NEW DELHI: In a significant breakthrough, US researchers have found in animal studies that Alzheimer's disease can be reverse, challenging previous studies that for over a century considered the neurodegenerative disease to be irreversible.
The new study, published in the journal Cell Reports Medicine and based on diverse preclinical mouse models and human Alzheimer's brains, demonstrated that maintaining proper NAD+ balance can prevent and even reverse the disease.
NAD+ is a central cellular energy molecule and a major driver of Alzheimer's.
The team also showed that the decline in NAD+ is even more severe in the brains of people with Alzheimer's, and that this also occurs in mouse models of the disease.
"We were very excited and encouraged by our results," said Andrew A. Pieper, senior author of the study and Director of the Brain Health Medicines Center, Harrington Discovery Institute at University Hospitals.
"Restoring the brain's energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer's. Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the idea that restoring the brain's NAD+ balance might help patients recover from Alzheimer's," he added.
The team studied mice engineered to express genetic mutations that cause Alzheimer's in people in the laboratory. The researchers used two of these models.
One line of mice carried multiple human mutations in amyloid processing, and the other mouse line carried a human mutation in the tau protein.
After finding that NAD+ levels in the brain declined precipitously in both human and mouse Alzheimer's, the research team tested whether preventing the loss of brain NAD+ balance before disease onset, or restoring brain NAD+ balance after significant disease progression, could prevent or reverse Alzheimer's, respectively.
They restored NAD+ balance by administering a now well-characterised pharmacological agent known as P7C3-A20.
Remarkably, not only did preserving NAD+ balance protect mice from developing Alzheimer's, but delayed treatment in mice with advanced disease also enabled the brain to fix the major pathological events caused by the genetic mutations. Moreover, both lines of mice fully recovered cognitive function.