Alzheimer’s Damage May Be Reversible: Suggests New Study 


For decades, Alzheimer’s disease (AD) has been viewed as an irreversible condition. Most research has focused on slowing or preventing the disease, not reversing it. Despite years of effort and massive investment, no drug has ever been tested in humans to restore brain function after advanced Alzheimer’s.

A new study by researchers from Case Western Reserve University, University Hospitals, and the Louis Stokes Cleveland VA Medical Centre is now challenging that belief.

Published on December 22 in Cell Reports Medicine, the study explored whether brains already severely affected by Alzheimer’s could recover. The research was led by Kalyani Chaubey from the Pieper Laboratory.

What the Study Found

The team discovered that a major driver of Alzheimer’s is the brain’s inability to maintain healthy levels of NAD+, a molecule essential for cellular energy and survival. NAD+ levels naturally decline with age, but the study found that this decline is much more severe in people with Alzheimer’s—and in mouse models of the disease.

Using two genetically engineered mouse models that mimic human Alzheimer’s (one linked to amyloid and the other to tau protein), researchers observed hallmark features of advanced disease, including brain inflammation, nerve damage, memory loss, and cognitive decline.

Reversing Advanced Disease in Mice

The researchers tested whether restoring NAD+ balance could help—not only before disease onset, but even after Alzheimer’s had significantly progressed. They used a drug called P7C3-A20, previously shown to protect brain cells after severe traumatic brain injury.

Remarkably, mice treated after developing advanced Alzheimer’s showed reversal of brain pathology and full recovery of cognitive function. Blood levels of phosphorylated tau-217—a clinical biomarker used in humans—also returned to normal, supporting true disease reversal.

Why This Matters

Senior author Andrew A. Pieper said the findings offer hope that Alzheimer’s damage may not be permanent.

“The key takeaway is a message of hope—the damaged brain can, under some conditions, repair itself and regain function,” he said.

The researchers caution against using over-the-counter NAD+ supplements, which can raise NAD+ to unsafe levels and increase cancer risk in animals. In contrast, P7C3-A20 helps cells maintain normal NAD+ balance without excess.

What Comes Next

While the results are limited to animal models, the study represents a major shift in thinking. The approach is now being prepared for future human clinical trials through the Cleveland-based company Glengary Brain Health.

Researchers stress that carefully designed trials are needed to determine whether similar recovery is possible in people with Alzheimer’s.