Quick Facts

• Mice with advanced Alzheimer’s achieved complete cognitive recovery after restoring brain NAD+ levels
• Human Alzheimer’s brains show 30% reduction in NAD+ levels compared to healthy brains
• Study challenges century-old assumption that Alzheimer’s damage is permanent and irreversible

A groundbreaking study published in Cell Reports Medicine has demonstrated that Alzheimer’s disease can be reversed in mice through restoring brain energy balance. The research challenges over a century of medical assumptions about the permanence of Alzheimer’s damage.

Researchers at University Hospitals found that mice with advanced Alzheimer’s-like disease achieved complete cognitive recovery after treatment restored levels of NAD+ (nicotinamide adenine dinucleotide), a compound essential for cellular energy production.

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

The study used two distinct mouse models carrying different human genetic mutations linked to Alzheimer’s. Both groups showed complete recovery of cognitive function after treatment, with blood tests showing normalized levels of phosphorylated tau 217, a clinical biomarker used to diagnose Alzheimer’s in humans.

Human brain tissue analysis revealed a 30% reduction in NAD+ levels in Alzheimer’s patients. The more severe the disease, the greater the disruption in NAD+ metabolism, mirroring observations in the mouse models.

The treatment approach differs significantly from current over-the-counter NAD+ supplements. The research used P7C3-A20, a compound that helps cells maintain proper NAD+ balance under stress without elevating levels to dangerous heights that could promote cancer.

For more than a century, Alzheimer’s has been viewed as permanent once it begins. Most research focuses on prevention or slowing progression rather than reversal. No drug trial has ever been designed with the goal of reversing Alzheimer’s and recovering cognitive abilities.

The research suggests that much of the cognitive decline in early and mid-stage Alzheimer’s may stem from dysfunctional cellular processes rather than irreversible neuron death. This represents a fundamental shift from the dominant amyloid hypothesis that has guided most treatment development.

Current FDA-approved Alzheimer’s drugs like Eli Lilly’s Kisunla and Biogen’s Leqembi can slow progression but cannot restore lost cognitive function. They also carry risks of serious brain bleeding side effects.

In the mouse studies, restoring NAD+ balance reversed hallmark features of Alzheimer’s including tau phosphorylation, brain inflammation, oxidative stress, blood-brain barrier damage, and impaired neurogenesis. Treated mice performed memory tasks as well as healthy controls.

An estimated 7.4 million Americans age 65 and older live with Alzheimer’s in 2026. Without medical breakthroughs, this number could reach 13.8 million by 2060. Health and long-term care costs are projected to reach $409 billion in 2026.

Read more: Can Alzheimer’s Be Reversed? New Research Points To A Surprising Pathway