell maintenance, and overall cell health. According to Dr. Andrew A. Pieper, the senior author of the study and director of the Brain Health Medicines Center at Harrington Discovery Institute, the decline of NAD+ is a natural part of aging.
“When NAD+ falls below necessary levels, cells cannot effectively perform essential maintenance and survival functions,” Dr. Pieper explained in an interview.
Dr. Charles Brenner, chief scientific advisor for Niagen, a company specializing in products that enhance NAD+ levels, emphasized the importance of this molecule. He noted that the brain consumes approximately 20% of the body’s energy and has a high demand for NAD+ to support cellular energy production and DNA repair. “NAD+ plays a key role in how neurons adapt to various physiological stressors and supports processes associated with brain health,” he stated.
The study utilized a medication called P7C3-A20 to restore normal NAD+ levels in the mouse models. Remarkably, this treatment not only blocked the onset of Alzheimer’s but also reversed the accumulation of amyloid and tau proteins in the brains of mice with advanced stages of the disease. Researchers reported a full restoration of cognitive function in these treated mice.
Additionally, the treated mice exhibited normalized blood levels of phosphorylated tau 217, a significant clinical biomarker used in human Alzheimer’s research. Dr. Pieper remarked, “For more than a century, Alzheimer’s has been considered irreversible. Our experiments provide proof of principle that some forms of dementia may not be inevitably permanent.”
The researchers were particularly impressed by the extent to which advanced Alzheimer’s was reversed in the mice when NAD+ homeostasis was restored, even without directly targeting amyloid plaques. “This gives reason for cautious optimism that similar strategies may one day benefit people,” Dr. Pieper added.
This research builds on previous findings from the lab, which demonstrated that restoring NAD+ balance could accelerate recovery following severe traumatic brain injury. The study, conducted in collaboration with Case Western Reserve University and the Louis Stokes Cleveland VA Medical Center, was published last week in the journal Cell Reports Medicine.
However, the researchers caution that the study’s findings are limited to mouse models and may not directly translate to human patients. “Alzheimer’s is a complex, multifactorial, uniquely human disease,” Dr. Pieper noted. “Efficacy in animal models does not guarantee the same results in human patients.”
While various drugs have been tested in clinical trials aimed at slowing the progression of Alzheimer’s, none have been evaluated for their potential to reverse the disease in humans. The authors also warned that over-the-counter NAD+-boosting supplements can lead to excessively high cellular NAD+ levels, which have been linked to cancer in some animal studies. Dr. Pieper explained that P7C3-A20 allows cells to restore and maintain appropriate NAD+ balance under stress without pushing levels too high.
For those considering NAD+-modulating supplements, Dr. Pieper recommends discussing the risks and benefits with a physician. He also highlighted proven lifestyle strategies that can promote brain resilience, including prioritizing sufficient sleep, following a MIND or Mediterranean diet, staying cognitively and physically active, maintaining social connections, addressing hearing loss, protecting against head injuries, limiting alcohol consumption, and managing cardiovascular risk factors such as avoiding smoking.
Looking ahead, the research team plans to further investigate the impact of brain energy balance on cognitive health and explore whether this strategy can be effective for other age-related neurodegenerative diseases, according to Fox News.