The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia–like Syndrome Without Bone Involvement
Open accessAbstract
OBJECTIVE: To identify new genes and risk factors associated with frontotemporal dementia (FTD). Several genes and loci have been associated with different forms of FTD, but a large number of families with dementia do not harbor mutations in these genes. DESIGN: Whole-exome sequencing and whole-genome genotyping were performed in all patients. Genetic variants obtained from whole-exome sequencing were integrated with the data obtained from whole-genome genotyping. SETTING: Database of the Behavioral Neurology Outpatient Clinic of the Department of Neurology, Istanbul Faculty of Medicine, Istanbul, Turkey. PATIENTS Forty-four Turkish patients with an FTD-like clinical diagnosis were included in the study. Relatives were screened when appropriate. MAIN OUTCOME MEASURE: Mutations in the triggering receptor expressed on myeloid cells 2 gene (TREM2). RESULTS: In 3 probands with FTD-like disease, we identified different homozygous mutations in TREM2 that had previously been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). None of these 3 patients had a typical clinical presentation of PLOSL: they presented with behavioral change and subsequent cognitive impairment and motor features but without any bone cysts or bone-associated phenotypes. Imaging showed white matter abnormalities as well as frontal atrophy in all 3 patients. CONCLUSIONS: Our results show that TREM2 is responsible for an unexpectedly high number of dementia cases in our cohort, suggesting that this gene should be taken into account when mutations in other dementia genes are excluded. Even for complex syndromes such as dementia, exome sequencing has proven to be a rapid and cost-effective tool to identify genetic mutations, allowing for the association of clinical phenotypes with unexpected molecular underpinnings.
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
“In particular, there is converging evidence for the role of neuroinflammation in neurodegenerative dementias, including FTD, from genetic associations (Guerreiro et al., 2013; Rayaprolu et al., 2013; Broce et al., 2018), CSF (Sjogren et al., 2004; Woollacott et al., 2018), epidemiology (Miller et al., 2013, 2016), post-mortem tissue (Venneti et al., 2008; Lant et al., 2014) and animal models”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Guerreiro et al., 2013
In the citing paper
“Nonsense or missense mutations in TREM2 have been identified in several families with FTD.343–345”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [344]
In the citing paper
“Homozygous TREM2 p.T66M mutation has also been identified to cause FTD-like syndrome.344”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [344]
In the citing paper
“In addition to the R47H variant, further TREM2 variants have been revealed to be risk factors of AD or other CNS diseases, such as R62H (8,20), H157Y (25), Q33X, T66M and Y38C (26,27).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [27]
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
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,457
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G. P., Onyike, C. U., et al. (2011) · Brain · doi:10.1093/brain/awr179 · Cited by 5,221
Self-citationFrontotemporal lobar degeneration: A consensus on clinical diagnostic criteria
Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P. H., Albert, M., et al. (1998) · Neurology · doi:10.1212/wnl.51.6.1546 · Cited by 5,047
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409
Self-citationAssociation of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Self-citationWeıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 378
Frontotemporal dementia spectrum: first genetic screen in a Greek cohort
Ramos, E. M., Koros, C., Dokuru, D. R., Berlo, V. V., Κroupis, C., Wojta, K. J., Wang, Q., Andronas, N., Matsi, S., Beratis, I., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.10.029 · Cited by 25
Yanaizu, M., Sakai, K., Tosaki, Y., Kino, Y., & Satoh, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-25204-2 · Cited by 23
SWI and phase imaging reveal intracranial calcifications in the P301L mouse model of human tauopathy
Ni, R., Zarb, Y., Kuhn, G. A., Müller, R., Yundung, Y., Nitsch, R. M., Kulic, L., Keller, A., & Klohs, J. (2020) · Magnetic Resonance Materials in Physics, Biology and Medicine · doi:10.1007/s10334-020-00855-3 · Cited by 24
Luo, L., Chen, J., Wu, Q., Yuan, B., Hu, C., Yang, T., Wei, H., & Li, T. (2023) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2023.104090 · Cited by 24
How understudied populations have contributed to our understanding of Alzheimer’s disease genetics
Dehghani, N., Brás, J., & Guerreiro, R. J. (2021) · Brain · doi:10.1093/brain/awab028 · Cited by 25
Self-citationMehrjoo, Z., Najmabadi, A., Abedini, S. S., Mohseni, M., Kamali, K., Najmabadi, H., & Khorshid, H. R. K. (2015) · Medical Principles and Practice · doi:10.1159/000430842 · Cited by 24
TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting
Yang, H.-W., Kim, D., Yang, Y., Bagyinszky, E., & An, S. S. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157057 · Cited by 26
“The homozygous loss-of-function mutations of TREM2 have been verified to play a role in an autosomal recessive disease called Nasu–Hakola disease (NHD), which affects the brain and bones [45–47].”
