5XFAD mice display Caspase-3 activation in neurons with intraneuronal Aβ42. Parasagittal brain sections from 1.5 (A, E, C, G, K) and 4 month (B, D, F, H-J, L) 5XFAD (A-D, K, L), non-transgenic littermate (Non-Tg; E-H), and 5XFAD; BACE1−/− (I, J) mice were co-incubated with antibodies against activated Caspase-3 (green) and Aβ42 C-terminal neo-epitope (red) and imaged by confocal microscopy. Sections were co-stained with DAPI to detect nuclei (blue). Activated Caspase-3 is present in 5XFAD large pyramidal neurons of Layer 5 cortex (A, B, K, L) and subiculum (C, D) that also display intraneuronal Aβ42. At high magnification, activated Caspase-3 is distributed throughout in the soma and proximal dendrites of Aβ42-positive neurons (K, L). Neither activated Caspase-3 nor intraneuronal Aβ42 are present in neurons of Non-Tg (E-H) or 5XFAD; BACE1−/− (I, J) mice. Note presence of amyloid plaques (red) at 4 months in 5XFAD brain (B, D). Activated Caspase-3-positive ring-like structures (arrows, B, D) may represent neurons in the process of degeneration. Asterisk in A identifies background capillary staining. Scale bar A-J = 20 μm; K, L = 10 μm.