This is the latest saga in AD, which I have been following since at least 2012 when the first study with niacinamide reversing AD in mice was published. After that study, a human study was apparently initiated at UCLA, using 3g niacinamide daily, which was the human-equivalent dose of the mouse study. The human study appears to be still ongoing, with some of the study arms completed. However, so far no results have been published. I suspect the reason for the radio silence is that if news broke that niacinamide cured AD would probably be the end of Big Pharma for good. Not only is niacinamide dirt cheap, over-the-counter (OTC), and virtually risk-free (up to 3g daily), but the fact that AD is a metabolic disease would reverberate and permeate across the entire “disease space” that keeps Big Pharma in business. Namely, since the original 2012 study with AD, there has been a ton of publications linking low NAD+ levels to virtually every chronic condition we know of, thus not only implicating all of them as metabolic in origin, but also suggesting dirt cheap, OTC remedies can cure them. A nightmare for Big Pharma indeed! Perhaps due to those implications, the study below took a slightly different approach. Instead of boosting NAD+ levels using precursors such as niacinamide, the study used a patented drug (P7C3-A20) that boosts the activity of the enzyme NAMPT, which is the rate-limiting enzyme in synthesizing NAD+ from precursors such as niacinamide. So, basically the same effect as giving niacinamide, but using a patented drug that gives Big Pharma the opportunity to monetize the now-inevitable conversion of (fully failed) AD treatments from structural (removing amyloid plaque) to functional/metabolic. Finally, it is worth pointing out that the study did not simply “ameliorate” the symptoms of AD in mice, as many other studies have done. It actually fully reversed advanced AD structural pathology and symptoms by boosting NAD+ levels.
https://pubmed.ncbi.nlm.nih.gov/41435831/
Alzheimer’s Reversed in Mice by Boosting NAD+ Levels, Study Shows
“…Now, a groundbreaking study from researchers at Case Western Reserve University School of Medicine is challenging this paradigm, demonstrating in animal models that Alzheimer’s can not only be halted but fully reversed, restoring neurological function to pre-disease levels. By targeting the brain’s energy metabolism—specifically, the molecule nicotinamide adenine dinucleotide (NAD+)—scientists have achieved what was once thought impossible: complete recovery from advanced stages of the disease in mice. The study, published in the Proceedings of the National Academy of Sciences, builds on years of investigation into metabolic failures in the brain. Led by Jonathan Haines, chair of the Department of Population and Quantitative Health Sciences at Case Western Reserve, and co-authored by researchers from University Hospitals and the Louis Stokes Cleveland VA Medical Center, the work reveals that Alzheimer’s is driven in part by a catastrophic drop in NAD+ levels. This coenzyme is crucial for cellular energy production, DNA repair, and overall brain health. When NAD+ depletes, neurons suffer oxidative stress, inflammation, and the accumulation of toxic proteins like amyloid-beta and tau, hallmarks of Alzheimer’s pathology. In experiments with multiple mouse models engineered to mimic human Alzheimer’s, the team administered compounds to boost NAD+ levels. The results were striking: not only did the treatment prevent further decline, but it also repaired existing damage. Mice with severe cognitive impairments regained memory function, normalized biomarkers, and showed reversal of brain pathology, including reduced plaques and tangles. As Haines explained in the university’s announcement, “This is the first time we’ve shown that restoring NAD+ can lead to full neurological recovery, even in late-stage disease.”
“…Delving deeper into the mechanism, the researchers analyzed both mouse brains and postmortem human Alzheimer’s tissue. They found consistent evidence of NAD+ dysregulation, where the brain’s inability to maintain energy balance exacerbates neuronal death. NAD+ acts as a linchpin in mitochondrial function, and its decline creates a vicious cycle: impaired energy production leads to more protein misfolding, which further depletes NAD+. By intervening with NAD+ precursors like nicotinamide riboside or other boosters, the study interrupted this cycle, allowing the brain to self-repair. This approach differs markedly from current therapies, which primarily target amyloid plaques. Drugs like those approved by the FDA focus on clearing these proteins but often come with side effects such as brain swelling and bleeding, and they don’t restore lost function. In contrast, the NAD+ strategy addresses a root cause—energy failure—potentially offering a safer, more comprehensive solution. The study’s co-author, Dr. Andrew Pieper from the Harrington Discovery Institute at University Hospitals, noted that “restoring metabolic balance could be key to treating not just Alzheimer’s but other neurodegenerative diseases.”