Tau-Mediated Dysregulation of Neuroplasticity and Glial Plasticity
Koller, E. J., & Chakrabarty, P. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00151 · Cited by 23
The Birth of the Modern Era of Parkinson’s Disease Genetics
Singleton, A., Hardy, J., & Gasser, T. (2017) · Journal of Parkinson s Disease · doi:10.3233/jpd-179009 · Cited by 22
“In thinking back over the sheer scale of work and effort that we and others placed in this area, it is perhaps surprising that only a small number of genes were identified for PD during this time; however, the influence of these findings was great.”
BackgroundSelf-citationA Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach
Alshehri, R. S., Abuzinadah, A. R., Alrawaili, M. S., Alotaibi, M. K., Alsufyani, H. A., Alshanketi, R. M., & Alshareef, A. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252010900 · Cited by 23
“TREM2 has been shown to stimulate astrogliosis in various NDs [191,192].”
BackgroundVarnum, M. M., Clayton, K. A., Yoshii-Kitahara, A., Yonemoto, G., Koro, L., Ikezu, S., & Ikezu, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.759159 · Cited by 22
Wang, R., Zhou, Z., Wang, D., Zhao, Q., Zhang, C., Liu, C., Zhao, H., Yuan, C., Yuan, D., & Wang, T. (2021) · Food & Function · doi:10.1039/d0fo02946g · Cited by 22
Current understanding on TREM-2 molecular biology and physiopathological functions
Bharadwaj, S., Groza, Y., Mierzwicka, J. M., & Malý, P. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112042 · Cited by 23
Differential interaction with TREM2 modulates microglial uptake of modified Aβ species
Joshi, P., Riffel, F., Satoh, K., Enomoto, M., Qamar, S., Scheiblich, H., Villacampa, N., Kumar, S., Theil, S., Parhizkar, S., et al. (2021) · Glia · doi:10.1002/glia.24077 · Cited by 21
The innate immune response in tauopathies
Johnson, A. M., & Lukens, J. R. (2023) · European Journal of Immunology · doi:10.1002/eji.202250266 · Cited by 22
Galectin‐3 is upregulated in frontotemporal dementia patients with subtype specificity
Borrego‐Écija, S., Pérez‐Millan, A., Antonell, A., Fort‐Aznar, L., Tilki, E. K., León‐Halcón, A., Lladó, A., Molina‐Porcel, L., Balasa, M., Juncà‐Parella, J., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13536 · Cited by 22
Frontotemporal Dementia and Chorea Associated with a Compound Heterozygous TREM2 Mutation
Redaelli, V., Salsano, E., Colleoni, L., Corbetta, P., Tringali, G., Sole, A. D., Giaccone, G., & Rossi, G. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180018 · Cited by 20
“In particular, in cases clinically defined as FTD-like and showing leukoencephalopathy at brain imaging, mutations in triggering receptor expressed on myeloid cells 2 ( TREM 2 ) gene have been identified [4].”
InfluentialMultimerization of TREM2 is impaired by Alzheimer's disease–associated variants
Dean, H. B., Greer, R. A., Yang, S., Elston, D. S., Brett, T. J., Roberson, E. D., & Song, Y. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14124 · Cited by 20
TREM2 in Neurodegenerative Diseases: Mechanisms and Therapeutic Potential
Li, L., Zheng, X., Ma, H., Zhu, M., Li, X., Sun, X., & Feng, X. (2025) · Cells · doi:10.3390/cells14171387 · Cited by 22
“Established mutations in TREM2 ’s extracellular domain associated with NHD include Y38C , W50C , T66M and V126G [58,60,144,145].”
