Can Advanced Alzheimer’s Be Reversed? What a New Mouse Study Found

Adapted from Chaubey et al’s paper Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain (Cell Reports Medicine, 2026)

Category: Drugs and Treatments

Key characteristics: Possible reversibility of Alzheimer’s 

mainDownload

Read Here

Vocabulary:

NAD+: A molecule found in every cell that helps produce energy, repair damaged DNA, and keep cells healthy. As we age—and especially in Alzheimer’s disease—NAD⁺ levels decline, making it harder for brain cells to function and protect themselves.

ATP: Often called the cell’s “energy currency,” ATP provides the energy cells need to perform everyday tasks, such as sending nerve signals, repairing damage, and maintaining healthy brain function. NAD⁺ helps cells produce ATP.

Amyloid plaques: Sticky clumps of amyloid-beta proteins that build up between brain cells. These plaques are a hallmark of Alzheimer’s disease and are thought to interfere with communication between neurons and contribute to inflammation. (think: sticky gum between two sphere)

Tau Tangles: Twisted bundles of a protein called tau that form inside brain cells. Normally, tau helps support the internal structure of neurons, but in Alzheimer’s disease it becomes abnormal, forming tangles that disrupt cell function and eventually lead to cell death. (think: a tangled yarn ball) 

AD Progression: As brain cells become damaged and die, people may experience increasing memory loss, confusion, difficulty with daily activities, changes in behavior, and eventually loss of independence. Three levels of progression. 

Blood-Brain Barrier (BBB): A protective layer of tightly packed cells that acts like a security checkpoint between the bloodstream and the brain. In Alzheimer’s disease, this barrier can become damaged, allowing toxins and inflammatory molecules to leak into the brain and worsen disease progression.

TLDR Summary

The study was sparked by the possible existence of brain resilience. The scientists noticed that those who carried autosomal dominant AD mutations (genes that are not related to the sex of the person) didn’t develop symptoms until later on. There were a few cases where nondemented people with Alzheimer’s neuropathy (NDAN) have abundant amyloid plaques but still retain cognitive function (this contrasts AD as the decline in cognitive function has been thought to be caused by an excessive buildup of amyloid plaques), implying the possibility of the brain having an intrinsic ability to delay or counteract disease progression. 

The study’s main mechanism focuses on NAD+ and its role in energy creation. In short, without NAD+, ATP, the body’s energy currency, cannot be created. The scientists leveraged how severity of Alzheimer’s disease (AD) correlates with NAD+ homeostasis dysregulation. 

The proposed drug P7C3-A20 increases NAD+ levels to homeostasis without creating excess amounts which could cause cancer. Rather than destroy the amyloid plaques directly to minimize disease severity, the drug supports the brain’s natural ability to repair itself and offset AD progression. The scientists tested their drug on mice induced with AD. The treated mice regained memory and showed healthier brains over time. 

Why is this a breakthrough?

Most of the current treatments and medications target the amyloid plaques and tau proteins. P7C3-A20, instead, works on rebalancing the brain’s NAD+ levels and preserving homeostasis. The success of P7C3-A20 has undermined the long-thought belief that AD is irreversible. 

Analogy: 

Increasing white blood cells levels instead of constantly changing out bandaids when healing a wound

Methods and Mechanisms Studied 

The scientists tested out two different mouse models of AD (one with amyloid plaques and the other with tau tangles). The medication was given to the rats after they developed symptoms to study how P7C3-A20 will impact amyloid plaques and tau tangles (instead of studying prevention). They evaluated the rats through:

• Brain tests: Behavioral tests, brain imaging, and lab analyses, labeled newly formed brain cells 
• Memory/Learning: maze-based tasks, remembering familiar objects, learning new environment
• Brain Energy: measured levels of NAD_
• BBB: High-resolution microscopy and protein markers looked into if the barrier remains intact or leaky 

Results

The researchers found that restoring NAD⁺ homeostasis led to widespread improvements in brain health.

• The rat’s memory and learning improved (healthy mice and treated mice performed similarly on cognitive tests)
• Brain cells regained ability to maintain healthy energy balance (NAD+ levels) 
• P-tau 217 biomarker, which is directly linked to tau game, decreased 
• Blood-brain barrier became healthier 
• Inflammation and DNA damage decreased 

Limitations

As the study focused on rat models, the findings may not be the same in human models. There may also be negative side effects when treatment is used on humans. Human patients with AD have varying severity, symptoms, and experiences—AD is an extremely complex disease. The drug may not treat and benefit all patients. 

More studies will also be needed to evaluate the drug’s long-term safety and effectiveness before clinical use or approval for clinical trials. 

Future Implications

The success of the study has opened a new field of exploration for AD research. Leveraging the brain’s natural mechanisms may be more effective than just destroying plaque and tangle buildups. Future research may include human clinical trials, looking into P7C3-A20’s long-term side effects. If the drug is effective against AD, its potential in curing other neurodegenerative diseases is another avenue of exploration. Even if P7C3-A20 cannot be used in humans due to unforeseen side effects, it has laid the groundwork for brain-support based AD drug development.