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. 

While AD is a uniquely human condition, it can be studied in the laboratory with mice that have been genetically engineered to express genetic mutations known to cause AD in people.