APP and amyloidosis: Consequently, the direct link between APP, APP processing and AD formed the basis of the widely accepted amyloid cascade hypothesis which postulates that a protracted asymptomatic disease phase with well-defined spatiotemporal accumulations of pathological Aβ plaques in the temporal lobe, frontal lobe and limbic system precedes widespread neocortical and limbic NFTs, symptom onset, cognitive decline and dementia [34].