ArticleNeurobiology of disease2017
Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury.
Article in Neurobiology of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Genetic variation in TMEM106B alters microglial activation and cytokine responses in chronic traumatic encephalopathy.Acta neuropathologica · 2025Article
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Deciphering microglial activation and neuronal apoptosis post‑traumatic brain injury: The role of TYROBP in inflammation regulation networks.Molecular medicine reports · 2024Article
- Large-scale gene expression changes in APP/PSEN1 and GFAP mutation models exhibit high congruence with Alzheimer's disease.PloS one · 2024Article
- Investigation of early molecular alterations in tauopathy with generative adversarial networks.Scientific reports · 2023Article
- Role and regulatory mechanism of microRNA mediated neuroinflammation in neuronal system diseases.Frontiers in immunology · 2023Review
- Review
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Identification of the hub genes and transcription factor-miRNA axes involved inOncology letters · 2022Article
- Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration.Frontiers in aging neuroscience · 2022Review
- Region-Specific Differences in the Apoe4-dependent Response to Focal Brain Injury.Experimental neurobiology · 2021Article
- The influence of ApoE4 on the clinical outcomes and pathophysiology of degenerative cervical myelopathy.JCI insight · 2021Article
- AXL kinase-mediated astrocytic phagocytosis modulates outcomes of traumatic brain injury.Journal of neuroinflammation · 2021Article
- High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice.Nature communications · 2021Article
- Early onset senescence and cognitive impairment in a murine model of repeated mTBI.Acta neuropathologica communications · 2021Article
- Transcriptional Pathology Evolves over Time in Rat Hippocampus after Lateral Fluid Percussion Traumatic Brain Injury.Neurotrauma reports · 2021Article
- A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome.Frontiers in aging neuroscience · 2021Review
- The Emergence of Model Systems to Investigate the Link Between Traumatic Brain Injury and Alzheimer's Disease.Frontiers in aging neuroscience · 2021Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) is strongly linked to an increased risk of developing dementia, including chronic traumatic encephalopathy and possibly Alzheimer's disease (AD). APOEε4 allele of human Apolipoprotein E (APOE) gene is the major genetic risk factor for late onset AD and has been associated with chronic traumatic encephalopathy and unfavorable outcome following TBI. To determine if there is an APOE isoform-specific response to TBI we performed controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4 isoforms. Following injury, we used several behavior paradigms to test for anxiety and learning and found that APOE3 and APOE4 targeted replacement mice demonstrate cognitive impairments following moderate TBI. Transcriptional profiling 14days following injury revealed a significant effect of TBI, which was similar in both genotypes. Significantly upregulated by injury in both genotypes were mRNA expression and protein level of ABCA1 transporter and APOJ, but not APOE. To identify gene-networks correlated to injury and APOE isoform, we performed Weighted Gene Co-expression Network Analysis. We determined that the network mostly correlated to TBI in animals expressing both isoforms is immune response with major hub genes including Trem2, Tyrobp, Clec7a and Cd68. We also found a significant increase of TREM2, IBA-1 and GFAP protein levels in the brains of injured mice. We identified a network representing myelination that correlated significantly with APOE isoform in both injury groups. This network was significantly enriched in oligodendrocyte signature genes, such as Mbp and Plp1. Our results demonstrate unique and distinct gene networks at this acute time point for injury and APOE isoform, as well as a network driven by APOE isoform across TBI groups.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.