The relevance of these data regarding the conflictual reports about the levels of TGFβ in AD, is that in AD a substantial amount of the Smad complex does not reach the nucleus despite high serum and spinal fluid levels of TGF-β; therefore those high levels have fewer downstream consequences, i.e., functional effect, than if the entire Smad complex had entered the nucleus. The gene discussed is TGFB1; the disease is Alzheimer disease.