Soluble amyloid-β (Aβ) oligomers, a key driver of pathogenesis in Alzheimer disease, bind to cellular prion proteins (PrPC) expressed on synaptosomes resulting in increased cholesterol concentrations, movement of cytoplasmic phospholipase A2 (cPLA2) to lipid rafts and activation of cPLA2. This evidence concerns the gene PRNP and early-onset autosomal dominant Alzheimer disease.