Figure 3.

CK–p25 and CK–p25/PD-APP Tg mice accumulate Aβ in swollen axons in the white matter tract of the dorsal hippocampal commissure. a, 4G8 immunoreactivity was observed in swollen axons in CK–p25 mice (second panel) and to a greater extent in PD-APP/CK–p25 mice (fourth panel) induced for 8 weeks but not in WT (first panel) and PD-APP (third panel) control mice. b, Swollen axons were clearly visible by Bielchowsky silver stain, showing various degrees of impregnation from orange to black (second panel) and by hematoxylin and eosin staining, appearing as well defined, eosinophilic structures (fourth panel) in CK–p25 mice. Swollen axons were not detected in age-matched WT (first and third panels) or PD-APP (data not shown) controls. c, Electron microscopy of the swollen axons, shown in cross section (left panel) and longitudinal sections (right panel), revealed an amassment of organelles and vesicles and deteriorating myelination. Electron micrographs are from CK–p25 mice induced for 9 weeks. d, 4G8 immunoelectron micrographs revealed immunoreactive clusters in electron-dense, vesicular structures within swollen axons in CK–p25/PD-APP mice induced for 12 weeks. Aggregations are indicated by arrows. Inset is a magnification of area outlined by the smaller box. Scale bars, 200 nm.