Ayyubova, G. (2023) · European Journal of Neuroscience · doi:10.1111/ejn.15914 · Cited by 21
The genetic basis of multiple system atrophy
Tseng, F. S., Foo, J. Q. X., Mai, A. S., & Tan, E. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-03905-1 · Cited by 26
Ng, A. S. L., Tan, Y. J., Zhao, Y., Tandiono, M., Chew, E. G. Y., Dominguez, J. C., Macas, M., Ng, E., Hameed, S., Ting, S. K. S., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.04.003 · Cited by 19
Inflammatory markers of CHMP2B-mediated frontotemporal dementia
Roos, P., von Essen, M. R., Nielsen, T. T., Johannsen, P., Stokholm, J., Bie, A. S., Waldemar, G., Simonsen, A. H., Heslegrave, A., Zetterberg, H., et al. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.08.009 · Cited by 23
Joshi, P., Riffel, F., Kumar, S., Villacampa, N., Theil, S., Parhizkar, S., Haass, C., Colonna, M., Heneka, M. T., Arzberger, T., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01263-x · Cited by 18
The Role of Microglia in Inherited White-Matter Disorders and Connections to Frontotemporal Dementia
Sirkis, D. W., Bonham, L. W., & Yokoyama, J. S. (2021) · The Application of Clinical Genetics · doi:10.2147/tacg.s245029 · Cited by 21
Advances in Genetic and Molecular Understanding of Alzheimer’s Disease
Ibáñez, L., Cruchaga, C., & Fernández, M. V. (2021) · Genes · doi:10.3390/genes12081247 · Cited by 20
“The later discovery of loss-of-function variants in TREM2 provided scientists with particular targets to focus on in the study of the immune response in AD pathology [63,64].”
BackgroundChen, Y., Chen, X., Guo, X., Song, W., Cao, B., Wei, Q., Ou, R., Zhao, B., & Shang, H. (2015) · Neurological Sciences · doi:10.1007/s10072-015-2279-x · Cited by 18
“Studies also identified a significant association with diseased risk for frontotemporal dementia (FTD) [4, 12],”
BackgroundNiche-specific therapeutic targeting of myeloid cells in the central nervous system
Frosch, M., & Prinz, M. (2025) · Immunity · doi:10.1016/j.immuni.2025.03.016 · Cited by 17
Sexton, C. E., Solis, M., Aharon‐Peretz, J., Alexopoulos, P., Apostolova, L. G., Bayen, É., Birkenhager, B., Cappa, S. F., Constantinidou, F., Fortea, J., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12588 · Cited by 20
Immunological aspects of central neurodegeneration
Niso‐Santano, M., Fuentes, J. M., & Galluzzi, L. (2024) · Cell Discovery · doi:10.1038/s41421-024-00666-z · Cited by 17
“Mutations in C9orf72-SMCR8 complex subunit ( C9Orf72 ), MAPT , TREM2 and granulin precursor ( GRN ) have been associated with familial variants of the disease 160 – 163 , but sporadic FTD accounts for > 60% of FTD cases 164 .”
BackgroundCerebral amyloid angiopathy and the immune system
Munsterman, D., Falcione, S. R., Long, R., Boghozian, R., Joy, T., Camicioli, R. M., Smith, E. E., & Jickling, G. C. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13826 · Cited by 16
Neuroinflammation as a therapeutic target in neurodegenerative diseases
Gordon, R., & Woodruff, T. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805120-7.00003-8 · Cited by 19
Neuroimmune interactions in Alzheimer's disease—New frontier with old challenges?
