Although the effect of a high-fat diet alone remains controversial [33,50], it deteriorates both systemic and central insulin resistance and worsens hippocampal insulin signaling and cognitive dysfunction in animals with Alzheimer’s disease-like symptoms such as injecting Aβ(25–35) or Aβ(1–40 or 1–42) into the brain [34,51,52]. This evidence concerns the gene INS and early-onset autosomal dominant Alzheimer disease.