NEW PUBLICATION: Lifestyle shapes preclinical social and microglial deficits in an Alzheimer’s disease mouse model.

Using our novel enrichment paradigm, we demonstrated early and progressive deficits in social parameters in the App knock-in mouse model of Alzheimer’s disease( AD), suggesting preclinical behavioral vulnerability. We found AD pathology impairs immune surveillance at a very early stage, with increased microglia coverage in more socially active animals. Single-cell RNA sequencing of hippocampal microglia revealed that enrichment dampened interferon-responsive microglia, which typically increase as amyloidosis advances. A shifted immune response was also measured by reduced transcripts related to antigen processing and presentation and by increased chemokine signaling. 

Our study demonstrates that the preclinical phase of AD is not silent, but even in a reductionistic knock-in model characterized by early interwoven preclinical changes in multiple domains, including brain plasticity, behavioral trajectories, sociality and immunity.