Neuronal expression of E2F4DN modulates the immune response observed in the brain of 5xFAD mice.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder in which altered immune response is an important etiological factor. The transcription factor E2F4 participates in tissue homeostasis and regulates gene networks affected in AD, thus constituting a potential target for intervention. We have studied whether neuronal expression of a dominant negative form of E2F4 (E2F4DN), unable to become phosphorylated in a Thr motif that controls its activity, can modulate the immune response observed in AD. To this aim, we generated Mapt:E2F4DN knock-in mice (E2F4DN mice) that, together with control Mapt:EGFP knock-in mice (EGFP mice), were crossed with 5xFAD mice, a known murine model of AD. Our results are consistent with a beneficial immune response in 5xFAD mice expressing neuronal E2F4DN, which we propose as a therapeutic agent against AD.