Aged-dependent increase of the hippocampal axonal pathology in PS1/APP mice. A) APP-immunolabeled CA1 sections with Congo red at 6 (left) and 18 (right) months of age showing the age-dependent increase in the dystrophic neurite pathology. Dystrophies were concentrated surrounding Abeta plaques (insets in a1 and a2 show higher magnifications). The quantitative analysis of plaque-associated dystrophies demonstrated a significant increase in aged mice. B) Representative western blots (n=5/age/group) for phosphorylated (upper panel) and non-phosphorylated (lower panel) neurofilament (SMI antibodies). Bands corresponding to high (H) and medium (M) chains were indicated. Quantitative analysis revealed an increase in the phosphorylated vs non-phosphorylated H and M neurofilaments in aged PS1/APP mice. No changes were observed in 6 month-old PS1/APP or WT mice. C) Tau phosphorylation was determined by western blots using AT8 (upper panel), AT100 (medium panel) and tau (lower panel) antibodies at 6 and 18 months of age (n=5/age/group). Graph showed the quantitative analysis of AT8 western blots. Due to the lack of immunoreactivity in WT and 6 months PS1/APP mice, the AT100 signal could not be quantified. A prominent increase in AT100 epitope (absent in other conditions) was observed in 18 month-old transgenic mice. D) AT8 immunostaining revealed that phospho-tau concentrated principally in dystrophies around congophilic plaques. E) Western blots and quantitative analysis (n=5/age/group) of kinesin (upper panel) and dynein (lower panel) expression. Both motor proteins decreased in PS1/APP mice. So, stratum oriens; sp, stratum pyramidale; sr, stratum radiatum. Scale bars: 200 μm (a1/a2), 10 μm (inset a1), 20 μm (inset a2), 20 μm (D).