Alzheimer’s disease affects millions of lives directly and indirectly every single day. Due to its profound global impact, substantial investment from governments, charities, and industry continues to support research aimed at understanding, preventing, and treating what has long been considered irreversible neurodegeneration. However, research published in 2025 has suggested that it may be possible not only to halt disease progression, but also to partially reverse existing damage, restoring cognitive function and memory. These findings challenge the long-held assumption that Alzheimer’s degeneration is irreparable and pave the way for a new wave of research focused on restoring neuronal function rather than simply slowing decline.
The study in question, conducted by Chaubey et al., employed aggressive mouse models of Alzheimer’s disease; the amyloid-driven 5xFAD model and the tau-driven PS19 model. When administered prophylactically, treatment with the small-molecule compound P7C3-A20 was shown to prevent the onset of disease in 5xFAD mice. In subsequent experiments, daily treatment was initiated at six months of age, a time point at which cognitive impairment and pathological deficits were already established.
Figure 1. Schematic overview of PI3C3-A20-mediated disease reversal in Alzheimer’s disease, highlighting changes in NAD⁺ homeostasis and proteomic profiles across AD mouse brains, recovered mouse brains, and human AD brains to identify potential mechanisms and therapeutic targets for AD reversal.p>.
Remarkably, intervention at this later stage induced widespread improvements in brain pathology. Treated animals exhibited reduced tau phosphorylation, suppression of neuroinflammation, and enhanced synaptic plasticity, among several other beneficial effects. Behavioural tasks were also used to assess cognitive performance, revealing full recovery of learning and memory functions compared with pre-treatment assessments.
Most notably, protein expression changes observed in the brains of humans with Alzheimer’s disease were mapped and identified within the mouse models. These disease-associated molecular signatures were found to be normalized following treatment with P7C3-A20, highlighting conserved pathological pathways and pinpointing potential therapeutic targets for future clinical translation.
These effects are thought to arise from the restoration of nicotinamide adenine dinucleotide (NAD⁺) homeostasis. The study demonstrated that this essential metabolic cofactor is severely depleted in Alzheimer’s-affected brains, with NAD⁺ levels correlating closely with disease severity. Treatment with P7C3-A20 not only increased brain NAD⁺ levels, but crucially restored physiological regulation, preventing levels from being driven excessively high.
Maintaining NAD⁺ homeostasis is fundamental to neuronal health, supporting energy metabolism, mitochondrial function, and cellular stress responses. In the context of Alzheimer’s disease, where ongoing cellular damage imposes a high metabolic burden, restoring NAD⁺ balance helps reduce secondary damage caused by metabolic strain and oxidative stress, thereby influencing multiple downstream pathological mechanisms. Rather than acting solely by reducing toxic protein accumulations, this approach improves outcomes by enhancing cellular resilience and resistance to degeneration.
These findings have profound implications for the future direction of neurodegeneration research. Alzheimer’s disease has long been characterised by the assumption that neuronal damage is irreversible. This study however provides compelling evidence that functional restoration may be achievable. As a result, targeting metabolic pathways that support neuronal resilience may now take precedence over, or be pursued in combination with, traditional amyloid and tau focused research. Importantly, this work also shifts attention toward translational questions, including whether the metabolic vulnerabilities and regulatory mechanisms which exist in the brain of a human with Alzheimer’s, can be therapeutically targeted with comparable efficacy.
Further work is undoubtedly required before we see NAD+ focused strategies implemented in a clinical setting. However, this study opens the door to a new generation of experimental approaches and disease models which are aimed not only at slowing neurodegeneration, but at repairing it. In doing so, it marks a meaningful shift in ambition for the field, from managing decline to restoring neuronal function.
Abbexa is committed to supporting research like this by providing scientists with reliable tools that enable accurate and reproducible results.
| ELISA kits | Antibodies | Proteins |
| Human Amyloid beta 40 (Abeta40) ELISA Kit abx053393 | Amyloid Oligomers (A11) Antibody abx448481 | Amyloid Beta 1-42 Protein abx060277 |
| Human Amyloid beta 42 (Abeta42) ELISA Kit abx053399 | Amyloid beta (N-Term) Antibody abx020623 | Human Amyloid Beta Peptide 1-42 (AB1-42) Peptide abx660044 |
Chaubey, K., Vázquez-Rosa, E., Tripathi, S. J., Shin, M. K., Yu, Y., Dhar, M., Chakraborty, S., Yamakawa, M., Wang, X., Sridharan, P. S., Miller, E., Bud, Z., Corella, S. G., Barker, S., Caradonna, S. G., Koh, Y., Franke, K., Cintrón-Pérez, C. J., Rose, S., Fang, H., … Pieper, A. A. (2026). Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain. Cell reports. Medicine, 7(1), 102535. https://doi.org/10.1016/j.xcrm.2025.102535
