Forebrain hShh overexpression mitigated the trisomy-caused early-onset severe cognitive impairment in Ts65Dn (P < 0.0001 for Eu;TRE-hShh VS Ts65Dn;TRE-hShh, and P = 0.14 for Eu; TRE-hShh VS Ts65Dn;Camk2a-hShh, Fig. 7C). This evidence concerns the gene CAMK2A and Cognitive impairment.