Alzheimer’s disease has been deemed irreversible since its identification over a hundred years ago. However, a groundbreaking study is challenging this long-standing belief as scientists have managed to reverse advanced stages of Alzheimer’s in mice. The researchers discovered that in human brains afflicted with Alzheimer’s, there is a failure to maintain normal levels of a cellular energy molecule known as NAD+. This deficiency is a significant contributor to the onset of Alzheimer’s.
By using mouse models, the scientists successfully restored the balance of NAD+ in the brain, even in instances of severe Alzheimer’s. This restoration enabled the brain to reverse the disease and regain cognitive function.
The treated mice also exhibited normalised blood levels of phosphorylated tau 217 – abnormal levels of which have recently been recognised as markers of Alzheimer’s disease in humans.
The authors of the study, published in Cell Reports Medicine, are optimistic that it could pave the way for potential recovery from Alzheimer’s in humans through therapies that re-establish the brain’s energy equilibrium. They also hope it will stimulate further research into complementary methods and clinical trials.
The research team comprised experts from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center, under the leadership of Kalyani Chaubey, PhD, from the Pieper Laboratory.
Andrew A. Pieper, MD, PhD, lead author of the research, stated: “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.”
Dr Chaubey added further context, saying: “Through our study, we demonstrated one drug-based way to accomplish this in animal models, and also identified candidate proteins in the human Alzheimer’s disease brain that may relate to the ability to reverse Alzheimer’s disease.”
NAD+ levels throughout the body naturally decline with age. The research team’s analysis revealed that in the brains of those living with Alzheimer’s disease, this decline is more pronounced and is also present in mouse models of the condition.
When NAD+ levels fall out of balance, cells ultimately lose their capacity to carry out the vital processes and proper functioning necessary for survival.
This research built upon the team’s earlier work, which demonstrated that restoring NAD+ balance in the brain could enable recovery following severe and prolonged traumatic brain injuries.
Regarding future plans following this breakthrough discovery, Dr Pieper stated: “This new therapeutic approach to recovery needs to be moved into carefully designed human clinical trials to determine whether the efficacy seen in animal models translates to human patients.
“Additional next steps for the laboratory research include pinpointing which aspects of brain energy balance are most important for recovery, identifying and evaluating complementary approaches to Alzheimer’s reversal, and investigating whether this recovery approach is also effective in other forms of chronic, age-related neurodegenerative disease.”