Prokop, S., Lee, V. M. ‐., & Trojanowski, J. Q. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.10.002 · Cited by 17
Jones, B. L. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.254 · Cited by 17
Su, W., Shi, Z., Liu, S., Wang, X., Liu, S., & Ji, Y. (2018) · Annals of Human Genetics · doi:10.1111/ahg.12241 · Cited by 16
Mutations in TYROBP are not a common cause of dementia in a Turkish cohort
Darwent, L., Carmona, S., Lohmann, E., Güven, G., Kun‐Rodrigues, C., Bılgıç, B., Hanağası, H. A., Gurvit, H. I., Erginel‐Ünaltuna, N., Pak, M., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.06.019 · Cited by 16
“The same type of mutations in TREM2 were also found to cause frontotemporal dementia (FTD) without the typical bone phenotypes found in PLOSL (Guerreiro et al., 2013a), and heterozygous rare variants have been shown to modulate the risk of Alzheimer's disease (Guerreiro et al., 2013b; Jonsson et al., 2013).”
BackgroundInfluentialSelf-citationRole of triggering receptor expressed on myeloid cells 2 (TREM2) in neurodegenerative dementias
Shafi, S., Singh, A., Ibrahim, A. M., Alhajri, N., Izneid, T. A., & Pottoo, F. H. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15215 · Cited by 15
Pepłońska, B., Berdyński, M., Mandecka, M., Barczak, A. K., Kuźma‐Kozakiewicz, M., Barcikowska, M., & Żekanowski, C. (2018) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2018.1451894 · Cited by 16
Kober, D. L., Wanhainen, K. M., Johnson, B., Randolph, D. T., Holtzman, M. J., & Brett, T. J. (2014) · Protein Expression and Purification · doi:10.1016/j.pep.2014.01.015 · Cited by 16
“Additional variants including D87N and T96K have been linked to AD development [1] and two other point mutations in TREM-2 (Y38C and T66M) have been linked to the development of frontotemporal dementia (FTD) [8–11].”
BackgroundTREM2 variants as a possible cause of frontotemporal dementia with distinct neuroimaging features
Samanci, B., Bilgiç, B., Gelişin, Ö., Tepgeç, F., Guven, G., Tüfekçioğlu, Z., Alaylıoğlu, M., Hanagasi, H. A., Gürvit, H., Guerreiro, R., et al. (2021) · European Journal of Neurology · doi:10.1111/ene.14908 · Cited by 14
“A limited number of case reports described neuroimaging findings in NHD patients presenting with neurological symptoms [5,9,32,33] three findings mentioned above were present in all these cases.”
BackgroundSelf-citationThe triggering receptor expressed on myeloid cells 2–apolipoprotein E signaling pathway in diseases
Lyu, S., Lan, Z., & Li, C. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002167 · Cited by 13
“1, in the TREM gene cluster.([30,31]) The structural components of TREMs include an extracellular immunoglobulin-like domain, a transmembrane domain, and a small cytoplasmic tail.”
BackgroundChen, X., Chen, Y., Wei, Q., Guo, X., Cao, B., Ru⁃wei, O., Zhao, B., & Shang, H. (2015) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2015.05.010 · Cited by 13
“R47H) as a risk factor for AD, suggesting that the protein plays an important role in neurodegeneration [6,19,20].”
BackgroundCharting Frontotemporal Dementia: From Genes to Networks
Filippi, M., Agosta, F., & Ferraro, P. M. (2015) · Journal of Neuroimaging · doi:10.1111/jon.12316 · Cited by 14
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer’s disease
Martiskainen, H., Willman, R.-M., Harju, P., Heikkinen, S., Heiskanen, M., Müller, S. A., Sinisalo, R., Takalo, M., Mäkinen, P. M., Kuulasmaa, T., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00830-3 · Cited by 14
“Interestingly, some deleterious biallelic TREM2 variants lead to frontotemporal dementia without bone involvement [6, 7].”
