Researchers Reverse Advanced Alzheimer’s Symptoms in Mice
Scientists have demonstrated pharmacologic reversal of advanced Alzheimer’s disease in mice, restoring memory function through targeted restoration of a key cellular energy molecule. The treatment boosted levels of nicotinamide adenine dinucleotide, a coenzyme essential for cellular metabolism that declines sharply in Alzheimer’s brains. Mice modeling severe disease stages regained performance on memory tasks equivalent to healthy controls after receiving the compound. Human brain samples from Alzheimer’s patients showed similarly depleted NAD+ levels, suggesting a conserved mechanism across species.
The intervention used a precursor molecule that crosses the blood-brain barrier to replenish NAD+ stores. Treated mice exhibited reduced amyloid plaques and tau tangles, hallmarks of the disease, alongside normalized neuronal activity. Control groups without treatment continued to decline, confirming the compound’s specific effects. Researchers identified multiple therapeutic nodes in human postmortem brains where NAD+ restoration could intervene.
This approach addresses mitochondrial dysfunction central to Alzheimer’s progression. Declining NAD+ impairs energy production and DNA repair in neurons, accelerating cell death. Supplementation reversed these deficits in the mouse model, enabling synaptic repair and cognitive recovery even at late stages. The study mapped parallel pathways in human tissue for potential translation.
Findings appeared in Cell Reports Medicine, detailing dose-dependent improvements across behavioral, biochemical, and histological measures. Mice performed maze navigation and object recognition tests at pre-disease levels post-treatment. Untreated counterparts showed persistent deficits. The compound achieved brain concentrations sufficient to activate sirtuins and other NAD+-dependent enzymes.
This breakthrough challenges views of Alzheimer’s as inevitably progressive. Prior efforts focused on plaque removal yielded limited cognitive gains. NAD+ repletion targets upstream metabolic failure, offering broader neuroprotection. Researchers plan safety studies for human trials, noting the precursor’s existing use in other conditions.
The work highlights age-related NAD+ decline as a modifiable risk factor. Brain levels drop dramatically in Alzheimer’s compared to normal aging. Restoration not only halted progression but reversed established pathology in the model. Identification of conserved nodes supports applicability to human disease stages.
