TL;DR
Researchers at Case Western Reserve, University Hospitals and the Cleveland VA report that restoring brain NAD+ balance prevented and reversed Alzheimer-type pathology and cognitive deficits in two different mouse models. The team used the experimental agent P7C3-A20, observed normalization of plasma p-tau217, and found accelerated NAD+ decline in human AD brain samples, but human trials have not yet been conducted.
What happened
A multi-institution research team tested whether re-establishing cellular energy balance in the brain could not only slow but reverse advanced Alzheimer-like disease in laboratory animals. Published Dec. 22 in Cell Reports Medicine, the study combined analysis of human Alzheimer’s brain tissue with experiments in two genetically engineered mouse lines—one carrying multiple human amyloid-processing mutations and another with a human tau mutation. Investigators found a marked decline in brain NAD+ in human AD samples and in both mouse models. Administering P7C3-A20, a pharmacologic agent developed in the Pieper laboratory that helps cells maintain NAD+ balance, prevented disease when given early and, strikingly, reversed pathology and restored cognitive performance when given after disease was established. Recovery was accompanied by normalization of blood phosphorylated tau 217, a clinical biomarker. The authors note prior work with P7C3-A20 in traumatic brain injury and urge careful translation into human trials.
Why it matters
- Challenges the long-standing view that Alzheimer’s disease is irreversible and shifts focus toward possible recovery strategies.
- Identifies brain NAD+ balance as a potential therapeutic target that can affect both pathology and function in animal models.
- Provides an objective biomarker—plasma phosphorylated tau 217—that tracked recovery in treated animals and could inform clinical studies.
- Highlights safety and translational questions, including differences between targeted pharmacologic NAD+ modulation and over-the-counter NAD+ precursors.
Key facts
- Study published Dec. 22 in Cell Reports Medicine by researchers at Case Western Reserve University, University Hospitals and the Louis Stokes Cleveland VA Medical Center.
- Human Alzheimer’s brain samples and two mouse models showed pronounced declines in the cellular energy molecule NAD+.
- Mouse models included one with multiple human amyloid-processing mutations and another with a human tau mutation, both developing Alzheimer-like pathology and cognitive deficits.
- Treatment used P7C3-A20, a pharmacologic agent from the Pieper lab that helps cells maintain NAD+ balance under stress.
- Preserving NAD+ prevented disease onset in mice; delayed treatment in animals with advanced disease reversed major pathological events and restored cognition.
- Blood levels of phosphorylated tau 217 (p-tau217) normalized after treatment in mice, aligning an objective biomarker with functional recovery.
- Authors reference prior PNAS work showing NAD+ restoration aided recovery after severe traumatic brain injury.
- Study team cautions that over-the-counter NAD+ precursors have raised cellular NAD+ to supraphysiologic levels in animals and been associated with increased cancer risk, whereas P7C3-A20 maintains balance without excessive elevation.
- The therapeutic approach is being commercialized by Glengary Brain Health, a company co-founded by senior author Andrew Pieper.
What to watch next
- Carefully designed human clinical trials to test whether NAD+ balance restoration translates to patients with Alzheimer’s disease.
- Safety and dosing comparisons between targeted agents like P7C3-A20 and over-the-counter NAD+ precursors.
- Laboratory follow-up to identify which elements of brain energy metabolism are critical for recovery and whether complementary approaches enhance outcomes.
Quick glossary
- NAD+: A central cellular coenzyme involved in metabolism and energy production; levels decline with age and under stress.
- Amyloid pathology: Accumulation of misprocessed amyloid proteins in the brain, historically linked to Alzheimer’s disease.
- Tau pathology: Abnormal modification and aggregation of the tau protein, which can disrupt neuronal structure and function.
- p-tau217: A phosphorylated form of the tau protein measured in blood that serves as a clinical biomarker for Alzheimer’s disease.
- P7C3-A20: An experimental pharmacologic compound developed in the Pieper lab that supports cellular NAD+ balance under stress.
Reader FAQ
Does this study show Alzheimer’s can be reversed in people?
Not confirmed in the source; the study demonstrated reversal in mouse models and analyzed human brain tissue for NAD+ decline, but human therapeutic efficacy has not been established.
Is P7C3-A20 an approved treatment?
Not confirmed in the source; the paper describes P7C3-A20 as an experimental pharmacologic agent developed in the researchers' lab.
Are over-the-counter NAD+ supplements a safe alternative?
The source reports that OTC NAD+ precursors have raised NAD+ to supraphysiologic levels in animal studies and been linked to cancer risk, so clinicians should exercise caution.
What are the next research steps?
The authors call for human clinical trials, studies to pinpoint which aspects of brain energy balance drive recovery, and investigation of complementary approaches and other neurodegenerative diseases.
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 …
- Pharmacologic reversal of advanced Alzheimer's disease …
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