INS and Alzheimer disease: Firstly, we demonstrated using KEGG signaling pathway clustering that age-related proteomic changes in the hypothalamus were potentially associated with neurodegenerative phenotypes (Alzheimer's disease, Parkinson's disease, Huntington's disease), cognitive and neurodevelopmental function (axon guidance, long-term potentiation, Notch signaling, Wnt signaling pathway), dysglycemia (Type II diabetes mellitus, insulin signaling), and neuronal cytoskeletal remodeling (Focal adhesion, Gap junction, Regulation of actin cytoskeleton) (Fig. 3).