Scientists at UCSF and Gladstone Institutes used computational approaches to identify a combination of two FDA-approved anticancer drugs, letrozole and irinotecan, which reversed Alzheimer’s disease–related gene expression changes in brain cell types. Analysis of electronic health records revealed decreased Alzheimer's incidence among patients using these drugs for other indications. In mouse models, the combination reduced neurodegeneration and restored memory function, offering a promising therapeutic avenue for this neurodegenerative disease affecting 50 million people globally.