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. 2001 Jul 3;98(15):8832–8837. doi: 10.1073/pnas.151253098

Figure 1.

Figure 1

Induction of tangle-like structures in cultured hippocampal slices prepared from apoE−/− mice. Slices from apoE−/− mice were incubated with vehicle (A) or ZPAD, an inhibitor of cathepsins B and L (B), for 6 days and then processed for immunocytochemistry using a mAb (AT8) that recognizes hyperphosphorylated tau proteins and neurofibrillary tangles in human tissue. Immunopositive elements are found in the outgrowth regions of the control slice from an apoE−/− mouse but not within the hippocampus itself. In contrast, the ZPAD-treated slice has numerous, densely labeled cells in stratum oriens of hippocampal field CA1 and in the subiculum. Note that the densely packed neurons in stratum pyramidale of field CA3 and in stratum granulosum of the dentate gyrus are not stained. (Lower) AT8 immunoreactivity in slices from wild-type mice treated with vehicle (C) or ZPAD (D) for 6 days. Note the lack of AT8-immunopositive cells in vehicle-treated slices and the small number of AT8-immunopositive cells in ZPAD-treated slices. (Bar = 200 μm.)