Mechanistic evidence candidates require systematic preclinical validation pipelines before clinical consideration, with development prioritization favoring compounds demonstrating (1) strong network evidence combined with favorable pharmaceutical properties, (2) established safety profiles from approved indications enabling rapid repurposing, (3) druggable targets with validated assay systems for target engagement confirmation, and (4) mechanistic rationale addressing core AD pathologies (amyloid, tau, neuroinflammation) rather than purely symptomatic mechanisms. The gene discussed is MAPT; the disease is Alzheimer disease.