While prior studies report NAD+ depletion in Alzheimer’s disease (AD) models and partial attenuation of pathology with NAD+ precursor supplementation (1), the “more is better” approach has its limits. High doses of NAD+ precursors can produce supraphysiologic levels that may promote cancer, making them a risky long-term solution. In a recent study in Cell Reports Medicine (2), a team from Cleveland shows that the severity of Alzheimer’s disease correlates directly with the dysregulation of NAD+ homeostasis: it’s not just a lack of fuel, but a breakdown of the entire system. Instead of managing the brain by constantly dumping in new raw materials, they proposed that we simply need to add recycling trucks to the fleet.
By using the NAMPT activator P7C3-A20, Chaubey et al. (2) demonstrated that preserving brain NAD+ homeostasis prevents and even reverses AD in mice. The data behind this metabolic upgrade is compelling: by enhancing the NAD+ salvage pathway, treatment in advanced mouse models (5XFAD) successfully reversed cognitive deficits and stabilized blood-brain barrier integrity. The study highlighted a significant reduction in tau phosphorylation (specifically at the pTau-S396/S404 sites) and a 40% increase in hippocampal neurogenesis. By ensuring nicotinamide is constantly recycled back into functional NAD+, P7C3-A20 prevents the energetic exhaustion that triggers neuronal death without the risks of overloading the system.
At Medimabs, we might not be the ones driving the recycling trucks, but we provide the high-precision antibody tools you need to track exactly how these vital resources are being managed. Whether you require our isoform-specific tau antibodies (3, 4, 5, 6) or seek to develop custom antibody services tailored to your unique targets, our team is dedicated to helping your research hit the road toward the next breakthrough.