MAPT and Alzheimer disease: In AD, the pre-clinical stage is associated with build-up of the typical pathological AD “triad” signature; initially soluble amyloid beta (Aβ) species and interstitial cerebral “amyloid plaques” (A), the phosphorylation and subsequent aggregation of Tau proteins into neurofilament tangles within neurons (T), with progressive loss of cerebral volume and brain atrophy and other features of neurodegeneration (N) (10, 13, 14).