Differential and synergistic transcriptional effects of early amyloid-ß and tau pathologies in the hippocampus of APP, Tau, and APP/Tau female mice

Alzheimer's disease (AD) is characterized by memory loss associated with accumulation of amyloid-ß (Aß) and tau in the brain, but how memory-processing neural circuits are differentially affected by each pathology remains unclear. Here, we investigated the transcriptional vulnerability to single and concomitant Aß and tau pathologies in 6-month-old transgenic mice expressing mutant human amyloid precursor protein (APP), Tau, or both (APP/Tau mice) in excitatory neurons. We identified differential and synergistic pathology-induced transcriptional responses in the hippocampus of AD transgenic mice. These findings support the idea that Aß and tau pathologies exert synergistic effects to disrupt gene expression programs underlying vulnerability of memory neural circuits in AD. Overall design: To study the effect of single and concomitant early amyloid-ß (Aß) and tau neuropathologies on memory-processing circuits, 6-month-old APP, Tau, and double transgenic APP/Tau female mice were trained in the Morris water maze (MWM), and the bulk hippocampal transcriptomes were analyzed.