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1. Brain volumetric deficits in MAPT mutation carriers: a multisite study

Author

Chu, S.A. (Stephanie A.), Flagan, T.M. (Taru M.), Staffaroni, A.M. (Adam M.), Jiskoot, L.C. (Lize), Deng, J. (Jersey), Spina, S. (Salvatore), Zhang, L. (Liwen), Sturm, V.E. (Virginia E.), Yokoyama, J.S. (Jennifer S.), Seeley, W.W. (William W.), Papma, J.M. (Janne), Geschwind, H., Rosen, H.J. (Howard J.), Boeve, B.F. (Bradley F.), Boxer, A.L. (Adam), Heuer, H.W. (Hilary W.), Forsberg, L.K. (Leah K.), Brushaber, D.E. (Danielle E.), Grossman, M. (Murray), Coppola, G. (Giovanni), Dickerson, F. (Faith), Bordelon, Y.M. (Yvette M.), Faber, K. (Kelley), Feldman, H.H. (Howard), Fields, J.A. (Julie A.), Fong, J.C. (Jamie C.), Foroud, T. (Tatiana), Gavrilova, R.H. (Ralitza H.), Ghoshal, N. (Nupur), Graff-Radford, N.R. (Neill), Hsiung, G.Y.R. (Ging-Yuek), Huey, E.D. (Edward), Irwin, D.J. (David J.), Kantarci, K. (Kejal), Kaufer, D.I. (Daniel I.), Karydas, A.M. (Anna M.), Knopman, D.S. (David), Kornak, J. (John), Kramer, J.H. (Joel), Kukull, W.A., Lapid, M.I. (Maria I.), Litvan, I., Mackenzie, I.R.A. (Ian), Mendez, M.F. (Mario), Miller, B.L. (Bruce Lars), Onyike, C.U. (Chiadi), Pantelyat, A.Y. (Alexander Y.), Rademakers, S. (Suzanne), Marisa Ramos, E. (Eliana), Roberson, E.D. (Erik D.), Carmela Tartaglia, M. (Maria), Tatton, N.A. (Nadine A.), Toga, A.W. (Arthur), Vetor, A. (Ashley), Weintraub, S. (Sandra), Wong, B. (Bonnie), Wszolek, Z.K. (Zbigniew), Swieten, J.C. (John) van, Lee, S.E. (Suzee E.), Chu, S.A. (Stephanie A.), Flagan, T.M. (Taru M.), Staffaroni, A.M. (Adam M.), Jiskoot, L.C. (Lize), Deng, J. (Jersey), Spina, S. (Salvatore), Zhang, L. (Liwen), Sturm, V.E. (Virginia E.), Yokoyama, J.S. (Jennifer S.), Seeley, W.W. (William W.), Papma, J.M. (Janne), Geschwind, H., Rosen, H.J. (Howard J.), Boeve, B.F. (Bradley F.), Boxer, A.L. (Adam), Heuer, H.W. (Hilary W.), Forsberg, L.K. (Leah K.), Brushaber, D.E. (Danielle E.), Grossman, M. (Murray), Coppola, G. (Giovanni), Dickerson, F. (Faith), Bordelon, Y.M. (Yvette M.), Faber, K. (Kelley), Feldman, H.H. (Howard), Fields, J.A. (Julie A.), Fong, J.C. (Jamie C.), Foroud, T. (Tatiana), Gavrilova, R.H. (Ralitza H.), Ghoshal, N. (Nupur), Graff-Radford, N.R. (Neill), Hsiung, G.Y.R. (Ging-Yuek), Huey, E.D. (Edward), Irwin, D.J. (David J.), Kantarci, K. (Kejal), Kaufer, D.I. (Daniel I.), Karydas, A.M. (Anna M.), Knopman, D.S. (David), Kornak, J. (John), Kramer, J.H. (Joel), Kukull, W.A., Lapid, M.I. (Maria I.), Litvan, I., Mackenzie, I.R.A. (Ian), Mendez, M.F. (Mario), Miller, B.L. (Bruce Lars), Onyike, C.U. (Chiadi), Pantelyat, A.Y. (Alexander Y.), Rademakers, S. (Suzanne), Marisa Ramos, E. (Eliana), Roberson, E.D. (Erik D.), Carmela Tartaglia, M. (Maria), Tatton, N.A. (Nadine A.), Toga, A.W. (Arthur), Vetor, A. (Ashley), Weintraub, S. (Sandra), Wong, B. (Bonnie), Wszolek, Z.K. (Zbigniew), Swieten, J.C. (John) van, and Lee, S.E. (Suzee E.)

