The current study represents a systematic investigation on the anti-AD effects of DMT and its association with the modulation of neuronal Sig-1r-mediated ER-mitochondria signaling in the 3×TG-AD transgenic mouse model of AD and Aβ-exposed primary hippocampal neurons with additional utilization of Sig-1r knockdown mice and the Sig-1r antagonist BD1063. This evidence concerns the gene SIGMAR1 and Alzheimer disease.