The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
R47H TREM2 variant increases risk of typical early‐onset Alzheimer's disease but not of prion or frontotemporal dementia
Open accessAbstract
Background: Rare TREM2 variants are significant risk factors for Alzheimer's disease (AD). Methods: We used next generation sequencing of the whole gene (n = 700), exon 2 Sanger sequencing (n = 2634), p.R47H genotyping (n = 3518), and genome wide association study imputation (n = 13,048) to determine whether TREM2 variants are risk factors or phenotypic modifiers in patients with AD (n = 1002), frontotemporal dementia (n = 358), sporadic (n = 2500), and variant (n = 115) Creutzfeldt‐Jakob disease (CJD). Results: We confirm only p.R47H as a risk factor for AD (odds ratio or OR = 2.19; 95% confidence interval or CI = 1.04‐4.51; P = .03). p.R47H does not significantly alter risk for frontotemporal dementia (OR = 0.81), variant or sporadic CJD (OR = 1.06 95%CI = 0.66‐1.69) in our cohorts. Individuals with p.R47H associated AD (n = 12) had significantly earlier symptom onset than individuals with no TREM2 variants (n = 551) (55.2 years vs. 61.7 years, P = .02). We note that heterozygous p.R47H AD is memory led and otherwise indistinguishable from “typical” sporadic AD. Conclusion: We find p.R47H is a risk factor for AD, but not frontotemporal dementia or prion disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“R47H is clearly linked to an increased risk of AD [40, 41]”
From TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation (2021) · cites this paper as [41]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,724
Wechsler Abbreviated Scale of Intelligence
Dumont, R., Willis, J. O., Veizel, K., & Zibulsky, J. (2014) · Wiley eBooks · doi:10.1002/9781118660584.ese2519 · Cited by 5,546
Manual for the Wechsler Adult Intelligence Scale.
Wechsler, D. (1955) · Psychological Corp. eBooks · Cited by 4,941
A nonparametric method for automatic correction of intensity nonuniformity in MRI data
Sled, J. G., Zijdenbos, A. P., & Evans, A. C. (1998) · IEEE Transactions on Medical Imaging · doi:10.1109/42.668698 · Cited by 4,731
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
Self-citationVariant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial
Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C., Eisner, L., Kirby, L., Rovira, M. B., Forette, F., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000159740.16984.3c · Cited by 1,329
Self-citationPaloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342259 · Cited by 683
Rademakers, R., Baker, M., Nicholson, A. M., Rutherford, N. J., Finch, N., Soto-Ortolaza, A., Lash, J., Wider, C., Wojtas, A., DeJesus-Hernandez, M., et al. (2012) · Nature Genetics · doi:10.1038/ng.1027 · Cited by 571
Self-citationLoss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts
Paloneva, J., Kestilä, M., Wu, J., Salminen, A., Böhling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B. H., Phillips, J. H., Pekkarinen, P., et al. (2000) · Nature Genetics · doi:10.1038/77153 · Cited by 460
Early-Versus Late-Onset Alzheimer's Disease: More than Age Alone
Koedam, E. L. G. E., Lauffer, V., van der Vlies, A. E., van der Flier, W. M., Scheltens, P., & Pijnenburg, Y. A. L. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-1337 · Cited by 452
Regulation of Microglial Proliferation during Chronic Neurodegeneration
Gómez-Nicola, D., Fransen, N. L., Suzzi, S., & Perry, V. H. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4440-12.2013 · Cited by 407
Rayaprolu, S., Mullen, B., Baker, M., Lynch, T., Finger, E., Seeley, W. W., Hatanpaa, K. J., Lomen-Hoerth, C., Kertesz, A., Bigio, E. H., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-19 · Cited by 404
Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.579 · Cited by 374
Self-citationBeck, E., Daniel, P. M., Matthews, W. B., Stevens, D. L., Alpers, M. P., Asher, D. M., Gajdusek, D. C., & Gibbs, C. J. (1969) · Brain · doi:10.1093/brain/92.4.699 · Cited by 260
TREM2and Neurodegenerative Disease
Reitz, C., & Mayeux, R. P. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1306509 · Cited by 258
