TL;DR
Researchers report that correcting a decline in the cellular energy molecule NAD+ restored brain structure and function in two different mouse models of advanced Alzheimer’s disease. Treatment with the experimental compound P7C3-A20 prevented disease when given early and reversed pathology and cognitive deficits when given later; the work was published Dec. 22 in Cell Reports Medicine.
What happened
A team from Case Western Reserve University, University Hospitals and the Cleveland VA investigated whether advanced Alzheimer’s-like disease could be reversed in laboratory animals. They analyzed human AD brain tissue and two genetically engineered mouse lines that model amyloid- and tau-driven pathology, finding a pronounced drop in the central energy cofactor NAD+ in affected brains. Using the investigational molecule P7C3-A20, developed in the Pieper laboratory, researchers maintained cellular NAD+ balance and observed that treated animals were protected from developing disease and, strikingly, that mice with established pathology regained normal brain markers and behavioral performance. Blood levels of phosphorylated tau 217, a clinical biomarker, returned to normal alongside functional recovery. The authors caution against equating over-the-counter NAD+ precursors with this pharmacologic approach, noting prior evidence that indiscriminate NAD+ elevation can have harmful effects in animals. The team calls for further mechanistic studies and carefully designed human trials.
Why it matters
- Challenges the long-standing view that Alzheimer’s disease is irreversible by demonstrating recovery in animal models.
- Identifies NAD+ balance as a potentially central metabolic target for preventing and reversing neurodegeneration.
- Shows a circulating clinical biomarker (phosphorylated tau 217) tracked with recovery, offering an objective measure for future trials.
- Highlights safety considerations around simple NAD+ boosting supplements versus controlled pharmacologic strategies.
Key facts
- Study published online Dec. 22 in Cell Reports Medicine.
- Research led by investigators at Case Western Reserve, University Hospitals and the Louis Stokes Cleveland VA Medical Center.
- Investigators examined NAD+ decline in both human Alzheimer’s brains and two mouse models (one with multiple human amyloid-processing mutations, one with a human tau mutation).
- Treatment used the experimental compound P7C3-A20 to preserve or restore cellular NAD+ balance.
- In treated mice, pathological hallmarks (including blood–brain barrier deterioration, axonal degeneration and neuroinflammation) were ameliorated and cognitive function recovered.
- Blood levels of phosphorylated tau 217 normalized in animals that regained cognitive performance.
- Authors warn that over-the-counter NAD+ precursors have, in animal studies, been linked to dangerously high NAD+ and cancer risk, distinguishing the study drug’s balancing mechanism.
- The technology is being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by the study’s senior author.
- Authors state the next steps include identifying which aspects of brain energy balance drive recovery and testing the approach in human clinical trials.
What to watch next
- Whether and when carefully designed human clinical trials of the NAD+-restoring approach are initiated — not confirmed in the source.
- Laboratory efforts to pinpoint which components of cellular energy balance are essential for the observed recovery (confirmed as a next step).
- Progress of Glengary Brain Health in translating the laboratory technology toward clinical development (commercialization in progress per the source).
- Clinical biomarker work to validate phosphorylated tau 217 as an objective indicator of recovery in future human studies (implied in the study).
Quick glossary
- NAD+: Nicotinamide adenine dinucleotide, a cellular cofactor involved in energy metabolism and many biochemical reactions; levels decline with age.
- Amyloid: Protein fragments that can accumulate into plaques in the brain; amyloid pathology is associated with Alzheimer’s disease.
- Tau: A neuronal protein that can become abnormally modified and aggregate into tangles in Alzheimer’s disease and related disorders.
- Phosphorylated tau 217 (p-tau217): A blood- and cerebrospinal-fluid-detectable form of tau used as a biomarker that can reflect Alzheimer’s disease-related brain changes.
Reader FAQ
Does this study prove Alzheimer’s can be reversed in people?
Not confirmed in the source. The findings are limited to mouse models and analysis of human tissue; human clinical efficacy has not been demonstrated.
Is the compound P7C3-A20 available for patients?
Not confirmed in the source. The compound is an investigational agent used in laboratory studies; human safety and approval status are not reported.
Can over-the-counter NAD+ supplements reproduce these results?
The source warns against equating OTC NAD+ precursors with the study drug, noting animal evidence that indiscriminate NAD+ elevation can promote cancer risk; the study used a pharmacologic agent designed to maintain proper NAD+ balance.
What are the next steps reported by the researchers?
They call for mechanistic lab work and carefully designed human clinical trials to determine whether the animal results translate to people.
New study shows Alzheimer’s disease can be reversed to achieve full neurological recovery—not just prevented or slowed—in animal models Researchers from Case Western Reserve University, University Hospitals and the Cleveland…
Sources
- Alzheimer’s disease can be reversed in animal models: Study
- Scientists reverse Alzheimer's in mice and restore memory
- New study shows Alzheimer's disease can be reversed in …
- Scientists reverse Alzheimer's in mice using nanoparticles
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