Abstract

Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes

Published
2020
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2. Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia

Author

Bonham, L.W. (Luke W.), Steele, N.Z.R. (Natasha Z. R.), Karch, C.M. (Celeste M.), Broce, I. (Iris), Geier, E.G. (Ethan G.), Wen, N.L. (Natalie L.), Momeni, P. (Parastoo), Hardy, J. (John), Miller, Z.A. (Zachary A.), Gorno-Tempini, M.L. (Maria Luisa), Hess, C.P. (Christopher P.), Lewis, P. (Patrick), Miller, B.L. (Bruce Lars), Seeley, W.W. (William W.), Manzoni, C. (Claudia), Desikan, R.S. (Rahul S.), Baranzini, S.E. (Sergio), Ferrari, R. (Raffaele), Yokoyama, J.S. (Jennifer S.), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Schofield, P.R. (P. R.), Halliday, G.M. (Glenda Margaret), Hodges, J. (John), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (E.), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (M.), Borroni, B. (Barbara), Padovani, A. (Alessandro), Cruchaga, C. (C.), Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (R.), Forloni, G. (Gianluigi), Albani, D. (D.), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (E.), Clarimón, J. (J.), Lleo, A. (Alberto), Blesa, R. (Rafael), Landqvist Waldö, M. (M.), Nilsson, K. (K.), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.Y.R. (Ging-Yuek), Mann, D.M.A. (D. M.A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.W. (Alan), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (M. C.), Pastor, P. (P.), Razquin, C. (Cristina), Ortega-Cubero, S. (S.), Alonso, E. (E.), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), St. George-Hyslop, P. (Peter), Rossi, G. (G.), Tagliavini, F. (F.), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (J.), Mead, S. (S.), Danek, A. (A.), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (J. Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (A.), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (J. E.), Hjermind, L.E. (Lena), Riemenschneider, M. (M.), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (W.), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H. (Huw), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (R. C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley), Parisi, J.E. (Joseph), Karydas, A.M. (A. M.), Rosen, H. (H.), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (H.), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, C. (Claudio), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (C.), Pasquier, F. (Florence), Rollin, A. (A.), Deramecourt, V. (Vincent), Lebouvier, T. (T.), Kapogiannis, D. (Dimitrios), Ferrucci, L. (L.), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Bonham, L.W. (Luke W.), Steele, N.Z.R. (Natasha Z. R.), Karch, C.M. (Celeste M.), Broce, I. (Iris), Geier, E.G. (Ethan G.), Wen, N.L. (Natalie L.), Momeni, P. (Parastoo), Hardy, J. (John), Miller, Z.A. (Zachary A.), Gorno-Tempini, M.L. (Maria Luisa), Hess, C.P. (Christopher P.), Lewis, P. (Patrick), Miller, B.L. (Bruce Lars), Seeley, W.W. (William W.), Manzoni, C. (Claudia), Desikan, R.S. (Rahul S.), Baranzini, S.E. (Sergio), Ferrari, R. (Raffaele), Yokoyama, J.S. (Jennifer S.), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Schofield, P.R. (P. R.), Halliday, G.M. (Glenda Margaret), Hodges, J. (John), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (E.), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (A.), Boada, M. (M.), Borroni, B. (Barbara), Padovani, A. (Alessandro), Cruchaga, C. (C.), Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (R.), Forloni, G. (Gianluigi), Albani, D. (D.), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (E.), Clarimón, J. (J.), Lleo, A. (Alberto), Blesa, R. (Rafael), Landqvist Waldö, M. (M.), Nilsson, K. (K.), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.Y.R. (Ging-Yuek), Mann, D.M.A. (D. M.A.), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.W. (Alan), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (M. C.), Pastor, P. (P.), Razquin, C. (Cristina), Ortega-Cubero, S. (S.), Alonso, E. (E.), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), St. George-Hyslop, P. (Peter), Rossi, G. (G.), Tagliavini, F. (F.), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (J.), Mead, S. (S.), Danek, A. (A.), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (J. Q.), Zee, J. (Jill) van der, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Leber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A. (A.), Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (J. E.), Hjermind, L.E. (Lena), Riemenschneider, M. (M.), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (W.), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H. (Huw), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (R. C.), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley), Parisi, J.E. (Joseph), Karydas, A.M. (A. M.), Rosen, H. (H.), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (H.), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, C. (Claudio), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, C. (C.), Pasquier, F. (Florence), Rollin, A. (A.), Deramecourt, V. (Vincent), Lebouvier, T. (T.), Kapogiannis, D. (Dimitrios), Ferrucci, L. (L.), Pickering-Brown, S. (Stuart), and Singleton, A. (Andrew)

