MAPT and early-onset autosomal dominant Alzheimer disease: In another study modeling peripheral insulin resistance in IRS2 knock out (KO) mice Schubert and colleagues show that neurofibrillary tangles composed of hyperphosphorylated tau aggregates accumulate in the hippocampus of IRS2 KO mice, revealing a direct molecular link between diabetes and Alzheimer's disease (Schubert et al., 2003).