Successful translation requires systematic validation pipelines, including (1) target engagement confirmation in neuronal cell models; (2) effects on AD-relevant pathologies (Aβ aggregation, tau phosphorylation, synaptic dysfunction) in human iPSC-derived neurons or brain organoids; (3) cognitive and pathological outcomes in transgenic AD mouse models (APP/PS1, 5xFAD, 3xTg-AD); and (4) biomarker-supported proof-of-concept clinical trials in prodromal or early AD populations. Here, APP is linked to Alzheimer disease.