In this study, we apply a systematic approach to detect, prioritize, validate and replicate GVU transcriptional perturbations in postmortem AD brains, test the top perturbed vascular transcript, SMAD3, for its associations with AD-related antemortem outcomes, perform in vitro validations of SMAD3 interactions with its predicted astrocytic molecular partner VEGFA in iPSC-derived pericytes and conduct in vivo experimental validations of SMAD3-VEGFA interactions and their consequences on BBB integrity in a well-established zebrafish model26–28. This evidence concerns the gene SMAD3 and Alzheimer disease.