The aim of the ASIC-E4 (“Beta-Amyloid, Synaptic loss, Inflammation and Cognition in healthy APOEε4 carriers”) study is to uncover the early interplay of three key pathological features of AD, i.e., synaptic dysfunction and loss, neuroinflammation and Aβ deposition, in cognitively normal individuals with either high, intermediate, or typical APOE-related genetic risk of late-onset AD. Here, APOE is linked to Alzheimer disease.