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Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes

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Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes. / Thelen, Mathias; Razquin, Cristina; Hernández, Isabel; Gorostidi, Ana; Sánchez-Valle, Raquel; Ortega-Cubero, Sara; Wolfsgruber, Steffen; Drichel, Dmitriy; Fliessbach, Klaus; Duenkel, Tanja; Damian, Marinella; Heilmann, Stefanie; Slotosch, Anja; Lennarz, Martina; Seijo-Martínez, Manuel; Rene, Ramón; Kornhuber, Johannes; Peters, Oliver; Luckhaus, Christian; Jahn, Holger; Hüll, Michael; Rüther, Eckart; Wiltfang, Jens; Lorenzo, Elena; Gascon, Jordi; Lleó, Alberto; Lladó, Albert; Campdelacreu, Jaume; Moreno, Fermin; Ahmadzadehfar, Hojjat; Fortea, Juan; Indakoetxea, Begoña; Heneka, Michael T; Wetter, Axel; Pastor, Maria A; Riverol, Mario; Becker, Tim; Frölich, Lutz; Tárraga, Lluís; Boada, Mercè; Wagner, Michael; Jessen, Frank; Maier, Wolfgang; Clarimón, Jordi; López de Munain, Adolfo; Ruiz, Agustín; Pastor, Pau; Ramirez, Alfredo; Dementia Genetics Spanish Consortium (DEGESCO).

In: NEUROBIOL AGING, Vol. 35, No. 11, 01.11.2014, p. 2657.e13-9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Thelen, M, Razquin, C, Hernández, I, Gorostidi, A, Sánchez-Valle, R, Ortega-Cubero, S, Wolfsgruber, S, Drichel, D, Fliessbach, K, Duenkel, T, Damian, M, Heilmann, S, Slotosch, A, Lennarz, M, Seijo-Martínez, M, Rene, R, Kornhuber, J, Peters, O, Luckhaus, C, Jahn, H, Hüll, M, Rüther, E, Wiltfang, J, Lorenzo, E, Gascon, J, Lleó, A, Lladó, A, Campdelacreu, J, Moreno, F, Ahmadzadehfar, H, Fortea, J, Indakoetxea, B, Heneka, MT, Wetter, A, Pastor, MA, Riverol, M, Becker, T, Frölich, L, Tárraga, L, Boada, M, Wagner, M, Jessen, F, Maier, W, Clarimón, J, López de Munain, A, Ruiz, A, Pastor, P, Ramirez, A & Dementia Genetics Spanish Consortium (DEGESCO) 2014, 'Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes', NEUROBIOL AGING, vol. 35, no. 11, pp. 2657.e13-9. https://doi.org/10.1016/j.neurobiolaging.2014.06.018

APA

Thelen, M., Razquin, C., Hernández, I., Gorostidi, A., Sánchez-Valle, R., Ortega-Cubero, S., Wolfsgruber, S., Drichel, D., Fliessbach, K., Duenkel, T., Damian, M., Heilmann, S., Slotosch, A., Lennarz, M., Seijo-Martínez, M., Rene, R., Kornhuber, J., Peters, O., Luckhaus, C., ... Dementia Genetics Spanish Consortium (DEGESCO) (2014). Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes. NEUROBIOL AGING, 35(11), 2657.e13-9. https://doi.org/10.1016/j.neurobiolaging.2014.06.018

Vancouver

Thelen M, Razquin C, Hernández I, Gorostidi A, Sánchez-Valle R, Ortega-Cubero S et al. Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes. NEUROBIOL AGING. 2014 Nov 1;35(11):2657.e13-9. https://doi.org/10.1016/j.neurobiolaging.2014.06.018

