The ApoE4 variant of the ApoE gene is the major known risk factor for sporadic Alzheimer’s disease, as Elizabeth Mormino, PhD, of Stanford University, Stanford, CA, explains in this video, recorded at the Alzheimer’s Association International Conference (AAIC) 2018, held in Chicago, IL. ApoE4 is associated with unusual amyloid levels, and these two risk factors combine to increase the likelihood of rapid Alzheimer’s disease progression. Dr Mormino also explains how genetic screening for ApoE4 and imaging techniques can be combined, for example in patients with the ApoE4 variant but no amyloid deposition, to improve our understanding of disease mechanisms in Alzheimer’s and other neurodegenerative diseases. Finally, she discusses other mechanisms associated with ApoE4 that might lead to neurodegeneration.