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). Here, IRS2 is linked to Alzheimer disease.