Frontotemporal dementia and its subtypes: a genome-wide association study
Por:
Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Brooks, WS, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernandez, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimon, J, Lleo, A, Blesa, R, Waldo, ML, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, GYR, Mann, DMA, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, McKeith, IG, Thomas, AJ, Pietrini, P, Huey, ED, Wassermann, EM, Baborie, A, Jaros, E, Tierney, MC, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, JB, Schlachetzki, JCM, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, VM, Grossman, M, Trojanowski, JQ, van der Zee, J, Deschamps, W, Van Langenhove, T, Cruts, M, Van Broeckhoven, C, Cappa, SF, Le Ber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, JE, Hjermind, LE, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, MN, Fox, NC, Warren, JD, Spillantini, MG, Morris, HR, Rizzu, P, Heutink, P, Snowden, JS, Rollinson, S, Richardson, A, Gerhard, A, Bruni, AC, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, ME, Smirne, N, Rademakers, R, Baker, M, Dickson, DW, Graff-Radford, NR, Petersen, RC, Knopman, D, Josephs, KA, Boeve, BF, Parisi, JE, Seeley, WW, Miller, BL, Karydas, AM, Rosen, H, van Swieten, JC, Dopper, EGP, Seelaar, H, Al Pijnenburg, Y, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, AA, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, HH, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebert, F, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, AB, Hardy, J, Momeni, P
Publicada:
1 jul 2014
Resumen:
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 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 x 10(-8)) single-nucleotide polymorphisms.
Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 x 10-8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1.05 x 10(-8); odds ratio=1.204 [95% CI 1.11-1.30]), rs9268856 (p=5.51 x 10(-9); 0.809 [0.76-0.86]) and rs1980493 (p value=1.57 x 10(-8), 0.775 [0.69-0-86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2.44 x 10(-7); 0.814 [0.71-0.92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis.
Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD.
Filiaciones:
Ferrari, R:
Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, Lubbock, TX 79430 USA
UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England
Hernandez, DG:
UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Nalls, MA:
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Rohrer, JD:
UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England
UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London WC1N 3BG, England
Ramasamy, A:
UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England
Kings Coll London, Guys Hosp, Dept Med & Mol Genet, London WC2R 2LS, England
Kwok, JBJ:
Univ New S Wales, Sydney, NSW, Australia
Dobson-Stone, C:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New S Wales, Sydney, NSW, Australia
Brooks, WS:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New S Wales, Sydney, NSW, Australia
Schofield, PR:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New S Wales, Sydney, NSW, Australia
Halliday, GM:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New S Wales, Sydney, NSW, Australia
Hodges, JR:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New S Wales, Sydney, NSW, Australia
Piguet, O:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New S Wales, Sydney, NSW, Australia
Bartley, L:
Neurosci Res Australia, Sydney, NSW, Australia
Thompson, E:
Womens & Childrens Hosp, SA Pathol, South Australian Clin Genet Serv, Adelaide, SA, Australia
Haan, E:
Womens & Childrens Hosp, SA Pathol, South Australian Clin Genet Serv, Adelaide, SA, Australia
Univ Adelaide, Dept Paediat, Adelaide, SA, Australia
Hernandez, I:
Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain
Ruiz, A:
Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain
Boada, M:
Inst Catala Neurociencies Aplicades, Memory Clin Fundacio ACE, Barcelona, Spain
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Inst Recerca, E-08193 Barcelona, Spain
Borroni, B:
Univ Brescia, Neurol Clin, Brescia, Italy
Padovani, A:
Univ Brescia, Neurol Clin, Brescia, Italy
Cruchaga, C:
Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
Washington Univ, Sch Med, Hope Ctr, St Louis, MO USA
Cairns, NJ:
Washington Univ, Sch Med, Hope Ctr, St Louis, MO USA
Washington Univ, Dept Pathol & Immunol, St Louis, MO USA
Benussi, L:
IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, NeuroBioGen Lab, Memory Clin, Brescia, Italy
Binetti, G:
IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, NeuroBioGen Lab, Memory Clin, Brescia, Italy
Ghidoni, R:
IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Prote Unit, Brescia, Italy
Forloni, G:
IRCCS Ist Ric Farmacol Mario Negri, Milan, Italy
Galimberti, D:
