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). The gene discussed is INS; the disease is early-onset autosomal dominant Alzheimer disease.