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Scientists may have pinpointed a way to reverse Alzheimer’s disease in an animal study.
The study, led by University Hospitals Cleveland Medical Center, found that restoring a central cellular energy molecule in mice’s brains reversed the markers of the disease, including brain changes and cognitive decline.
Researchers analyzed two Alzheimer’s mouse models — as well as human Alzheimer’s brain tissue — and found severe levels of NAD+ decline.
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NAD+, an enzyme that is essential for energy production, cell maintenance and long-term cell health, naturally declines with age, according to senior study author Andrew A. Pieper, M.D., Ph.D., director of the Brain Health Medicines Center at Harrington Discovery Institute at University Hospitals in Cleveland, Ohio.
“When NAD+ falls below necessary levels, cells cannot effectively perform essential maintenance and survival functions,” he told Fox News Digital.
Dr. Charles Brenner, chief scientific advisor for Niagen, which specializes in products that boost NAD+ levels, shared that NAD+ plays a significant role in powering organs that require high energy, including the brain.
“The brain consumes around 20% of your body’s energy and has high demand for NAD+ for cellular energy production and DNA repair,” Brenner, who was not involved in the study, told Fox News Digital. “This is because NAD+ plays a key role in the way that neurons adapt to a range of physiological stressors and support processes associated with brain health.”
“Our experiments provide a proof of principle that some forms of dementia may not be inevitably permanent.”
Research demonstrates the potential benefits of NAD+ supplementation in brain health conditions such as Alzheimer’s disease, Parkinson’s disease and ataxia telangiectasia, he added.
In the UH Cleveland study, researchers used a medication called P7C3-A20 to restore normal levels of NAD+ in mice models, which was found to block the onset of Alzheimer’s. In brains with advanced Alzheimer’s, it reversed amyloid and tau build-up and fully restored cognitive function, according to the researchers.
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Treated mice also showed normalized blood levels of phosphorylated tau 217, an important clinical biomarker used in human Alzheimer’s research.
“For more than a century, Alzheimer’s has been considered irreversible,” Pieper said. “Our experiments provide a proof of principle that some forms of dementia may not be inevitably permanent.”
The researchers were “struck” by how robustly the advanced Alzheimer’s was reversed in mice’s brains 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,” Pieper added.
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This work builds on previous research from the lab demonstrating that restoring NAD+ balance helped to speed recovery after severe traumatic brain injury.
The study — which was conducted along with Case Western Reserve University and the Louis Stokes Cleveland VA Medical Center — was published last week in the journal Cell Reports Medicine.
Risks and limitations
The main limitation of the study is that it was only conducted in mouse models and may not directly translate to the disease in humans, according to the researchers.
“Alzheimer’s is a complex, multifactorial, uniquely human disease,” Pieper told Fox News Digital. “Efficacy in animal models does not guarantee the same results in human patients.”
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While drugs have been tested in clinical trials with the goal of slowing Alzheimer’s progression, none have been tested for reversal in humans.
The authors also warned that over-the-counter NAD+-boosting supplements can raise cellular NAD+ to excessively high levels that, in some animal models, have been shown to promote cancer.
“P7C3-A20, by contrast, enables cells to restore and preserve appropriate NAD+ balance under stress without driving NAD+ to excessively high levels,” Pieper noted.
Anyone considering NAD+-modulating supplements should discuss the risks and benefits with their physician, he recommended.
There are also proven lifestyle measures that promote brain resilience, according to the researcher.
“Alzheimer’s is a complex, multifactorial, uniquely human disease.”
“These include prioritizing sufficient sleep, following a MIND or Mediterranean diet, staying cognitively and physically active, maintaining social connections, addressing hearing loss, protecting your head from physical injury, limiting alcohol, and controlling blood pressure and other cardiovascular risk factors like avoiding smoking,” Pieper advised.
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Looking ahead, the team plans to conduct further research into the impact of brain energy balance on cognitive health, and to test whether the strategy works for other age-related neurodegenerative diseases.
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