The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2
Klünemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000160304.00003.ca · Cited by 254
Self-citationCardoso, M. J., Leung, K. K., Marc Modat, A., Shiva Keihaninejad, A., Cash, D. M., Barnes, J., Fox, N. C., & Sebastien Ourselin, A. (2013) · Medical Image Analysis · doi:10.1016/j.media.2013.02.006 · Cited by 246
Self-citationCNS manifestations of Nasu–Hakola disease
Bm, J., Autti, T., Raininko, R., Partanen, J., Salonen, O., Puranen, M., Hakola, P., & Haltia, M. (2001) · Neurology · doi:10.1212/wnl.56.11.1552 · Cited by 205
Cuyvers, E., Bettens, K., Philtjens, S., Langenhove, T. V., Gijselinck, I., van der Zee, J., Engelborghs, S., Vandenbulcke, M., Dongen, J. V., Geerts, N., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.009 · Cited by 185
Nasu, T., Tsukahara, Y., & Terayama, K. (1973) · Acta Pathologica Japonica · doi:10.1111/j.1440-1827.1973.tb01223.x · Cited by 184
Brain MAPS: An automated, accurate and robust brain extraction technique using a template library
Leung, K. K., Barnes, J., Marc Modat, A., Ridgway, G. R., Bartlett, J. W., Fox, N. C., & Sebastien Ourselin, A. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.12.067 · Cited by 181
Self-citationHeterozygous TREM2 mutations in frontotemporal dementia
Borroni, B., Ferrari, F., Galimberti, D., Nacmias, B., Barone, C., Bagnoli, S., Fenoglio, C., Piaceri, I., Archetti, S., Bonvicini, C., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.017 · Cited by 173
TREM2 is associated with the risk of Alzheimer's disease in Spanish population
Benitez, B. A., Cooper, B., Pastor, P., Jin, S.-C., Lorenzo, E., Cervantes, S., & Cruchaga, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.018 · Cited by 163
TREM2 R47H Variant as a Risk Factor for Early-Onset Alzheimer's Disease
Pottier, C. P., collaborators, G., Wallon, D., Rousseau, S., Rovelet‐Lecrux, A., Richard, A., Rollin‐Sillaire, A., Frébourg, T., Campion, D., & Hannequin, D. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122311 · Cited by 162
Hakola, H. P. (1972) · PubMed · Cited by 159
Clinical features and APOE genotype of pathologically proven early-onset Alzheimer disease
Balasa, M., Gelpí, E., Antonell, A., Rey, M. J., Sánchez‐Valle, R., Molinuevo, J. L., & Lladó, A. (2011) · Neurology · doi:10.1212/wnl.0b013e31821a44dd · Cited by 157
Giraldo, M., Lopera, F., Siniard, A. L., Corneveaux, J. J., Schrauwen, I., Carvajal, J., Muñoz, C., Ramirez-Restrepo, M., Gaiteri, C., Myers, A. J., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.02.016 · Cited by 147
Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils
Boyes, R. G., Gunter, J. L., Frost, C. D., Janke, A. L., Yeatman, T., Hill, D., Bernstein, M. A., Thompson, P. M., Weiner, M. W., Schuff, N. W., et al. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.10.026 · Cited by 144
Self-citationRuiz, A., Dols-Icardo, O., Bullido, M. J., Pastor, P., Rodríguez-Rodríguez, E., López de Munain, A., de Pancorbo, M. M., Pérez-Tur, J., Álvarez, V., Antonell, A., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.08.011 · Cited by 118
Most rapid cognitive decline in APOE ε4 negative Alzheimer's disease with early onset
van der Vlies, A. E., Koedam, E., Pijnenburg, Y. A. L., Twisk, J. W. R., Scheltens, P., & van der Flier, W. M. (2009) · Psychological Medicine · doi:10.1017/s0033291709005492 · Cited by 107
Benítez, B. A., & Cruchaga, C. (2013) · PubMed Central · doi:10.1056/nejmc1306509#sa4 · Cited by 64
Validation of next-generation sequencing technologies in genetic diagnosis of dementia
Beck, J., Pittman, A. M., Adamson, G., Campbell, T., Kenny, J., Houlden, H., Rohrer, J. D., de Silva, R., Shoai, M., Uphill, J. B., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.07.017 · Cited by 62
Self-citationTREM2 Risk Variant and Loss of Brain Tissue
Rajagopalan, P., Hibar, D. P., & Thompson, P. M. (2013) · Europe PMC (PubMed Central) · doi:10.1056/nejmc1306509#sa3 · Cited by 41
TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia
Lattante, S., Ber, I. L., Camuzat, A., Dayan, S., Godard, C., van Bortel, I., de Septenville, A. L., Ciura, S., Brice, A., & Kabashi, E. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.04.030 · Cited by 40
