THBS4 and Alzheimer disease: Among the first set of genes (i.e. those involved in AD relevant functions), we focused on Irs2, Nnt, Aldh1a1, Klf4, Egfl6, Hddc3, Stbd1, and Thbs4. Irs2 encodes insulin receptor substrate 2, a mediator of the insulin signaling pathway, which is compromised in AD [65].