BACKGROUND: Nuclear factor erythroid 2-related factor 2 (NRF2) regulates antioxidant defenses and protects against neurodegeneration, including Alzheimer's disease (AD). Its age-related decline disrupts redox balance and increases neuronal vulnerability, but the early hippocampal effects remain unclear. Here, we tested whether NRF2 loss affects tau seeding and spreading in a PHF-tau-inoculated mouse model, contributing to accelerated aging. METHODOLOGY: Three-month-old NRF2-knockout (Nfe2l2 RESU...