IRS4 and early-onset autosomal dominant Alzheimer disease: In males, transcriptomic remodeling was characterized by strong enrichment in KEGG pathways related to “oxidative phosphorylation,” “circadian rhythm,” and neurodegenerative diseases, including “Alzheimer's disease.” Cana downregulated key genes of inflammatory and insulin‐related signaling (Socs1, Irs2, Irs4, Rps6ka4, Jund, Akt1s1, Map2k2, and Bace1), while upregulated genes were associated with metabolic regulation and neuroprotection (Irs1, Phkg1, Flot1, Casp9, Csnk2b, and Wnt11) (Figure 4B,C and Figure S2A).