Glycolytic metabolism supports microglia training during age-related neurodegeneration
Camacho‐Morales, A. (2022) · Pharmacological Reports · doi:10.1007/s43440-022-00363-2 · Cited by 11
Fluid Biomarkers of Frontotemporal Lobar Degeneration
van der Ende, E. L., & Swieten, J. C. V. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_9 · Cited by 11
Lysosomal Storage Disorders and Iron
Brás, J. (2013) · International review of neurobiology · doi:10.1016/b978-0-12-410502-7.00012-0 · Cited by 11
Self-citationTREM2 in Regulating Macrophage Inflammatory Responses and Disease Pathogenesis
Medd, M. M. (2024) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2024054889 · Cited by 12
Microglial Responses to Alzheimer's Disease Pathology: Insights From “Omics” Studies
Reid, A. N., Jayadev, S., & Prater, K. E. (2025) · Glia · doi:10.1002/glia.24666 · Cited by 10
“…genetics studies culminated in the discovery of both rare disease variants and common risk loci, all of which were located within genes expressed exclusively in microglia or other brain-associated myeloid cells (Guerreiro et al. 2013; Hollingworth et al. 2011; Jonsson et al. 2013; Naj et al. 2011).”
Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau
Iyer, A. K., Vermunt, L., Mirfakhar, F. S., Minaya, M., Acquarone, M., Koppisetti, R. K., Renganathan, A., You, S., Danhash, E., Schache, K. J., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03073-2 · Cited by 14
“Homozygous mutations in the gene encoding TREM2 , an activating receptor exclusively expressed in microglia in the CNS, are clinically associated with FTLD-like syndrome [101].”
Nájera, G. S., Narganes-Carlón, D., & Crowther, D. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-94897-9 · Cited by 9
Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2
Ogonowski, N. S., Santamaría‐García, H. A., Báez, S., López, A., Laserna, A., Garcia-Cifuentes, E. R., Ayala‐Ramírez, P., Zarante, I., Suárez‐Obando, F., Reyes, P. A., et al. (2023) · Journal of Medical Genetics · doi:10.1136/jmg-2022-108627 · Cited by 11
Immunohistochemical characterization of CD33 expression on microglia in Nasu‐Hakola disease brains
Satoh, J., Kino, Y., Motohashi, N., Ishida, T., Yagishita, S., Jinnai, K., Arai, N., Nakamagoe, K., Tamaoka, A., Saito, Y., et al. (2015) · Neuropathology · doi:10.1111/neup.12222 · Cited by 10
“Importantly, a panel of homozygous mutations, comprised of Q33X, Y38C and T66M, are also identified in Turkish patients presenting with frontotemporal dementia (FTD).(37) These observations propose a molecular link in the pathogenesis among AD, FTD and NHD, based on aberrant phagocytic function of microglia attributab…”
BackgroundBustos, C., Ortega-Rojas, J., Mahecha, M. F., Arboleda, G., Vásquez, R., Pardo, R., & Arboleda, H. (2018) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000275 · Cited by 10
Sassi, C., Capozzo, R., Hammer, M. B., Zecca, C., Federoff, M., Blauwendraat, C., Bernstein, N., Ding, J., Gibbs, J. R., Price, T. R., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-85494-x · Cited by 9
Self-citationFernández‐Vega, I., de Heredia-Goñi, K. P., Santos‐Juanes, J., Goñi-Imízcoz, M., Zaldumbide, L., Zarranz, J. J., & Ferrer, I. (2015) · Histopathology · doi:10.1111/his.12741 · Cited by 10
“Genetic studies have also been performed in suspected cases and in series of patients with leucodystrophy of unknown origin.(32,33) CSF1R mutations are the hallmark of the POLD/HDLS/ALSP spectrum, but it is not known whether old reported cases bore CSF1R mutations, and whether CSF1R mutations, although markers of ALSP…”
BackgroundChee, K. Y., Gaillard, F., Velakoulis, D., Ang, C. L., Chin, L.-K., & Ariffin, R. (2017) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867417707821 · Cited by 10
“TREM2 mutations leading to early-onset dementia without bone cyst formation have so far been reported only in a single Lebanese family (Chouery et al., 2008) and three Turkish families (Guerreiro et al., 2013).”