Abstract

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism

Published
2019
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3. Frontotemporal dementia and its subtypes: A genome-wide association study

Author

Ferrari, R. (Roberto), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William), Schofield, C.J. (Christopher), Halliday, G.M. (Glenda Margaret), Hodges, J. (John), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (Agustin), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Cruchaga, C. (Carlos), Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimon, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.Y.R. (Ging-Yuek), Mann, D.M.A. (David), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.W. (Alan), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), St George-Hyslop, P.H. (Peter), Rossi, G. (Giulio) de, Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John), Zee, J. (Jill) van der, Deschamps, J. (Jacqueline), Langenhove, T. (Tim) van, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Le Ber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A., Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jorgen), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H. (Huw), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D.W. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley), Parisi, J.E. (Joseph), Seeley, W. (William), Miller, B.L. (Bruce Lars), Karydas, A. (Anna), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, C. (Claudio), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, M.J. (Maud J.L.), Pasquier, F. (Florence), Rollin, P.E. (Pierre), Deramecourt, V. (Vincent), Lebert, F. (Florence), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), Momeni, M. (Mona), Ferrari, R. (Roberto), Hernandez, D.G. (Dena), Nalls, M.A. (Michael), Rohrer, J.D. (Jonathan), Ramasamy, A. (Adaikalavan), Kwok, J.B.J. (John), Dobson-Stone, C. (Carol), Brooks, W.S. (William), Schofield, C.J. (Christopher), Halliday, G.M. (Glenda Margaret), Hodges, J. (John), Piguet, O. (Olivier), Bartley, L. (Lauren), Thompson, E. (Elizabeth), Haan, E. (Eric), Hernández, I. (Isabel), Ruiz, A. (Agustin), Boada, M. (Mercè), Borroni, B. (Barbara), Padovani, A. (Alessandro), Cruchaga, C. (Carlos), Cairns, N.J. (Nigel), Benussi, L. (Luisa), Binetti, G. (Giuliano), Ghidoni, R. (Roberta), Forloni, G. (Gianluigi), Galimberti, D. (Daniela), Fenoglio, C. (Chiara), Serpente, M. (Maria), Scarpini, E. (Elio), Clarimon, J. (Jordi), Lleo, A. (Alberto), Blesa, R. (Rafael), Waldö, M.L. (Maria