The contribution of APP, tau and presenilin to cognitive phenotypes in PLB mouse lines

Kaja Plucinska, Barry Crouch, David John Koss, Gernot Riedel, Bettina Platt

Research output: Contribution to conferencePosterpeer-review


Background: Novel Alzheimer’s disease (AD) mouse models, termed PLB, were generated
via targeted knock-in to allow a direct comparisons between single, double and triple transgenic mice. Lines express human (h) APPSWE/LON, or hTauP301L/R406W (PLB2APP and PLB2Tau, respectively), hAPP/hPS1 (PLB2APP/PS1) or hAPP/hTau/hPS1 (PLB1Triple) controlled by the CamKIIα promoter.
Methods: Behavioural and molecular profiling was performed to characterize PLB lines at 6 and 12 months. Here, we present activity-related and spatial memory phenotypes. Activity was assessed over 7 days via a home cage video-based observation system (PhenoTyper). Spatial memory was determined in the water maze (WM, 1 day visible platform & 4 days spatial acquisition with 4 trials/day) followed by a probe trial. Immunocytochemistry was employed to compare regional expression of APP/Aβ and/or tau in 12-month old PLB brain tissue, using anti-human 6E10 and HT7 antibodies.
Results: Circadian rhythms were preserved in all PLB lines, but drastic reductions in locomotion occurred during both light (range: -21% to -38%) and dark periods (-22% to -33%). Interestingly, at 6 months activity changes were somewhat graded, with single transgenics (PLB2APP and PLB2TAU) affected less cf. controls, while at 12 months PLB2APP/PS1 exhibited the least pronounced hypoactive profile than other transgenic groups. PLB1/2 mice were also impaired in spatial acquisition in the WM from 6 months, deficits were most prominent in aged PLB2APP/PS1 and PLB1Triple mice. Only PLB1Triple mice at 12 months of age were impaired during spatial memory recall. Additional analyses suggest that different learning strategies are employed across PLB mouse lines.
While sparse plaque load was observed in PLB2hAPP (with or without PS1), region- and genotype-specific patterns of intra- and extra-cellular APP/Aβ accumulation were detected. Similarly, mild yet consistent and region-specific expression of hTau occurred in both PLB2Tau and PLB1Triple forebrains. Tau pathology was overall strongest in PLB2Tau mice.
Conclusions: PLB1/2 mice exhibited normal general health, but all lines displayed disease-relevant activity and cognitive phenotypes with line-specific variations in severity, which emerged from 6 months onwards. In contrast to other AD models, PLB mouse lines offer analyses auf tau- vs. amyloid-related phenotypes and a convenient experimental window to investigate early cognitive impairments.
Original languageEnglish
Publication statusPublished - 16 Jul 2014
EventAlzheimer's Association International Conference - Copenhagen, Denmark
Duration: 19 Jul 201424 Jul 2014


ConferenceAlzheimer's Association International Conference


  • APP, tau, PS1


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