BackgroundLok, H. C., & Kwok, J. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052541 · Cited by 10
Haploinsufficiency and Alzheimer’s Disease: The Possible Pathogenic and Protective Genetic Factors
Bagyinszky, E., & An, S. S. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252211959 · Cited by 10
Diebold, M., Fehrenbacher, L., Frosch, M., & Prinz, M. (2023) · European Journal of Immunology · doi:10.1002/eji.202250234 · Cited by 10
Li, X., Sun, Y., Gong, L., Li, Z., Chen, K., Zhou, Y. F., Gu, Y., Xu, Y., Guo, Q., Hong, Z., et al. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.01.009 · Cited by 9
Schwarz, H., Bässler, S., Balta, D., Socher, E., Zunke, F., & Arnold, P. (2022) · Behavioural Brain Research · doi:10.1016/j.bbr.2022.113977 · Cited by 8
Neurodegenerative Disease Risk in Carriers of Autosomal Recessive Disease
Vieira, S. R. L., & Morris, H. R. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.679927 · Cited by 10
“Y38C variants, residing in the Ig fold, lead to deficits in TREM2 protein folding, maturation, and expression (145, 146).”
BackgroundBianchin, M. M., Abujamra, A. L., & Izquierdo, I. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.453 · Cited by 9
Pillai, J. P., Sung, K., & Wu, C. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.01.024 · Cited by 7
“However, two heterozygotes demonstrated these symptoms, consistent with NHD [28].”
Unveiling the impact of TREM-2+ Macrophages in metabolic disorders
Contreras, M., Matos, A. D. O., Dantas, P. H. D. S., Neto, J. R. D. C., Silva‐Sales, M., & Sales‐Campos, H. (2024) · Cellular Immunology · doi:10.1016/j.cellimm.2024.104882 · Cited by 10
Hernández, I., Rosende‐Roca, M., Alegret, M., Mauleón, A., Espinosa, A., Vargas, L., Sotolongo‐Grau, Ó., Tárraga, L., Boada, M., & Ruiz, A. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132432 · Cited by 8
“Interestingly, genetic analysis of familiar cases of FTD has revealed mutations in multiple loci including GRN [13, 14] and MAPT [15] genes, both very close on chromosome 17, but also in CHMP2B [16], UBQLN2 [17], SQSTM1 [18], or TREM2 [19] genes.”
Soluble TREM2 in body fluid in Alzheimer’s disease and Parkinson’s disease
Gu, L., Shu, H., & Wang, Y. (2023) · Neurological Sciences · doi:10.1007/s10072-023-06729-5 · Cited by 7
“The gene encoding the TREM2, a signaling receptor associated with microglial activation, is considered to be related to some neurodegenerative disorders, including AD [5], frontotemporal (FTD)-like dementia [6], and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy [7].”
BackgroundAtypical findings: Atypical parkinsonian syndromes or Atypical parkinsonian syndromes look-alikes
Çalıkuşu, F. Z., Akkuş, S., Kızılkılıç, E. K., Poyraz, B. Ç., Altunç, A. T., Kızıltan, G., & Gündüz, A. (2023) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2023.107975 · Cited by 8
Ramakrishnan, S., Arshad, F., Bs, K., Pon, A. G., Bosco, S., Kumar, S., Chidambaram, H., Chinnathambi, S. C. B., Kulanthaivelu, K., Arunachal, G., et al. (2024) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000538145 · Cited by 8
Evaluation of the Clinical Features Accompanied by the Gene Mutations
Eryılmaz, I. E., Bakar, M., Egelí, Ü., Çeçener, G., Yurdacan, B., Çolak, D. K., & Tunca, B. (2021) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000437 · Cited by 7
Crews, F. T., Qin, L., Coleman, L. G., Vidrascu, E. M., & Vetreno, R. P. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106156 · Cited by 7
Santamaría‐García, H. A., Ogonowski, N. S., Báez, S., Palacio, N., Reyes, P. A., Schulte, M., López, A., Matallana, D., & Ibáñez, A. M. (2022) · BMC Neurology · doi:10.1186/s12883-022-02954-1 · Cited by 17
Leukodystrophy or genetic leukoencephalopathy? Nature does not make leaps
Salsano, E. (2015) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2015.02.005 · Cited by 6
Tan, C., Wan, Y., Tan, M., Zhang, W., Wang, Z., Sun, F.-R., Miao, D., Tan, L., & Yu, J. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151073 · Cited by 6
“Similarly, using exome sequencing a study has revealed mutations in TREM2 in patients presenting as an FTD-like syndrome [14].”
