1. Loss of PITRM1 function leads to AD-like pathological features. 2. PITRM1 deficient neurons show significantly low mitochondrial membrane potential and activates unfolded protein response.3. Reduced neuronal loss, Aβ42/Aβ40 ratio, tau hyperphosphorylation, and mitochondrial clearance is improved via nicotinamide mononucleotide mitophagy stimulation. Here, MAPT is linked to Alzheimer disease.