Daijiworld Media Network - Washington

Washington, Dec 26: In a scientific breakthrough that challenges long-held beliefs about Alzheimer’s disease, researchers have demonstrated that restoring the brain’s energy balance can reverse disease-related damage and fully restore memory, even at advanced stages — at least in mouse models.

The study, published on December 22 in Cell Reports Medicine, found that severe depletion of nicotinamide adenine dinucleotide (NAD?) — a molecule vital for cellular energy — plays a central role in driving Alzheimer’s disease. Restoring NAD? balance repaired brain damage, normalised disease biomarkers and reversed cognitive decline in mice.

For more than a century, Alzheimer’s has largely been considered irreversible, with most research focused on prevention or slowing progression. The new findings suggest that even damaged brains may retain the ability to repair themselves under the right conditions.

The research was led by Dr Kalyani Chaubey of the Pieper Laboratory, with collaborators from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center.

By analysing human Alzheimer’s brain tissue and multiple genetically engineered mouse models, researchers found that NAD? levels decline far more sharply in Alzheimer’s brains than in normal ageing. This depletion disrupts critical cellular processes and contributes to widespread neurological damage.

To test whether this damage could be reversed, the team treated mice with P7C3-A20, a pharmacological compound developed in the Pieper Laboratory that helps maintain healthy NAD? levels during cellular stress.

The results were striking. Even mice treated after developing advanced Alzheimer’s pathology showed significant repair of brain damage, including reduced inflammation, restoration of nerve fibres, and improved neuron communication. Both amyloid- and tau-based models demonstrated complete recovery of learning and memory.

Blood tests further showed normalised levels of phosphorylated tau-217, a clinically approved biomarker used in diagnosing Alzheimer’s in humans, strengthening evidence of disease reversal.

“We were very excited and encouraged by our results,” said senior author Dr Andrew A. Pieper, Director of the Brain Health Medicines Center at University Hospitals. “Restoring the brain’s energy balance achieved both pathological and functional recovery in mice with advanced Alzheimer’s.”

Dr Pieper cautioned against equating the treatment with over-the-counter NAD? supplements, warning that such products can raise NAD? levels beyond safe limits and have been linked to cancer risk in animal studies. The compound used in the study restores balance without exceeding normal levels.

“The key takeaway is a message of hope,” Pieper said. “The effects of Alzheimer’s disease may not be inevitably permanent.”

While the findings are currently limited to animal studies, researchers said the work opens the door for future human clinical trials. The technology is being commercialised by Cleveland-based Glengary Brain Health.