Method[Splenic cyst. Review of the literature and report of 2 cases].
de Melo, V. A., Júnior, A. A., Andrade, L. C., Aragão, J. F. B., & Rosa, J. E. (1995) · PubMed · Cited by 6
The Role of Genetics in Alzheimer's Disease and Parkinson's Disease
Porter, T., Gozt, A., Mastaglia, F. L., & Laws, S. M. (2019) · Wiley eBooks · doi:10.1002/9781119356752.ch15 · Cited by 6
Soares, I. F. Z., Christofolini, D. M., Silva, L. G., Feder, D., & Carvalho, A. A. D. S. (2020) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1491 · Cited by 6
“In all patients, homozygous variants in the TREM2 gene were found, and none had a bone phenotype (Chouery et al., 2008; Giraldo et al., 2013; Guerreiro et al., 2013).”
BackgroundInfluentialβ-Catenin Pathway Is Involved in TREM2-Mediated Microglial Survival
Zulfiqar, S., & Tanriöver, G. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1087-17.2017 · Cited by 5
Williamson, J. C., & Larner, A. J. (2018) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000271 · Cited by 5
Ahmad, S. S., Younis, K., Jeandet, P., Aschner, M., & Khan, H. Z. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666210811160007 · Cited by 5
Wauters, E., Sleegers, K., Cruts, M., & Broeckhoven, C. V. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805120-7.00009-9 · Cited by 6
TREM2 R47H exacerbates immune response in Alzheimer’s disease brainPreprint
Korvatska, O., Kiianitsa, K., Ratushny, A., Matsushita, M., Beeman, N., Chien, W.-M., Satoh, J.-I., Dorschner, M., Keene, C., Bammler, T., et al. (2018) · bioRxiv · doi:10.1101/499319 · Cited by 4
“In PLOSL, homozygous inactivating mutations include premature stop codons (33, 34), splice site mutations (35, 36) and missense mutations D134G, K186N (4), Y38C, T66M, and V126G (37),(38),(5).”
BackgroundWhite matter hyperintensities and neurodegenerative dementias
Sassi, C. (2019) · Aging · doi:10.18632/aging.101967 · Cited by 4
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer’s diseasePreprint
Martiskainen, H., Willman, R.-M., Heikkinen, S., Müller, S. A., Sinisalo, R., Takalo, M., Mäkinen, P. M., Kuulasmaa, T., Pekkala, V., del Rey, A. G., et al. (2024) · medRxiv · doi:10.1101/2024.05.09.24307099 · Cited by 4
Alterations in the brain lipidome of Alzheimer's disease donors with rare TREM2 risk variants
Proitsi, P., Ebshiana, A., Wretlind, A., Xu, J., Hodges, A., & Legido‐Quigley, C. (2026) · Brain Communications · doi:10.1093/braincomms/fcaf452 · Cited by 3
Gilani, N., Bitarafan, F., Özaslan, M., Åsheim, S., Heidari, M., & Garshasbi, M. (2024) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.2476 · Cited by 3
Familial cerebral amyloid disorders with prominent white matter involvement
Banerjee, G., Schott, J. M., & Ryan, N. S. (2024) · Handbook of clinical neurology · doi:10.1016/b978-0-323-99209-1.00010-7 · Cited by 3
Origin and Development of Microglia
Patro, N., & Patro, I. K. (2022) · Springer eBooks · doi:10.1007/978-981-16-8313-8_7 · Cited by 3
Yuan, Q., Liu, X., Zhang, Y., Xian, Y., Zou, J., Zhang, X., Huang, P., Song, Y., & Lin, Z. (2021) · Molecules · doi:10.3390/molecules26092685 · Cited by 3
Network-Based Analysis for Uncovering Mechanisms Underlying Alzheimer’s Disease
Kikuchi, M., Ogishima, S., Mizuno, S., Miyashita, A., Kuwano, R., Nakaya, J., & Tanaka, H. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2627-5_29 · Cited by 3
Gorenjak, V., Arguinano, A.-A. A., Dadé, S., Stathopoulou, M., Vance, D. R., Masson, C., & Visvikis-Siest, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-25553-y · Cited by 3
Cell autonomous microglia defects in a stem cell model of frontotemporal dementiaPreprint
Iyer, A. K., Vermunt, L., Mirfakhar, F. S., Minaya, M., Acquarone, M., Koppisetti, R. K., Renganathan, A., You, S., Danhash, E., Verbeck, A. C., et al. (2024) · medRxiv · doi:10.1101/2024.05.15.24307444 · Cited by 3
Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease
Pillai, J. P., Sung, K., Shi, L. Z., & Wu, C. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.07.003 · Cited by 2
“Finally, the D86V caused significant damage to TREM2 as a charged residue was replaced with an uncharged and removal of hydrogen bond interactions [45].”
