Similarly, the level of STAT3 with the phosphorylated 705th tyrosine, an active form of STAT3, which was increased by the humanin/CLSP-mediated protective signaling, was reduced in the hippocampal neurons of AD patients and AD model mice18 SH3BP5 is the essential effector of the CLSP-mediated protective activity. This evidence concerns the gene CALML5 and Alzheimer disease.