In the present study, we explored the interaction between APOE, astrocytes and protein aggregation focusing on non-demented individuals, including Aβ-negative cognitively unimpaired individuals, Aβ-positive cognitively unimpaired individuals (preclinical Alzheimer’s disease) and Aβ-positive patients with mild cognitive impairment (MCI) (prodromal Alzheimer’s disease). This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.