Supplemental Data

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Enhanced Neurofibrillary Degeneration in Transgenic Mice Expressing Mutant Tau and APP
Jada Lewis, Dennis W. Dickson, Wen-Lang Lin, Louise Chisholm, Anthony Corral, Graham Jones, Shu-Hui Yen, Naruhiko Sahara, Lisa Skipper, Debra Yager, Chris Eckman, John Hardy, Mike Hutton, and Eileen McGowan

Supplementary Material

Supplemental Figure 1. Comparison of tau expression in TAPP and JNPL3 (tau) transgenic mice. Two- month TAPP and JNPL3 mice were used for northern and western analysis. (A) Northern hybridization with a tau exon 11 oligonucleotide probe indicated equivalent amounts of mouse tau and human transgenic tau in TAPP and JNPL3 mice. Equal loading was determined by subsequent hybridization with a histone cDNA probe. (B) Western analysis of soluble tau demonstrated equivalent levels of transgenic human tau (E1 antibody) and total tau (WKS45 antibody) in the TAPP versus JNPL3 transgenic mice. Equal loading is shown by subsequent staining with an antibody to beta-tubulin. Although JNPL3 and TAPP mice have equivalent levels of transgenic and endogenous mouse tau, the TAPP mice have increased sarkosyle-insoluble (pathologic) tau at older ages in the cortex, amygdala and hippocampus compared to JNPL3 (tau) mice. This reflects the enhanced neurofibrillary pathology in the TAPP mice (see Fig. 3, main text).

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Supplemental Figure 2. Amyloid plaques in TAPP mice, aged 10-15 months, contain Abeta40 (A) and Abeta42 peptides (B) as demonstrated with carboxyl-terminal specific polyclonal antibodies. Neuritic elements in plaques contain phospho-tau epitopes as demonstrated by several different double staining methods, including thioflavin-S fluorescence coupled with tau immunoperoxidase staining (C and D). Note that adjacent to the amyloid core (*) are several tau (CP13) immunoreactive dystrophic neurites (arrows in C and D). Phospho-tau (PG5) immunoreactive neurites (arrows) and neurons are illustrated adjacent to amyloid deposits using double immunostaining with two different chromogens (PG5 with alkaline phosphatase - blue - and Abeta42 with peroxidase- brown) (E). Immunostaining for APP (22C11) demonstrates APP-immunoreactive dystrophic neurites (arrows) around plaque cores (F). Immunostaining with Ab39, a tangle-specific monoclonal antibody, shows positive immunoreactivity in NFT (H), but no immunostaining of dystrophic neurites in plaques (*) (G).

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