Moving away from amyloid Beta to move on in Alzheimer research

The ABC hypothesis was reinforced by the identification of gene defects in APP, PSEN1, and PSEN2 in patients with an early-onset, inherited form of the disease, and further strengthened when transgenic mouse models that express familial human APP and PSEN mutations recapitulate most features of human disease. [...]the role of glial cells in the ABC hypothesis is reduced to an Aβ elimination route and does not consider their recently recognized participation in all essential neurological tissue functions (Kettenmann et al., 2011; Oberheim et al., 2012). [...]if Aβ were as toxic as claimed, how can one explain cognitive health in subjects that contain Aβ accumulations that would credit Alzheimer disease? [...]the ABC hypothesis ignores typical characteristics of the disease, such as the spatiotemporal pattern of affected brain areas, the presence of white matter hyperintensities (Kandiah et al., 2015), and vacuolated cells (Nelson et al., 2012).