Integrated genomic meta-analysis identifies cell-type-specific signatures and targets in early Alzheimer's disease

The preprint keeps APP in the frame for early Alzheimer's disease, but it does so through a neuro-glial signalling interaction, APP-CD74, rather than through amyloid load. That distinction matters against the one APP entry in the Claidex graph. Valiltramiprosate, an oral amyloid oligomer inhibitor tested in APOE4 homozygotes, failed its Phase 3 efficacy endpoint (valiltramiprosate-alz801-app-apoe4-alzheimers-phase3-efficacy-failure), which is the archetype that raises severity here even at a failure count of one. The useful reading is that a prioritisation exercise naming APP does not inherit the amyloid hypothesis, and any programme citing this work should say which APP-linked mechanism it is pursuing and how that mechanism differs from the one that has already read out negative in a powered trial. The repurposing candidates nominated here rest on pharmacological database integration rather than on clinical evidence, and carry no efficacy claim.