https://scitechdaily.com/scientists-found-a-way-to-help-the-brain-bounce-back-from-alzheimers/
For more than a hundred years, Alzheimer's disease (AD) has been regarded as a condition that cannot be undone. Because of this assumption, most scientific efforts have focused on stopping the disease before it starts or slowing its progression, rather than attempting to restore lost brain function. Despite decades of research and billions of dollars invested, no drug trial for Alzheimer's has ever been designed with the explicit goal of reversing the disease and restoring normal brain performance.
That long-standing belief is now being directly tested by researchers from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center. Their work asked a fundamental question that had rarely been explored: Can brains already damaged by advanced Alzheimer's recover?
The study was led by Kalyani Chaubey, PhD, of the Pieper Laboratory and was published on December 22 in Cell Reports Medicine. By analyzing multiple preclinical mouse models alongside brain tissue from people with Alzheimer's, the researchers identified a critical biological problem underlying the disease. They found that Alzheimer's is strongly driven by the brain's failure to maintain normal levels of a key cellular energy molecule called NAD+. Just as important, they showed that keeping NAD+ levels in balance can both prevent the disease and, under certain conditions, reverse it.
NAD+ naturally declines throughout the body as people age, including in the brain. When this balance is disrupted, cells gradually lose the ability to carry out essential processes needed for normal function and survival. The team found that this loss of NAD+ is far more pronounced in the brains of people with Alzheimer's. The same severe decline was also observed in mouse models of the disease.
[...] Amyloid buildup and tau abnormalities are among the earliest and most important features of Alzheimer's. In both mouse models, these mutations led to extensive brain damage that closely resembles the human condition. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and widespread oxidative damage. The mice also developed severe memory and thinking problems similar to those experienced by people with Alzheimer's.
After confirming that NAD+ levels drop sharply in both human and mouse Alzheimer's brains, the researchers explored two different strategies. They tested whether preserving NAD+ balance before symptoms appear could prevent Alzheimer's, and whether restoring NAD+ balance after the disease was already well established could reverse it.
[...] The results exceeded expectations. Maintaining healthy NAD+ levels prevented mice from developing Alzheimer's, but even more striking outcomes were seen when treatment began later. In mice with advanced disease, restoring NAD+ balance allowed the brain to repair major pathological damage caused by the genetic mutations.
Both mouse models showed complete recovery of cognitive function. This recovery was supported by blood tests showing normalized levels of phosphorylated tau 217, a recently approved clinical biomarker of Alzheimer's in people. These findings provided strong evidence that the disease process had been reversed and highlighted a potential biomarker for future clinical trials.
"We were very excited and encouraged by our results," said Andrew A. Pieper, MD, PhD, senior author of the study and Director of the Brain Health Medicines Center, Harrington Discovery Institute at UH. "Restoring the brain's energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer's. Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the idea that restoring the brain's NAD+ balance might help patients recover from Alzheimer's."
The findings suggest a major change in how Alzheimer's could be approached in the future. "The key takeaway is a message of hope – the effects of Alzheimer's disease may not be inevitably permanent," said Dr. Pieper. "The damaged brain can, under some conditions, repair itself and regain function."
[...] Dr. Pieper cautioned that this strategy should not be confused with over-the-counter NAD+-precursors. Studies in animals have shown that such supplements can raise NAD+ to dangerously high levels that promote cancer. The approach used in this research relies instead on P7C3-A20, which helps cells maintain a healthy NAD+ balance during extreme stress without pushing levels beyond their normal range.
Journal Reference: “Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain” by Kalyani Chaubey, Edwin Vázquez-Rosa, Sunil Jamuna Tripathi, et al., 22 December 2025, Cell Reports Medicine. DOI: 10.1016/j.xcrm.2025.102535
(Score: 1, Informative) by Anonymous Coward on Saturday January 10, @03:16AM
NAD+ = https://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide [wikipedia.org]
Long article, ianaoc (not an organic chemist), but it was discovered over a hundred years ago, during a study of yeast fermentation. One precursor in animals is tryptophan. The "dinucleotide" part of the name literally means that the structure is two nucleotides linked together.
(Score: 5, Informative) by ikanreed on Saturday January 10, @04:56AM (1 child)
Stephen Novella, the podcast's host and a long-time neurologist frequently mentions on the show that mouse models, while sort of reliable points of comparison for most drug development are notoriously disconnected from human results in Alzheimer's research. He cites major differences in human and mouse brain biochemistry, even with "humanified" mouse brains and the importance of age in the function of alzheimers. Apparently the hit-rate in humans for treatments successfully demonstrated in mice is less than 1%.
So this feels like one of those "Don't get your hopes up" news stories.
(Score: 3, Interesting) by spiraldancing on Saturday January 10, @06:47AM
Not disagreeing, and notably IANAD, but the specific substance they were testing, P7C3-A20 ( https://en.wikipedia.org/wiki/P7C3-A20 [wikipedia.org] ), seems to be effective in reversing a wide variety of neurological issues, including stroke, traumatic brain injury, optic nerve injury, neuropathy -- again, all in mice, but presumably different mice modeled to simulate different brain injuries, so it doesn't just cure the Alzheimer's mice. Still a long way from this to "we have a cure".
Lets go exploring.