ArticleHuman molecular genetics2014
Coding variants in TREM2 increase risk for Alzheimer's disease.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 3 of them syntheses that pooled it.
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Who cites it
209 citing papers in PubMed, 3 syntheses or guidelines pooled it, 317 citations in OpenAlex.
- Cytokines and immune biomarkers in neurodegeneration and cognitive function: A systematic review among individuals of African ancestry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Pooled it
- Pooled it
- The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective.Basic & clinical pharmacology & toxicology · 2026Review
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Acta neuropathologica · 2026Article
- Review
- Integrative genomics and single-cell CRISPRi screening dissect Alzheimer GWAS non-coding variants regulating TSPAN14.American journal of human genetics · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- Protective PLCG2 variants associate with a delayed onset of Alzheimer's disease among heterozygous APOE ε4 carriers.Alzheimer's research & therapy · 2026Article
- TREM2 activation by first-in-class direct small molecule agonists: DEL screening, optimization, biophysical validation, and functional characterization.European journal of medicinal chemistry · 2026Article
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- Alterations in the brain lipidome of Alzheimer's disease donors with rareBrain communications · 2026Article
- TREM2 as a central immunometabolic hub in Alzheimer's disease: linking microglial states, lipid stress, and disease-stage-specific intervention.Frontiers in immunology · 2026Review
- 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
- Genetic testing of common and rare variants in dementia patients from a memory clinic : Dementia-related genetic testing in memory clinic.Alzheimer's research & therapy · 2025Article
- Differential associations of APOE and TREM2 variants with glial fibrillary acidic protein and neurofilament light in plasma of UK Biobank participants support distinct disease mechanisms.Molecular psychiatry · 2025Article
149 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The triggering receptor expressed on myeloid 2 (TREM2) is an immune phagocytic receptor expressed on brain microglia known to trigger phagocytosis and regulate the inflammatory response. Homozygous mutations in TREM2 cause Nasu-Hakola disease, a rare recessive form of dementia. A heterozygous TREM2 variant, p.R47H, was recently shown to increase Alzheimer''s disease (AD) risk. We hypothesized that if TREM2 is truly an AD risk gene, there would be additional rare variants in TREM2 that substantially affect AD risk. To test this hypothesis, we performed pooled sequencing of TREM2 coding regions in 2082 AD cases and 1648 cognitively normal elderly controls of European American descent. We identified 16 non-synonymous variants, six of which were not identified in previous AD studies. Two variants, p.R47H [P = 9.17 × 10(-4), odds ratio (OR) = 2.63 (1.44-4.81)] and p.R62H [P = 2.36 × 10(-4), OR = 2.36 (1.47-3.80)] were significantly associated with disease risk in single-variant analyses. Gene-based tests demonstrate variants in TREM2 are genome-wide significantly associated with AD [PSKAT-O = 5.37 × 10(-7); OR = 2.55 (1.80-3.67)]. The association of TREM2 variants with AD is still highly significant after excluding p.R47H [PSKAT-O = 7.72 × 10(-5); OR = 2.47 (1.62-3.87)], indicating that additional TREM2 variants affect AD risk. Genotyping in available family members of probands suggested that p.R47H (P = 4.65 × 10(-2)) and p.R62H (P = 6.87 × 10(-3)) were more frequently seen in AD cases versus controls within these families. Gel electrophoresis analysis confirms that at least three TREM2 transcripts are expressed in human brains, including one encoding a soluble form of TREM2.
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Registered trials
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 OpenQuestion graph.