Maintained memory and long-term potentiation in a mouse model of Alzheimer's disease with both amyloid pathology and human tau

One of the key knowledge gaps in the field of Alzheimer's disease research is the lack of understanding of how amyloid beta and tau cooperate to cause neurodegeneration. We recently generated a mouse model (APP/PS1 + Tau) that develops amyloid plaque pathology and expresses human tau in the absence of endogenous murine tau. These mice exhibit an age-related behavioural hyperactivity phenotype and transcriptional deficits which are ameliorated by tau transgene suppression. We hypothesized that these mice would also display memory and hippocampal synaptic plasticity deficits as has been reported for many plaque bearing mouse models which express endogenous mouse tau. We observed that our APP/PS1 + Tau model does not exhibit novel object memory or robust long-term potentiation deficits with age, whereas the parent APP/PS1 line with mouse tau did develop the expected deficits. These data are important as they highlight potential functional differences between mouse and human tau and the need to use multiple models to fully understand Alzheimer's disease pathogenesis and develop effective therapeutic strategies.

Automated summary

The lack of understanding on how amyloid beta and tau cooperate to cause neurodegeneration is a key knowledge gap in Alzheimer's disease research. A mouse model (APP/PS1 + Tau) developed with amyloid plaque pathology and human tau expression without endogenous murine tau shows differences in behavioral hyperactivity phenotype and transcriptional deficits from mice with endogenous tau. The data highlight potential functional differences between mouse and human tau, emphasizing the need to use multiple models to fully understand Alzheimer's disease pathogenesis and develop effective therapeutic strategies.