Updated project metadata. The hippocampus is a primary region affected in Alzheimer’s disease (AD). Because AD postmortem brain tissue is not available prior to symptomatic stage, we lack understanding of early cellular pathogenic mechanisms. To address this issue, we examined the cellular origin and progression of AD pathogenesis in patient-based model systems including iPSC-derived brain cells transplanted into the mouse brain hippocampus, as well as human post-mortem hippocampal tissues. Our data showcase patient-based models to study the cellular origin, progression, and prion-like spread of AD pathogenesis.