Promising New Approach to Alzheimer's Treatment Shows Cognitive Restoration in Mice

A groundbreaking study from Case Western Reserve University has revealed a potential new avenue for treating Alzheimer's disease, offering hope for patients with advanced stages of the condition. Researchers have successfully demonstrated that restoring cellular energy levels can reverse cognitive decline in mouse models of Alzheimer's, potentially paving the way for a novel class of therapeutics.

NAD+ Deficiency Linked to Alzheimer's Severity

The study, published in Cell Reports Medicine on December 22, 2026, found a correlation between lower levels of nicotinamide adenine dinucleotide (NAD+) and increased severity of Alzheimer's disease in both human brain tissue and mouse models. NAD+ is a critical component of cellular metabolism, and its depletion appears to play a significant role in the progression of the disease.

Dr. Andrew Pieper, a neuroscientist at Case Western and senior author of the study, explained, "Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the new idea that recovery from advanced disease might be possible in people with AD when the brain's NAD+ balance is restored."

P7C3-A20: A Promising Compound for Cognitive Restoration

Researchers utilized a compound called P7C3-A20, designed to restore NAD+ to normal levels, in their experiments. The results were striking:

• P7C3-A20 prevented Alzheimer's from developing in mice
• The compound boosted memory and reduced anxiety in mice with advanced stages of the disease
• Therapeutic effects were observed in mouse models with two different genetic causes of Alzheimer's, one driven by amyloid protein and another by tau protein

Importantly, this treatment approach does not elevate NAD+ beyond natural levels, which is known to promote cancer, addressing a potential safety concern.

A New Direction in Alzheimer's Research

This study represents a significant departure from the dominant amyloid hypothesis that has guided Alzheimer's research for decades. While approved medicines targeting amyloid protein, such as Eli Lilly's Kisunla (donanemab) and Biogen and Eisai's Leqembi (lecanemab), have shown promise, they have been associated with rare but serious brain bleeding side effects and are unable to restore lost cognitive function.

Dr. Pieper emphasized the potential impact of this new approach, stating, "The key takeaway is a message of hope—the effects of Alzheimer's disease may not be inevitably permanent. The damaged brain can, under some conditions, repair itself and regain function."

Next Steps and Commercialization

Dr. Pieper is now working to advance P7C3-A20 through Glengary Brain Health, a Cleveland-based company he cofounded. The team had previously found that this investigational molecule could restore cognition in mice with long-term traumatic brain injuries, suggesting broader applications for the compound.

As research progresses, the pharmaceutical industry will be watching closely to see if this promising approach can be translated into effective treatments for human patients, potentially revolutionizing the landscape of Alzheimer's therapeutics.