Recognition of the spread of Aβ deposits (from the entorhinal cortex to all hippocampal subregions and cortical areas) as an AD sign, and that AD progression is sustained by the self-propagation of Aβ oligomers, was based on both clinical observations of AD pathology (in humans and animal models), and on intracerebral inoculation of AD brain extracts (in nonhuman primates and human APP-expressing transgenic mice) resulting in accelerated Aβ deposition [43,44,45,46,47,48,49]. This evidence concerns the gene APP and Alzheimer disease.