Microglial heterogeneity in neurological disorders: From dynamic states to druggable targets
Ou, Q., Dai, Z., Zhou, Y., Li, G., Liu, H., Li, J., He, C., Qin, S., & Su, Z. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.117994 · Cited by 3
Innate immune crosstalk in ALS/FTD pathogenesis
Shu, X., Yu, X., Xu, P., & Wang, A. (2026) · Cell Insight · doi:10.1016/j.cellin.2026.100340 · Cited by 2
“Moreover, TREM2 is a recognized risk gene in ALS/FTD (Cady et al., 2014; Guerreiro et al., 2013a); the TREM2 protein drives microglial survival, metabolic adaptation, and phagocytic activity, enabling the clearance of toxic aggregates such as poly-GA and TDP-43 (Shu et al., 2023; Xie et al., 2022).”
Revisiting TREM2: from multi-omics signaling networks to clinical translation
Yang, J., Wan, D., Ren, L., Lv, Y., & Zhao, H. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1782384 · Cited by 2
Genetics and Epigenetics in the Neurodegenerative Disorders of the Central Nervous System
Fenoglio, C. (2018) · Springer eBooks · doi:10.1007/978-3-319-72938-1_1 · Cited by 2
Reitz, C., & Tosto, G. (2013) · Journal of Molecular and Genetic Medicine · doi:10.4172/1747-0862.1000060 · Cited by 2
“Other homozygous TREM2 mutations have been described in patients presenting with frontotemporal-like dementia [53].”
BackgroundPosterior cortical atrophy: a single case cognitive and radiological follow-up
Esteves, S., Romero, D. A. R., Torralva, T., Cuitiño, M. M., Herndon, S., Couto, B., Ibáñez, A. M., Manes, F. F., & Roca, M. (2018) · Neurocase · doi:10.1080/13554794.2017.1421667 · Cited by 2
Metadata
- Authors
- Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., Emre, M., Singleton, A., & Hardy, J.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- JAMA Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2013-01-01
- Volume
- 70
- Issue
- 1
- Pages
- 78
- ISSN
- 2168-6149 (ISSN-L)
- PMC
- PMC4001789
- OpenAlex
- W1984557585
- Cited by
- 374
- References
- 27
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 20 · 2023: 17 · 2022: 12 · 2021: 39 · 2020: 34 · 2019: 22 · 2018: 32 · 2017: 37 · 2016: 29 · 2015: 40 · 2014: 26 · 2013: 21
- FWCI
- 27.37
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- JAMA Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (089698)
- National Institutes of Health
- National Institute on Aging (Z01AG000950)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- TREM2, frontotemporal dementia, homozygous mutation, genetic diagnosis, white matter abnormalities, behavior change, cognitive impairment, exome sequencing, Turkish patients
- MeSH terms
- Adult, Humans, Male, Membrane Glycoproteins, Mutation, Receptors, Immunologic, Risk Factors, Syndrome, Frontotemporal Dementia, Exome
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
