In a landmark study, US scientists have demonstrated for the first time in animal models that Alzheimer’s disease can potentially be reversed, challenging over a century of beliefs that the neurodegenerative condition was irreversible.
The research, published in Cell Reports Medicine, used a combination of preclinical mouse models and analyses of human Alzheimer’s brains to reveal the critical role of NAD+, a central cellular energy molecule, in the progression of the disease.
The study found that NAD+ levels decline sharply in Alzheimer’s patients, a trend mirrored in mouse models.
By maintaining or restoring NAD+ balance, the researchers were able to both prevent the onset of Alzheimer’s and reverse advanced disease pathology in mice.
Senior author Andrew A Pieper, Director of the Brain Health Medicines Centre at the Harrington Discovery Institute, said, “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 strengthens the idea that restoring NAD+ might help patients recover from Alzheimer’s.”
The team studied mice carrying human mutations in amyloid processing and tau protein, key drivers of Alzheimer’s. They administered a pharmacological agent, P7C3-A20, to restore NAD+ levels.
Remarkably, mice treated before disease onset avoided Alzheimer’s entirely, while mice with advanced disease regained cognitive function after delayed treatment.
Both lines of mice exhibited complete recovery from the genetic and pathological hallmarks of the disease.
While the study remains preclinical, the findings offer promising new avenues for Alzheimer’s research and potential therapies.
Restoring NAD+ balance could emerge as a transformative strategy in combating one of the most challenging neurodegenerative diseases of our time.
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