Aβ42 and APOE-ε4 may exert their influence early, prior to the onset of neurodegeneration, consistent with work showing Aβ42 deposition plateaus between late MCI and AD development (Jack et al., 2013) and Aβ42 status more closely associates with cognitive decline in earlier disease states (Landau et al., 2012). Here, APOE is linked to Alzheimer disease.