Nishimoto and colleagues proposed that TGF-beta promotes neuronal cell death by binding to APP and activating APP-associated signaling, and suggested that this could be one of the mechanisms of neuronal loss in Alzheimer's disease, as both neuronal and glial expression of TGF-beta are upregulated in AD brains [41, 42]. Here, APP is linked to early-onset autosomal dominant Alzheimer disease.