Our work provides evidence that mitochondria have an active role in the pathogenesis of AD, as reducing mitochondrial homeostasis via atf4 depletion in 5xFAD mice aggravates the hallmarks of the disease; conversely, boosting mitochondrial proteostasis by NMN decreases protein aggregation, restores memory performance, and delays disease progression, ultimately translating to increased healthspan. This evidence concerns the gene ATF4 and Alzheimer disease.