NAD+ depletion is a hallmark of neuronal aging and Alzheimer's disease, impairing SIRT1/SIRT3-mediated neuroprotection. NMN (nicotinamide mononucleotide) supplementation can restore NAD+ but its CNS bioavailability and dose-response in neurons is unclear. The SLC12A8 transporter provides a potential route for direct NMN uptake. This challenge requires demonstrating that NMN reaches sufficient CNS concentrations and rescues metabolic function. Falsifiable prediction: oral NMN at 500mg/kg/day should restore cortical NAD+ by ≥50% vs aged controls and reduce p21 expression by ≥30% in cortical neurons of 18-month-old 3xTg-AD mice.