Landqvist), Nilsson, K. (Karin), Nilsson, C. (Christer), Mackenzie, I.R.A. (Ian), Hsiung, G.Y.R. (Ging-Yuek), Mann, D.M.A. (David), Grafman, J. (Jordan), Morris, C.M. (Chris), Attems, J. (Johannes), Griffiths, T.D. (Timothy), McKeith, I.G. (Ian), Thomas, A.W. (Alan), Pietrini, P. (P.), Huey, E.D. (Edward), Wassermann, E.M. (Eric), Baborie, A. (Atik), Jaros, J.A.J. (Julian), Tierney, M.C. (Michael), Pastor, P. (Pau), Razquin, C. (Cristina), Ortega-Cubero, S. (Sara), Alonso, E. (Elena), Perneczky, R. (Robert), Diehl-Schmid, J. (Janine), Alexopoulos, E.C. (Evangelos), Kurz, A., Rainero, I. (Innocenzo), Rubino, M. (Maurizio), Pinessi, L. (Lorenzo), Rogaeva, E. (Ekaterina), St George-Hyslop, P.H. (Peter), Rossi, G. (Giulio) de, Tagliavini, F. (Fabrizio), Giaccone, G. (Giuseppe), Rowe, J.B. (James), Schlachetzki, J.C.M. (Johannes C.), Uphill, J. (James), Collinge, J. (John), Mead, S. (Simon), Danek, A. (Adrian), Deerlin, V.M. (Vivianna), Grossman, M. (Murray), Trojanowski, J.Q. (John), Zee, J. (Jill) van der, Deschamps, J. (Jacqueline), Langenhove, T. (Tim) van, Cruts, M. (Marc), Broeckhoven, C. (Christine) van, Cappa, S.F. (Stefano), Le Ber, I. (Isabelle), Hannequin, D. (Didier), Golfier, V. (Véronique), Vercelletto, M. (Martine), Brice, A., Nacmias, B. (Benedetta), Sorbi, S. (Sandro), Bagnoli, S. (Silvia), Piaceri, I. (Irene), Nielsen, J.E. (Jorgen), Hjermind, L.E. (Lena), Riemenschneider, M. (Matthias), Mayhaus, M. (Manuel), Ibach, B. (Bernd), Gasparoni, G. (Gilles), Pichler, I. (Irene), Gu, W. (Wei), Rossor, M. (Martin), Fox, N.C. (Nick), Warren, J.D. (Jason), Spillantini, M.G., Morris, H. (Huw), Rizzu, P. (Patrizia), Heutink, P. (Peter), Snowden, J. (Julie), Rollinson, S. (Sara), Richardson, A. (Anna), Gerhard, A. (Alex), Bruni, A.C. (Amalia), Maletta, R. (Raffaele), Frangipane, F. (Francesca), Cupidi, C. (Chiara), Bernardi, L. (Livia), Anfossi, M. (Maria), Gallo, V. (Valentina), Conidi, A. (Andrea), Smirne, N. (Nicoletta), Rademakers, S. (Suzanne), Baker, M.C. (Matthew), Dickson, D.W. (Dennis), Graff-Radford, N.R. (Neill), Petersen, R.C. (Ronald), Knopman, D.S. (David), Josephs, K.A. (Keith), Boeve, B.F. (Bradley), Parisi, J.E. (Joseph), Seeley, W. (William), Miller, B.L. (Bruce Lars), Karydas, A. (Anna), Rosen, H. (Howard), Swieten, J.C. (John) van, Dopper, E.G.P. (Elise), Seelaar, H. (Harro), Pijnenburg, Y.A.L. (Yolande), Scheltens, P. (Philip), Logroscino, G. (Giancarlo), Capozzo, R. (Rosa), Novelli, V. (Valeria), Puca, A.A. (Annibale), Franceschi, C. (Claudio), Postiglione, A. (Alfredo), Milan, D.J. (David), Sorrentino, D. (Dario), Kristiansen, M. (Mark), Chiang, Y.T., Graff, M.J. (Maud J.L.), Pasquier, F. (Florence), Rollin, P.E. (Pierre), Deramecourt, V. (Vincent), Lebert, F. (Florence), Kapogiannis, D. (Dimitrios), Ferrucci, L. (Luigi), Pickering-Brown, S. (Stuart), Singleton, A. (Andrew), Hardy, J. (John), and Momeni, M. (Mona)

Abstract

Background: Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods: We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 h

Published
2014
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