CLEVELAND, Jan 21: Researchers in Cleveland have successfully reversed advanced Alzheimer’s disease in mice, achieving full cognitive recovery and offering new hope for dementia patients.

A joint study by University Hospitals, Case Western Reserve University, and the Cleveland VA shows that restoring the brain’s energy balance can repair damage caused by Alzheimer’s, challenging the century-long belief that the disease is irreversible.

Dr. Andrew Pieper, director of the Brain Health Medicines Center at University Hospitals and senior author of the study, described the findings as a “fundamental shift” in understanding Alzheimer’s. “The key takeaway is a message of hope – the effects of Alzheimer’s disease may not be inevitably permanent,” he said. “The damaged brain can, under some conditions, repair itself and regain function.”

Published in Cell Reports Medicine, the research focuses on NAD+, a cellular energy molecule that naturally declines with age and drops sharply in Alzheimer’s-affected brains. Using a compound called P7C3-A20, developed in Pieper’s lab, researchers stabilized NAD+ levels in two mouse models, halting disease progression and restoring cognitive function.

The approach is independent of amyloid-targeting therapies currently used for Alzheimer’s treatment. “It could work on its own, potentially, and may also complement any therapy being given to people,” Pieper said.

Unlike over-the-counter NAD+ supplements, the compound maintains normal cellular NAD+ levels without overproduction, enhancing safety. Pieper compared NAD+ to a car’s gas tank: when full, the brain can respond to increased demands; when depleted, it becomes vulnerable to disease. “If we can keep the energy levels stable, the brain is always equipped to fight off these insults and fight off the disease,” he said.

The research team has formed Glengary Brain Health to prepare for human trials. While the compound has been safe in year-long monkey studies, it requires chemical modifications before human testing. Pieper hopes to begin phase one safety trials within approximately 18 months.

He noted that the approach may extend beyond Alzheimer’s to other neurodegenerative conditions and dementia, including traumatic brain injury. “We view Alzheimer’s as the biggest problem. It’s an emergency, if you will, for our species,” he said.

Pieper cautioned that success in mice does not guarantee similar results in humans. “Alzheimer’s is a uniquely human condition, and we do our best to model it in mice. There is no guarantee that what works in mice works in people,” he said. He also suggested that treatment should start early for those at risk, based on animal model findings.

Meanwhile, Pieper emphasized lifestyle factors that promote brain health, including adequate sleep, Mediterranean or MIND diets, blood pressure control, moderate exercise, and social engagement. “When we sleep, our brain clears out its toxins and rejuvenates,” he said, adding that managing metabolic health is critical to maintaining brain function.

He also addressed the strain on caregivers. “Alzheimer’s and related diseases affect not just the patient, but everyone caring for them. It can be very draining. Caregivers need to take care of their own physical and mental health,” he said, recommending support resources like Hilarity for Charity, founded by comedian Seth Rogen.

Pieper described the study as a major departure from traditional Alzheimer’s research. “This is the first time anybody’s ever shown that the brain can recover from an advanced dementia-like disease,” he said. “We’re really excited about what we found, and others are also working on complementary approaches.”