Tan, K. S., Libon, D. J., Rascovsky, K., Grossman, M., & Xie, S. X. (2013) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31827bdc6f · Cited by 36
前頭側頭葉変性症および前頭側頭葉変性症‐筋萎縮性側索硬化症のフランス人患者におけるUBQLN‐2のスクリーニング
Lattante, S., Ber, I. L., Camuzat, A., Brice, A., Kabashi, E., & Pariente, J. (2013) · Neurobiology of Aging · Cited by 1
Research works printed but not linked: 4
- Benitez B.A., 2013, TREM2 and neurodegenerative disease, N Engl J Med, 369, 1567
- Warrington E.K., 1984, Manual for the recognition memory test for words and faces
- Warrington E., 1991, The visual object and space perception battery
- Rajagopalan P., 2013, TREM2 and neurodegenerative disease, N Engl J Med, 369, 1565
Cited by
Sorted by citations
TREM2 — a key player in microglial biology and Alzheimer disease
Ulland, T. K., & Colonna, M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0072-1 · Cited by 735
New insights into the role of TREM2 in Alzheimer’s disease
Gratuze, M., Leyns, C. E. G., & Holtzman, D. M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0298-9 · Cited by 489
Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease
Kaur, D., Sharma, V., & Deshmukh, R. R. (2019) · Inflammopharmacology · doi:10.1007/s10787-019-00580-x · Cited by 503
TREM2, microglia, and neurodegenerative diseases
Yeh, F. L., Hansen, D. V., & Sheng, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.008 · Cited by 440
TREM2 variants: new keys to decipher Alzheimer disease pathogenesis
Colonna, M., & Wang, Y. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.7 · Cited by 418
Metadata
- Authors
- Slattery, C. F., Beck, J. A., Harper, L., Adamson, G., Abdi, Z., Uphill, J., Campbell, T., Druyeh, R., Mahoney, C. J., Rohrer, J. D., Kenny, J., Lowe, J., Leung, K. K., Barnes, J., Clegg, S. L., Blair, M., Nicholas, J. M., Guerreiro, R. J., Rowe, J. B., Ponto, C., Zerr, I., Kretzschmar, H., Gambetti, P., Crutch, S. J., Warren, J. D., Rossor, M. N., Fox, N. C., Collinge, J., Schott, J. M., & Mead, S.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Department of Neurodegenerative Disease MRC Prion Unit, UCL Institute of Neurology London UK
- MRC Prion Unit (GB)
- London School of Hygiene & Tropical Medicine (GB)
- University of Cambridge (GB)
- University of Göttingen (DE)
- Institut für Neuropathologie (DE)
- Case Western Reserve University (US)
- Corresponding author
- Mead, Simon
- ORCID
- Abdi, Zeinab
- Campbell, Tracy
- Mahoney, Colin J.
- Rohrer, Jonathan D.
- Kenny, Janna
- Lowe, Jessica
- Barnes, Josephine
- Clegg, Shona L.
- Blair, Melanie
- Nicholas, Jennifer M.
- Guerreiro, Rita J.
- Rowe, James B.
- Zerr, Inga
- Gambetti, Pierluigi
- Crutch, Sebastian J.
- Warren, Jason D.
- Rossor, Martin N.
- Fox, Nick C.
- Collinge, John
- Schott, Jonathan M.
- Mead, Simon
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2014-08-23
- Volume
- 10
- Issue
- 6
- Pages
- 602
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC4627504
- OpenAlex
- W1973742293
- Cited by
- 119
- References
- 40
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 5 · 2023: 8 · 2022: 14 · 2021: 12 · 2020: 7 · 2019: 14 · 2018: 11 · 2017: 13 · 2016: 7 · 2015: 10
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- GRO (submittedVersion)
- Funders
- Medical Research Council
- Alzheimer's Research
- NIHR Queen Square Dementia Biomedical Research Unit
- Leonard Wolfson Experimental Neurology Centre
- University College London Hospitals NHS Trust Biomedical Research Centre
- MRC (G0000934)
- Wellcome Trust (068545/Z/02, 088324)
- Brain Research Trust
- Wellcome Trust Senior Clinical Fellowship (091673/Z/10/Z)
- NIHR Cambridge Biomedical Research Centre
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TREM2
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Arginine, Brain, Exons, Female, Genotype, Histidine, Humans, Creutzfeldt-Jakob Syndrome, Male, Membrane Glycoproteins, Middle Aged, Phenotype, Receptors, Immunologic, Risk Factors, Genetic Variation, Cohort Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Frontotemporal Dementia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
