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Author Spotlight: Enhancements in Gene Expression Regulation Research
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Author Spotlight: Enhancements in Gene Expression Regulation Research

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Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain

Guillermo Carbajosa1, Karim Malki2, Nathan Lawless2

  • 1Department of Biostatistics and Health Informatics, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.

Neurobiology of Aging
|June 16, 2018
PubMed

Insights

Loss of the TREM2 gene increases Alzheimer's disease risk. This study found Trem2 loss impacts brain endothelial cells and neuronal networks, suggesting a link between immune response and vascular dementia.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Rare heterozygous variants in the TREM2 gene are linked to increased risk of late-onset Alzheimer's disease.
  • The precise role of TREM2 in Alzheimer's pathogenesis remains incompletely understood.

Purpose of the Study:

  • To investigate the transcriptional consequences of Trem2 loss in the mouse brain.
  • To elucidate the role of TREM2 in brain cell homeostasis and its potential involvement in dementia.

Main Methods:

  • Differential gene expression and coexpression network analysis of RNA-Seq data from Trem2 knockout and wild-type mice at 4 and 8 months.
  • Analysis of cortex and hippocampus tissues.
  • Cell-type marker identification and gene ontology enrichment.

Main Results:

  • Trem2 loss led to significant transcriptional changes in the mouse brain.
  • An endothelial gene-enriched subnetwork showed altered activity at 4 months, with increased centrality of the amyloid precursor protein gene.
  • Disruption was observed in other cell-type subnetworks, including those with neuronal identity.

Conclusions:

  • TREM2 plays a role in endothelial cell homeostasis, extending beyond its known microglial functions.
  • These findings suggest a potential link between immune response and vascular disease in the context of dementia.
  • TREM2's multifaceted role may contribute to Alzheimer's disease pathogenesis through both immune and vascular mechanisms.
Keywords:
Alzheimer's diseaseEndothelial cellsKnockout mouse modelRNA-SeqTREM2Weighted gene coexpression network analysis

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