Another problem with the models has been the general difficulty of inducing the characteristic cytoskeletal pathology of AD in transgenic mice.59 NFTs are recognized by their propensity to stain with histological dyes, such as thioflavin-S and Congo red, and by ultrastructurally containing paired helical filaments. NFTs contain hyperphosphorylated forms of tau as well as conformationally altered tau epitopes that can be recognized by specific antibodies. In PDAPP mice, phosphorylated tau epitopes do accumulate within dystrophic neurites in animals 14 months of age or older,60 and within these neurites, 12- to 15-nm filaments can be seen, but there are no paired helical filaments and no lesions with the histological staining properties of NFTs. Other models have been similar in their lack of any NFT-like pathology. Various suggestions have been advanced for the difficulty of inducing NFT-like lesions in the mouse, including differences between human and mouse tau and the shorter life span of the mouse. However, the reasons remain unexplained.
