Evidence map›Paper›PMID 25936935›Full record

SynthesisAlzheimer's & dementia : the journal of the Alzheimer's Association2015

The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease.

Christina M Lill, Aina Rengmark, Lasse Pihlstrøm, Isabella Fogh, Aleksey Shatunov, Patrick M Sleiman, Li-San Wang, Tian Liu, Christina F Lassen, Esther Meissner and 42 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 5 pooled it
15.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 5 syntheses or guidelines pooled it, 202 citations in OpenAlex.

  1. Pooled it
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  6. Trial
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  10. A novel homozygousThe Journal of international medical research · 2026
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  18. Unraveling the Immune Puzzle: Role of Immunomodulation in Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
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44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

52 authors at 20 institutions in 9 countries.

Christina M LillPlatform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany. Electronic address: christina.lill@gmx.de.
Aina RengmarkDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Lasse PihlstrømDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Isabella FoghDepartment of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK.
Aleksey ShatunovDepartment of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK.
Patrick M SleimanCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Li-San WangDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Tian LiuMax Planck Institute for Human Development, Berlin, Germany.
Christina F LassenInstitute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
Esther MeissnerDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Panos AlexopoulosDepartment of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.
Andrea CalvoRita Levi Montalcini Department of Neuroscience, ALS Center, University of Torino, Torino, Italy.
Adriano ChioRita Levi Montalcini Department of Neuroscience, ALS Center, University of Torino, Torino, Italy; Neuroscience Institute of Turin, Turin, Italy.
Nil DizdarDepartment of Neurology, Linköping University, Linköping, Sweden.
Frank FaltracoDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University of Frankfurt, Frankfurt, Germany.
Lars ForsgrenDepartment of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
Julia KirchheinerDepartment of Neurology, University of Ulm, Ulm, Germany.
Alexander KurzDepartment of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.
Jan P LarsenThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.
Maria LiebschDepartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Jan LinderDepartment of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
Karen E MorrisonSchool of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Neurosciences Division, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Hans NissbrandtDepartment of Pharmacology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Markus OttoDepartment of Neurology, University of Ulm, Ulm, Germany.
Jens PahnkeDepartment of Neuro-/Pathology, University of Oslo and Oslo University Hospital, Oslo, Norway; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Amanda PartchDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Gabriella RestagnoDepartment of Clinical Pathology, Molecular Genetics Unit, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy.
Dan RujescuDepartment of Psychiatry, University of Halle-Wittenberg, Halle, Germany.
Cathrin SchnackDepartment of Neurology, University of Ulm, Ulm, Germany.
Christopher E ShawDepartment of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK.
Pamela J ShawDepartment of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, UK.
Hayrettin TumaniDepartment of Neurology, University of Ulm, Ulm, Germany.
Ole-Bjørn TysnesDepartment of Neurology, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Otto ValladaresDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Vincenzo SilaniDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milano, Italy; Department of Pathophysiology and Tranplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milano, Italy.
Leonard H van den BergDepartment of Neurology, Neuromuscular Diseases Brain Center Rudolf Magnus, Netherlands ALS Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Wouter van RheenenDepartment of Neurology, Neuromuscular Diseases Brain Center Rudolf Magnus, Netherlands ALS Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Jan H VeldinkDepartment of Neurology, Neuromuscular Diseases Brain Center Rudolf Magnus, Netherlands ALS Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Ulman LindenbergerMax Planck Institute for Human Development, Berlin, Germany.
Elisabeth Steinhagen-ThiessenInterdisciplinary Metabolic Center, Lipids Clinic, Charité University Medicine, Berlin, Germany.
SLAGEN Consortium
Stefan TeipelGerman Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
Robert PerneczkyDepartment of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK; West London Cognitive Disorders Treatment and Research Unit, West London Mental Health Trust, London, UK.
Hakon HakonarsonCenter for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Harald HampelAXA Research Fund & UPMC Chair, Paris, France; Département de Neurologie, Sorbonne Universités, Université Pierre et Marie Curie, Institut de la Mémoire et de la Maladie d'Alzheimer & Institut du Cerveau et de la Moelle épinière (ICM), Hôpital de la Pitié-Salpétrière, Paris, France.
Christine A F von ArnimDepartment of Neurology, University of Ulm, Ulm, Germany.
Jørgen H OlsenInstitute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark.
Vivianna M Van DeerlinDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Ammar Al-ChalabiDepartment of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK.
Mathias ToftDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Beate RitzDepartment of Epidemiology and Environmental Sciences, School of Public Health, University of California, Los Angeles, CA, USA.
Lars BertramPlatform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Neuroepidemiology and Ageing Research Unit, School of Public Health, Faculty of Medicine, The Imperial College of Science, Technology, and Medicine, London, UK.
Universität Ulm · DEKing's College London · GBUniversity of Pennsylvania · USOslo University Hospital · NOUniversity Medical Center Utrecht · NLChildren's Hospital of Philadelphia · USDanish Cancer Society · DKMax Planck Institute for Human Development · DEMax Planck Institute for Molecular Genetics · DETechnical University of Munich · DEUmeå University · SEUniversity of Lübeck · DEAzienda Ospedaliera Citta' della Salute e della Scienza di Torino · ITCharité - Universitätsmedizin Berlin · DEGoethe University Frankfurt · DEHaukeland University Hospital · NOImperial College London · GBInstitute for Integrative and Experimental Genomics · DELinköping University · SELos Angeles County Department of Public Health · US

Funding

Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Trevor M Penning · 2006 to 2026
$35.3M
Registry Study of Parkinsons Disease in DenmarkR01ES013717 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2006 to 2010
$4.5M
Medical Research Council G0500289Medical Research Council G0900688Medical Research Council MC_G1000733Medical Research Council MR/L021803/1Medical Research Council MR/L501529/1NIA NIH HHS P01 AG017586NIEHS NIH HHS P30 ES013508NIEHS NIH HHS R01 ES013717NIEHS NIH HHS R01ES013717Wellcome Trust 089701
6 · The paper itself

Abstract

A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aβ42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.

Indexed as

Genetic Predisposition to DiseaseAgedAllelesAlzheimer DiseaseAmyotrophic Lateral SclerosisCase-Control StudiesFemaleFrontotemporal Lobar DegenerationGenotypeHumansMaleMembrane GlycoproteinsMiddle AgedNeurodegenerative DiseasesParkinson DiseaseQuantitative Trait LociMembrane GlycoproteinsReceptors, Immunologictau ProteinsTREM2 protein, humanAlzheimer diseaseAmyotrophic lateral sclerosisFrontotemporal lobar degenerationGenetic associationGWASImputationMeta-analysisNeurodegenerative diseaseParkinson diseaseR47HRare variantrs75932628TREM2

Identifiers

PMID25936935
PMCPMC4627856
OpenAlexW2055995786

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Registered trials

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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 OpenQuestion graph.