As such, over the years the field has pulled back from the idea that the amyloid cascade is the primary driver of late-onset AD, and either focused on alternative mechanistic pathways including tau, microglia, and additional genetic factors (such as apolipoprotein E, ApoE), or proposed alternative “dual pathway” or “probabilistic” models that focus less on pathological protein aggregation and more on common upstream drivers of disease [4,5,6,7,8]. Here, APOE is linked to Alzheimer disease.