IRS1 and Alzheimer disease: Insulin Receptor Substrate 2 (IRS2), which was upregulated in the thiamine deficient group, is a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines; IRS2 is predominant over IRS1 in the brain, and genetic ablation of IRS2 in mice reduces amyloid in an AD mouse model (Ochiai et al., 2021).