Unveiling FAD3T: A Groundbreaking Transgenic Mouse Model for Accelerating Alzheimer's Disease Research

Alzheimer’s disease (AD) research is often limited by long experimental timelines and models that fail to capture the full spectrum of human pathology. Here we present FAD3T, a next-generation transgenic mouse model on the C57BL/6J background carrying humanized APP, PSEN1, and MAPT genes with familial AD mutations.
FAD3T mice display translational plasma biomarkers as early as 1 month, including Aβ40, Aβ42, p-tau181, p-tau217, and neurofilament light chain (NfL). The model recapitulates a progressive amyloid cascade, followed by phosphorylated tau pathology and neuroinflammation by 6 months. These pathological changes translate into early spatial memory deficits, emerging at 3 months in females and 4 months in males, reflecting clinically relevant sex differences.
Overall, FAD3T integrates early biomarker translatability, progressive AD pathology, and sex-specific phenotypes, providing a powerful platform to accelerate Alzheimer’s disease research and therapeutic development.