Findings such as these, together with the prominence of Aβ plaques in Alzheimer neuropathology, led to development of the Amyloid Hypothesis [68], which has served in many ways to expand our understanding of how APP expression could be related to the development not only the Aβ plaque but to a range of the neuropathological features of AD, including neurofibrillary tangles, glial activation, and overexpression of neuroinflammatory cytokines. Here, APP is linked to Alzheimer disease.