Figure 5.

Experimentally induced lysosomal dysfunction causes greater tau breakdown in hippocampal slices from apoE^−/− mice. Hippocampal slices cultured from wild-type (apoE^+/+) and apoE^−/− mice were incubated with vehicle (Con) or ZPAD for 6 days. Slices then were homogenized and processed for electrophoresis. Western blots were stained by using anti-nonphosphorylated tau-1 mAb. Note that ZPAD treatment induced a marked decrease in native tau (p50–55) (*, P < 0.001, two-tailed t test, in both apoE^+/+ and apoE^−/− slices) and an increase in the breakdown fragments at p29 kDa. Densitometric analysis (Lower) shows that ZPAD-induced breakdown of tau-1 is significantly greater (#, P < 0.001, t test) in apoE^−/− vs. apoE^+/+ hippocampal tissues.