Scientists Reverse Alzheimer’s in Mice, Restoring Memory

For more than a century, Alzheimer’s disease has been regarded as an irreversible condition—a slow, one-way decline of memory and cognition. But groundbreaking new research from University Hospitals Cleveland Medical Center and Case Western Reserve University challenges that long-held belief, showing that recovery may actually be possible.

A New Understanding of Alzheimer’s

The study, published in Cell Reports Medicine on December 22, 2025, reveals that Alzheimer’s is driven in part by a collapse in the brain’s energy balance. Specifically, researchers identified a sharp decline in NAD⁺, a vital cellular energy molecule, as a key factor in the disease. NAD⁺ naturally decreases with age, but the drop is far more severe in Alzheimer’s patients.

By restoring NAD⁺ balance in mouse models of Alzheimer’s, scientists were able not only to prevent the disease but also to reverse its effects—even in advanced stages. Mice regained normal brain function, repaired damaged neural pathways, and recovered memory performance.

How the Study Was Conducted

Researchers tested two engineered mouse models carrying human genetic mutations linked to Alzheimer’s: one affecting amyloid processing and another involving tau protein. Both models developed severe brain pathology, including inflammation, oxidative damage, and memory loss.

Treatment with a pharmacologic compound called P7C3-A20, developed in the Pieper Laboratory, successfully restored NAD⁺ balance. Remarkably, even mice with advanced Alzheimer’s showed full cognitive recovery. Blood tests confirmed normalized levels of phosphorylated tau 217, a biomarker used to diagnose Alzheimer’s in humans.

Why This Matters

This discovery represents a paradigm shift in how Alzheimer’s could be treated. Instead of focusing solely on slowing decline, therapies may one day aim for true recovery of brain function. Senior author Dr. Andrew A. Pieper emphasized the hopeful message: “The damaged brain can, under some conditions, repair itself and regain function.”

Importantly, the researchers caution against confusing this approach with over-the-counter NAD⁺ supplements, which can raise levels dangerously high and even promote cancer. The compound used in the study works differently, maintaining healthy NAD⁺ balance without exceeding safe limits.

Next Steps

The findings open the door to carefully designed human clinical trials. Researchers plan to investigate which aspects of brain energy balance are most critical, explore complementary strategies, and test whether similar recovery is possible in other age-related neurodegenerative diseases.

If successful, this line of research could transform Alzheimer’s treatment from managing decline to enabling meaningful recovery—a possibility once thought unimaginable.

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Source: University Hospitals Cleveland Medical Center. “Scientists reverse Alzheimer’s in mice and restore memory.” ScienceDaily, December 24, 2025. Read the original report.

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