The initial and key observation was that the addition of Aβ increased synaptic cholesterol concentrations, an observation that is consistent with reports of increased cholesterol concentrations in Aβ-positive synapses in the cortex of patients with AD.6 Surprisingly, this was not due to cholesterol synthesis, rather the Aβ-induced increase in synaptic cholesterol concentrations was controlled by the cholesterol ester cycle; it was accompanied by a corresponding reduction in cholesterol ester concentrations indicating the activation of a cholesterol ester hydrolase (CEH). The gene discussed is LIPA; the disease is Alzheimer disease.