SynthesisThe New England journal of medicine2013
TREM2 variants in Alzheimer's disease.
Synthesis in The New England journal of medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,812 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,812 citing papers in PubMed, 2 syntheses or guidelines pooled it, 3,022 citations in OpenAlex.
- Genetic and environmental risk factors for dementia in African adults: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Pooled it
- The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial.Nature medicine · 2026Trial
- Trial
- Resveratrol Attenuates CSF Markers of Neurodegeneration and Neuroinflammation in Individuals with Alzheimer's Disease.International journal of molecular sciences · 2025Trial
- Article
- The lithium-magnesium-zinc axis under stress: regulation of N-glycosylation-linked proteostasis and Alzheimer's disease.Inflammopharmacology · 2026Review
- Early oligodendrocyte dysfunction signature in Alzheimer's disease: Insights from DNA methylomics and transcriptomics.Molecular psychiatry · 2026Article
- Context-dependent TREM2 signalling in myeloid cells: Molecular mechanisms and immunotherapeutic divergence in neurodegeneration and cancer.Clinical and translational medicine · 2026Review
- Metabolic reprogramming of microglia: Effects on development, disease, and therapeutic potential.Neural regeneration research · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- The Role of Herbal Medicines in Cognitive Impairment: A Narrative Review of Neuroprotective Mechanisms and Therapeutic Perspectives.Nutrients · 2026Review
- Small-Molecule NANT Therapeutics Targeting the Brain-Immune Axis in Alzheimer's Disease: Mechanisms, Clinical Progress, and Translational Challenges.Molecules (Basel, Switzerland) · 2026Review
- Batch- and Composition-Controlled Reanalysis of Bulk and Single-Nucleus Transcriptomes Reveals Co-Enrichment of Glial Complement and of Translational Signatures in Parkinson's Disease and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Article
- Alzheimer's Disease in the Era of Geroscience: Mechanisms, Biomarkers, and Therapeutic Prospects.Cells · 2026Review
- Uncovering the biological mechanisms of TREM2 with molecular simulations: A comprehensive review and perspective.Progress in biophysics and molecular biology · 2026Review
- Single-cell transcriptomics of human brain disorders.Molecular psychiatry · 2026Review
- Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.Nature genetics · 2026Article
- The TREM2 R47H variant is associated with liver-plasma-brain axis dyshomeostasis in the 5xFAD mouse model of Alzheimer's disease.Neurobiology of aging · 2026Article
- Pathological depositions in human disease: converging mechanisms in atherosclerosis, Alzheimer's disease, and related disorders.Molecular biomedicine · 2026Review
1,752 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundHomozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.
methodsWe used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice.
resultsWe found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P=0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P=0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease.
conclusionsHeterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.).
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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.