Of the three major ApoE isoforms ApoE2, ApoE3 and ApoE4 [183], the E4 isoform is strongly associated with the onset of AD and disease progression, thus reducing the ApoE4 level is hypothesized to induce reduction of Aβ accumulation and attenuation of cognitive deficits. The gene discussed is APOE; the disease is Cognitive impairment.