AUTHOR=Neuner Sarah M. , Heuer Sarah E. , Zhang Ji-Gang , Philip Vivek M. , Kaczorowski Catherine C. 

TITLE=Identification of Pre-symptomatic Gene Signatures That Predict Resilience to Cognitive Decline in the Genetically Diverse AD-BXD Model

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00035

DOI=10.3389/fgene.2019.00035

ISSN=1664-8021

ABSTRACT=<p>Across the population, individuals exhibit a wide variation of susceptibility or resilience to developing Alzheimer’s disease (AD). Identifying specific factors that promote resilience would provide insight into disease mechanisms and nominate potential targets for therapeutic intervention. Here, we use transcriptome profiling to identify gene networks present in the pre-symptomatic AD mouse brain relating to neuroinflammation, brain vasculature, extracellular matrix organization, and synaptic signaling that predict cognitive performance at an advanced age. We highlight putative drivers of these observed relationships, including <italic>Itgb2</italic>, <italic>Fcgr2b, Slc6a14</italic>, and <italic>Gper1</italic>, which represent prime targets through which to promote resilience prior to overt symptom onset. In addition, we identify a genomic region on chromosome 2 containing variants that directly modulate resilience network expression. Overall, work here highlights new potential drivers of resilience to AD and contributes significantly to our understanding of early, potentially causal, disease mechanisms.</p>