TL;DR
Researchers report that correcting brain NAD+ imbalance with a pharmacologic agent reversed pathological and cognitive features of advanced Alzheimer’s in two mouse models. The work—published in Cell Reports Medicine—identifies NAD+ decline as a major driver of disease and highlights a biomarker (phosphorylated tau 217) for tracking recovery, while urging careful clinical testing.
What happened
A team from Case Western Reserve University, University Hospitals and the Cleveland VA tested whether restoring cellular energy balance in the brain could prevent or reverse Alzheimer’s disease (AD) in animal models. They analyzed human AD brain tissue and found pronounced declines in the cellular energy molecule NAD+. Using two genetically engineered mouse lines that model amyloid and tau-driven AD, the researchers treated animals with a pharmacologic compound (P7C3-A20) developed in the Pieper lab. Preventive dosing blocked disease development; importantly, delayed dosing in mice with advanced pathology led to repair of multiple disease features and full recovery of cognitive performance. Treated animals also showed normalization of blood levels of phosphorylated tau 217, a clinical AD biomarker. The authors caution against over-the-counter NAD+ precursors and call for carefully designed human trials to evaluate whether the approach translates to patients.
Why it matters
- Challenges longstanding view that Alzheimer’s is inevitably irreversible by demonstrating recovery in animal models.
- Identifies NAD+ decline as a potentially central, addressable driver of AD pathology.
- Provides an objective biomarker (p-tau217) that correlated with recovery and could be used in future trials.
- Suggests a therapeutic avenue distinct from current prevention- and slowing-focused strategies, prompting further translational work.
Key facts
- The study was published online Dec. 22, 2025, in Cell Reports Medicine.
- Researchers analyzed human AD brain tissue and observed pronounced declines in NAD+ compared with aging alone.
- Two independent mouse models were used: one with multiple human amyloid-processing mutations and one with a human tau mutation.
- The pharmacologic agent P7C3-A20, developed in the Pieper laboratory, was used to preserve or restore NAD+ balance.
- Preventive treatment blocked disease development; delayed treatment in advanced-stage mice reversed pathology and restored cognition.
- Blood levels of phosphorylated tau 217 normalized after treatment, providing an objective marker of reversal in mice.
- Authors note prior work showing P7C3-A20 repaired pathology after severe traumatic brain injury in animals.
- The paper warns that over-the-counter NAD+ precursor supplements have raised NAD+ to potentially harmful levels in animal studies.
- The technology is being commercialized by Glengary Brain Health, a company co-founded by the study’s senior author.
What to watch next
- Carefully designed human clinical trials to test whether P7C3-A20 or related approaches translate to patients (timing and initiation not confirmed in the source).
- Laboratory research identifying which specific aspects of brain energy balance are essential for recovery.
- Safety studies comparing targeted pharmacologic NAD+ modulation with over-the-counter NAD+ precursors, given animal data on potential risks.
- Progress and regulatory steps from Glengary Brain Health around commercialization and clinical development (timelines not confirmed in the source).
Quick glossary
- NAD+: A cellular coenzyme involved in energy metabolism and many enzymatic reactions; levels decline with age.
- Amyloid: Protein fragments that can accumulate into plaques in the brain and are implicated in Alzheimer’s pathology.
- Tau protein: A neuronal protein that can become abnormally modified and form tangles associated with neurodegeneration.
- Phosphorylated tau 217 (p-tau217): A specific modified form of tau measurable in blood that serves as a clinical biomarker for Alzheimer’s disease.
Reader FAQ
Does this study prove Alzheimer’s can be reversed in people?
Not confirmed in the source. The findings show reversal in mouse models and prompt human trials but do not establish efficacy in people.
What compound was used to restore NAD+ balance?
The study used P7C3-A20, a pharmacologic agent developed in the Pieper laboratory.
Are over-the-counter NAD+ supplements a safe substitute?
The authors warn that OTC NAD+ precursors raised NAD+ to potentially dangerous levels that promoted cancer in animal studies; clinical safety in people is not confirmed in the source.
How did researchers measure recovery in the study?
Recovery was assessed by reversal of multiple pathological features in the brain, restoration of cognitive performance in mice, and normalization of blood phosphorylated tau 217.
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 can be reversed to achieve full neurological recovery in animals
- Scientists reverse Alzheimer's in mice and restore memory
- New study shows Alzheimer's disease can be reversed in …
- Study Shows Alzheimer's Disease Can Be Reversed in …
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