We have revealed an olfactory proteostasis impairment across neuropathological grading detecting: i) differential expression of 278 proteins between controls and AD phenotypes, ii) a progressive modulation of APP, and Tau interactome networks across AD stages, iii) alteration in MKK3-6/p38 MAPK, and PDK1/PKC signaling pathways, and iv) potential mitochondrial impairment due to the imbalance of Prohibitin (Phb) complex. This evidence concerns the gene PDK1 and Alzheimer disease.