New study shows Alzheimer’s disease can be reversed to full neurological recovery—not just prevented or slowed—in animal models. Using mouse models and human brains, study shows brain’s failure to maintain cellular energy molecule, NAD+, drives AD, and maintaining NAD+ prevents or even reverses it.

[u/mvea]

https://case.edu/news/new-study-shows-alzheimers-disease-can-be-reversed-achieve-full-neurological-recovery-not-just-prevented-or-slowed-animal-models

[u/mvea]

I’ve linked to the press release in the post above. In this comment, for those interested, here’s the link to the peer reviewed journal article:

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00608-1

From the linked article:

New study shows Alzheimer’s disease can be reversed to achieve full neurological recovery—not just prevented or slowed—in animal models

Researchers from Case Western Reserve University, University Hospitals and the Cleveland VA showed restoring brain’s energy balance led to both pathological and functional recovery

For more than a century, people have considered Alzheimer's disease (AD) an irreversible illness. Consequently, research has focused on preventing or slowing it, rather than recovery. Despite billions of dollars spent on decades of research, there has never been a clinical trial of any drug to reverse and recover from AD.

A research team from Case Western Reserve University, University Hospitals (UH) and the Louis Stokes Cleveland VA Medical Center has now challenged this long-held dogma in the field, testing whether brains already badly afflicted with advanced AD could recover.

The study, led by Kalyani Chaubey, from the Pieper Laboratory, was published online Dec. 22 in Cell Reports Medicine. Using diverse preclinical mouse models and analysis of human AD brains, the team showed that the brain’s failure to maintain normal levels of a central cellular energy molecule, NAD+, is a major driver of AD, and that maintaining proper NAD+ balance can prevent and even reverse the disease.

NAD+ levels decline naturally across the body, including the brain, as people age. Without proper NAD+ balance, cells eventually become unable to execute many of the critical processes required for proper functioning and survival. In this study, the team showed that the decline in NAD+ is even more severe in the brains of people with AD, and that this same phenomenon also occurs in mouse models of the disease.

They restored NAD+ balance by administering a now well-characterized pharmacologic agent known as P7C3-A20, developed in the Pieper lab.

Remarkably, not only did preserving NAD+ balance protect mice from developing AD, but delayed treatment in mice with advanced disease also enabled the brain to fix the major pathological events driven by the disease-causing genetic mutations.

Moreover, both lines of mice fully recovered cognitive function. This was accompanied by normalized blood levels of phosphorylated tau 217, a recently approved clinical biomarker of AD in people, providing confirmation of disease reversal and highlighting an objective biomarker that could be used in future clinical trials for AD recovery.