The state of BIR, clinically defined as failure of insulin (delivered into the brain via the intranasal route to bypass the blood-brain barrier) to elicit a neuroimaging (FDG-PET or functional magnetic resonance imaging) or neurophysiological (e.g., electroencephalography) appears to be an early and common feature in human AD patients (Heni et al., 2015; Kullmann et al., 2016; Kellar and Craft, 2020). The gene discussed is INS; the disease is Alzheimer disease.