4.1. Transgenic Mice

The generation of the Tg4–42 line was previously described [21]. In brief, the human Aβ_4-42 sequence is fused to the signal peptide sequence of the thyrotropin-releasing hormone and the expression is under the control of the Thy1 promoter. The Tg4–42 mice were bred to homozygosity (Tg4–42^hom). The line was generated and maintained on a C57BL/6J genetic background.

PS19 mice overexpress human tau with the P310S mutation under the control of the murine prion protein promoter [26] and were purchased from Jackson laboratories (Bar Harbor, ME, USA) (B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J). Mice were backcrossed to C57Bl/6J for more than 5 generations.

Bigenic mice (PS19/Tg4–42^hom) were generated by breeding transgene-positive Tg4–42^hom and PS19 mice and were maintained on a C57BL/6J genetic background. Accordingly, littermates were only obtained for Tg4-42^hom and PS19/Tg4-42^hom (with an additional tau transgene). In a second line of breeding, WT mice were bred with heterozygous PS19 mice to obtain WT and PS19 littermates. An equal number of female and male transgenic and age-matched C57Bl/6J (WT) mice at 3, 5 and 9 months of age were used in the present study. All animals were handled according to the German guidelines for animal care and all experiments have been approved by the local animal care and use committee (LAVES, Lower Saxony, Germany). Food and water were provided ad libitum.