12/27/2025
For decades, Alzheimerās disease has been treated as an irreversible condition, with research aimed at slowing decline rather than restoring lost function. A December 2025 study published in Cell Reports Medicine directly challenged this assumption by testing whether brains with advanced Alzheimerās-like damage could recover. Researchers analyzed human Alzheimerās brain tissue alongside two well-established mouse models driven by different genetic causes ā one dominated by amyloid pathology and the other by tau pathology. Across both human and animal samples, they identified a pronounced breakdown in NADāŗ balance, a molecule essential for cellular energy, DNA repair, and neuronal survival. This deficit was far more severe than what is seen in normal aging, positioning disrupted brain energy metabolism as a central driver of disease progression rather than a secondary consequence.
To test whether this energy failure was reversible, the team restored NADāŗ balance using a targeted pharmacological compound (P7C3-A20) after significant disease had already developed. The results were striking: mice with advanced Alzheimerās-like pathology showed repair of synaptic function, reduced neuroinflammation, stabilization of the bloodābrain barrier, and full recovery of learning and memory performance. Importantly, blood levels of phosphorylated tau-217 ā a clinically used Alzheimerās biomarker in humans ā normalized, providing biochemical evidence that disease processes were reversed, not merely bypassed. While these findings apply only to animal models and require human clinical trials, they demonstrate that under specific conditions, the damaged brain may retain an unexpected capacity for structural and functional recovery through restoration of energy balance, reframing how Alzheimerās disease could be approached therapeutically in the future.