ArticleClinical epigenetics2016
TREM2 upregulation correlates with 5-hydroxymethycytosine enrichment in Alzheimer's disease hippocampus.
Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Gain-of-function Modulation of TREM2 and its Impact on Amyloid-β and Tau Pathologies in Alzheimer's Disease: A Systematic Review and Meta-analysis of Animal Studies.Molecular neurobiology · 2026Pooled it
- The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.PloS one · 2016Pooled it
- The Substrate-Engine Model of Ferroptosis: Stage-Specific Targeting of Acyl-CoA Synthetase Long-Chain Family Member 4 and 5‑Lipoxygenase in Alzheimer's Disease.ACS pharmacology & translational science · 2026Review
- TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026Review
- Triggering receptor expressed on myeloid cell family in atherosclerosis: from mechanisms to intervention strategies.Cell communication and signaling : CCS · 2026Review
- Role of TREM2 in neuroinflammation regulation: mechanisms, disease associations, and therapeutic translation advances.Journal of translational medicine · 2025Review
- Mechanistic Disruption of the TREM2-DAP12 Transmembrane Complex by Alzheimer's Disease Mutations: A Multiscale Simulation Study.Journal of chemical information and modeling · 2025Article
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- TREM2 in MASH: integrating lipid metabolism and immune response.Frontiers in immunology · 2025Review
- The Promise of Epigenetic Editing for Treating Brain Disorders.Sub-cellular biochemistry · 2025Review
- A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer's disease based on the neuroinflammatory.Chinese medicine · 2024Review
- Association of Blood-Based DNA Methylation Markers With Late-Onset Alzheimer Disease: A Potential Diagnostic Approach.Neurology · 2023Article
- Article
- Review
- TREM2 gene expression associations with Alzheimer's disease neuropathology are region-specific: implications for cortical versus subcortical microglia.Acta neuropathologica · 2023Article
- TREM2 Expression and Amyloid-Beta Phagocytosis in Alzheimer's Disease.International journal of molecular sciences · 2023Article
- The effects and potential of microglial polarization and crosstalk with other cells of the central nervous system in the treatment of Alzheimer's disease.Neural regeneration research · 2023Review
- Review
- Review
- Utility of DNA Methylation as a Biomarker in Aging and Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent genome-wide association studies revealed TREM2 rs75932628-T variant to be associated with Alzheimer's disease (AD) and other neurodegenerative diseases. However, the role that TREM2 plays in sporadic AD is largely unknown. Our aim was to assess messenger RNA (mRNA) expression levels and DNA methylation profiling of TREM2 in human hippocampus in AD brain. We measured TREM2 mRNA levels in the hippocampus in a cohort of neuropathologically confirmed controls and pure AD cases showing no other protein deposits than β-amyloid and phosphorylated tau. We also examined DNA methylation levels in the TREM2 transcription start site (TSS)-associated region by bisulfite cloning sequencing and further extended the study by measuring 5-hydroxymethycytosine (5hmC) enrichment at different regions of TREM2 by 5hmC DNA immunoprecipitation combined with real-time qPCR.
resultsA 3.4-fold increase in TREM2 mRNA levels was observed in the hippocampus of AD cases compared to controls (p = 1.1E-05). Interestingly, TREM2 methylation was higher in AD cases compared to controls (76.2 % ± 15.5 versus 57.9 % ± 17.1; p = 0.0016). Moreover, TREM2 mRNA levels in the AD hippocampus correlated with enrichment in 5hmC at the TREM2 gene body (r = 0.771; p = 0.005).
conclusionsTREM2 mRNA levels are increased in the human hippocampus in AD cases compared to controls. DNA methylation, and particularly 5hmC, may be involved in regulating TREM2 mRNA expression in the AD brain. Further studies are guaranteed to investigate in depth the role of 5hmC in AD and other neurodegenerative disorders.
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