Bibtex

@article{a750e6fcb8824f4785845906a649e966,
title = "Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes",
abstract = "Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.",
author = "Mathias Thelen and Cristina Razquin and Isabel Hern{\'a}ndez and Ana Gorostidi and Raquel S{\'a}nchez-Valle and Sara Ortega-Cubero and Steffen Wolfsgruber and Dmitriy Drichel and Klaus Fliessbach and Tanja Duenkel and Marinella Damian and Stefanie Heilmann and Anja Slotosch and Martina Lennarz and Manuel Seijo-Mart{\'i}nez and Ram{\'o}n Rene and Johannes Kornhuber and Oliver Peters and Christian Luckhaus and Holger Jahn and Michael H{\"u}ll and Eckart R{\"u}ther and Jens Wiltfang and Elena Lorenzo and Jordi Gascon and Alberto Lle{\'o} and Albert Llad{\'o} and Jaume Campdelacreu and Fermin Moreno and Hojjat Ahmadzadehfar and Juan Fortea and Bego{\~n}a Indakoetxea and Heneka, {Michael T} and Axel Wetter and Pastor, {Maria A} and Mario Riverol and Tim Becker and Lutz Fr{\"o}lich and Llu{\'i}s T{\'a}rraga and Merc{\`e} Boada and Michael Wagner and Frank Jessen and Wolfgang Maier and Jordi Clarim{\'o}n and {L{\'o}pez de Munain}, Adolfo and Agust{\'i}n Ruiz and Pau Pastor and Alfredo Ramirez and {Dementia Genetics Spanish Consortium (DEGESCO)}",
note = "Copyright {\textcopyright} 2014 Elsevier Inc. All rights reserved.",
year = "2014",
month = nov,
day = "1",
doi = "10.1016/j.neurobiolaging.2014.06.018",
language = "English",
volume = "35",
pages = "2657.e13--9",
journal = "NEUROBIOL AGING",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Investigation of the role of rare TREM2 variants in frontotemporal dementia subtypes

AU - Thelen, Mathias

AU - Razquin, Cristina

AU - Hernández, Isabel

AU - Gorostidi, Ana

AU - Sánchez-Valle, Raquel

AU - Ortega-Cubero, Sara

AU - Wolfsgruber, Steffen

AU - Drichel, Dmitriy

AU - Fliessbach, Klaus

AU - Duenkel, Tanja

AU - Damian, Marinella

AU - Heilmann, Stefanie

AU - Slotosch, Anja

AU - Lennarz, Martina

AU - Seijo-Martínez, Manuel

AU - Rene, Ramón

AU - Kornhuber, Johannes

AU - Peters, Oliver

AU - Luckhaus, Christian

AU - Jahn, Holger

AU - Hüll, Michael

AU - Rüther, Eckart

AU - Wiltfang, Jens

AU - Lorenzo, Elena

AU - Gascon, Jordi

AU - Lleó, Alberto

AU - Lladó, Albert

AU - Campdelacreu, Jaume

AU - Moreno, Fermin

AU - Ahmadzadehfar, Hojjat

AU - Fortea, Juan

AU - Indakoetxea, Begoña

AU - Heneka, Michael T

AU - Wetter, Axel

AU - Pastor, Maria A

AU - Riverol, Mario

AU - Becker, Tim

AU - Frölich, Lutz

AU - Tárraga, Lluís

AU - Boada, Mercè

AU - Wagner, Michael

AU - Jessen, Frank

AU - Maier, Wolfgang

AU - Clarimón, Jordi

AU - López de Munain, Adolfo

AU - Ruiz, Agustín

AU - Pastor, Pau

AU - Ramirez, Alfredo

AU - Dementia Genetics Spanish Consortium (DEGESCO)

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.

AB - Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17-14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.

U2 - 10.1016/j.neurobiolaging.2014.06.018

DO - 10.1016/j.neurobiolaging.2014.06.018

M3 - SCORING: Journal article

C2 - 25042114

VL - 35

SP - 2657.e13-9

JO - NEUROBIOL AGING

JF - NEUROBIOL AGING

SN - 0197-4580

IS - 11

ER -