Time course of the natural development of cortical pathology in K3 and APP/PS1 mice. (A), (B), (C), (D), (E), (F) Micrographs of hyperphosphorylated tau labelling (red), using the AT8 antibody, in the neocortex (A to C) and hippocampus (D to F) of untreated K3 mice at 3 months (A, D), 6 months (B, E) and 12 months (C, F) of age. (G), (H), (I) Micrographs of amyloid-beta (Aβ) labelling (green), using the 6E10 antibody, in neocortex of untreated APP/PS1 mice at 3 months (G), 4.5 months (H) and 12 months (I) of age. Arrowheads indicate intraneuronal Aβ labelling, arrows indicate extracellular plaques. Comparable immunolabelling was achieved with the 4G8 antibody. Sections were co-labelled for glial fibrillary acidic protein (red), a marker of astrocytes. For all sections, nuclei were labelled with bisbenzimide (blue). Scale in (H) applies to (A) to (G).