The current study investigated whether IR and other markers associated with DM (plasma glucose, CSF and plasma insulin) may act as an early endophenotype of AD pathology by examining levels of the best validated molecular biomarkers of AD, CSF levels of amyloid β (Aβ), total tau (T-tau) and tau phosphorylated at the Thr181 epitope (P-tau), in cognitively healthy, age and APOE ε4 genotype-matched IR and non-IR subjects. This evidence concerns the gene APOE and Alzheimer disease.