Using combined models of PGC-1α overexpression in the hippocampal dentate gyrus (DG) of AD-model mice and PGC-1α knockout mice, we investigated the effects of gain- and loss-of-function of PGC-1α on the regulation of the FNDC5/BDNF/TrkB signaling pathway, as well as on the survival of newborn neurons in the AD-affected hippocampus. This evidence concerns the gene FNDC5 and Alzheimer disease.