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

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. Her...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in genetics 2019-02, Vol.10, p.35-35
Main Authors: Neuner, Sarah M, Heuer, Sarah E, Zhang, Ji-Gang, Philip, Vivek M, Kaczorowski, Catherine C
Format: Article
Language:English
Subjects:
Alzheimer’s
Genetics
network analysis
resilience
susceptibility
transcriptomics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 , , and , 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.
ISSN:1664-8021
1664-8021
DOI:10.3389/fgene.2019.00035