IARS1 and Alzheimer disease: Several studies have reported that the early phase of AD might be associated with insulin receptor (IRs)/IGF-1R resistance, manifested as increased serum IGF-1 levels and reduced expression of IRs, IGF-1Rs, and their downstream substrates IRS-1 and IRS-2 in the brain, followed by decreased levels of serum IGF-1 at later stages of this amyloidosis (267–271).