Boosting NAD+ levels by NMN, NR, or mitotherapy enhance autophagy and mitophagy via SIRT1 signaling, by promoting clearance of Aβ, damaged mitochondria, and hallmark proteins, ameliorating behavioural and cognitive impairments in AD models; overexpression of SIRT1/SIRT5, PARP mutation/inhibition restores mitochondrial function and autophagy, slowing AD progression. This evidence concerns the gene SIRT5 and Alzheimer disease.