Univ Milan, Milan, Italy
IRCCS Osped Maggiore Policlin, Fdn Ca Granda, Milan, Italy
Fenoglio, C:
Univ Milan, Milan, Italy
IRCCS Osped Maggiore Policlin, Fdn Ca Granda, Milan, Italy
Serpente, M:
Univ Milan, Milan, Italy
IRCCS Osped Maggiore Policlin, Fdn Ca Granda, Milan, Italy
Scarpini, E:
Univ Milan, Milan, Italy
IRCCS Osped Maggiore Policlin, Fdn Ca Granda, Milan, Italy
Clarimon, J:
Univ Autonoma Barcelona, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, St Pau Biomed Res Inst, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Lleo, A:
Univ Autonoma Barcelona, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, St Pau Biomed Res Inst, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Blesa, R:
Univ Autonoma Barcelona, Memory Unit, Dept Neurol, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, St Pau Biomed Res Inst, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Waldo, ML:
Lund Univ, Unit Geriatr Psychiat, Dept Clin Sci, Lund, Sweden
Nilsson, K:
Lund Univ, Unit Geriatr Psychiat, Dept Clin Sci, Lund, Sweden
Nilsson, C:
Lund Univ, Clin Memory Res Unit, Dept Clin Sci, Lund, Sweden
Mackenzie, IRA:
Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada
Hsiung, GYR:
Univ British Columbia, Div Neurol, Vancouver, BC V5Z 1M9, Canada
Mann, DMA:
Univ Manchester, Salford Royal Hosp, Inst Brain Behav & Mental Hlth, Salford, Lancs, England
Grafman, J:
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Phys Med, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Rehabil Psychiat & Cognit Neurol, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Ctr, Evanston, IL 60208 USA
Northwestern Univ, Weinberg Coll Arts & Sci, Dept Psychol, Evanston, IL 60208 USA
Morris, CM:
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Phys Med, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Rehabil Psychiat & Cognit Neurol, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Ctr, Evanston, IL 60208 USA
Newcastle Univ, Newcastle Brain Tissue Resource, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Attems, J:
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Phys Med, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Rehabil Psychiat & Cognit Neurol, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Ctr, Evanston, IL 60208 USA
Newcastle Univ, Newcastle Brain Tissue Resource, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Griffiths, TD:
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Phys Med, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Rehabil Inst Chicago, Dept Rehabil Psychiat & Cognit Neurol, Evanston, IL 60208 USA
Northwestern Univ, Feinberg Sch Med, Alzheimers Dis Ctr, Evanston, IL 60208 USA
Newcastle Univ, Newcastle Brain Tissue Resource, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
McKeith, IG:
Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Thomas, AJ:
Univ Adelaide, Dept Paediat, Adelaide, SA, Australia
Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Pietrini, P:
Pisa Univ Hosp, Psychol Branch, Pisa, Italy
Univ Pisa, Lab Clin Biochem & Mol Biol, Pisa, Italy
Huey, ED:
Columbia Univ, Taub Inst, Dept Psychiat, New York, NY 10032 USA
Columbia Univ, Taub Inst, Dept Neurol, New York, NY 10032 USA
Wassermann, EM:
NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA
Baborie, A:
Walton Ctr FT, Dept Neuropathol, Liverpool, Merseyside, England
Jaros, E:
Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
Royal Victoria Infirm, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England
Tierney, MC:
NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA
Pastor, P:
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain
Univ Navarra, Sch Med, Dept Neurol, Univ Navarra Clin, E-31080 Pamplona, Spain
Razquin, C:
Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain
Ortega-Cubero, S:
Ctr Networker Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain
Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain
Alonso, E:
Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain
Perneczky, R:
Univ London Imperial Coll Sci Technol & Med, Neuroepidemiol & Ageing Res Unit, Sch Publ Hlth, Fac Med, London, England
West London Mental Hlth Trust, West London Cognit Disorders Treatment & Res Unit, London TW8 8DS, England
Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany
Diehl-Schmid, J:
Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany
Alexopoulos, P:
Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany
Kurz, A:
Tech Univ Munich, Dept Psychiat & Psychotherapy, D-80290 Munich, Germany
Rainero, I:
Univ Turin, Dept Neurosci, I-10124 Turin, Italy
AO Citta Salute & Sci Torino, Turin, Italy
Rubino, E:
AO Citta Salute & Sci Torino, Turin, Italy
Pinessi, L:
AO Citta Salute & Sci Torino, Turin, Italy
Rogaeva, E:
Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada
St George-Hyslop, P:
Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada
Univ Toronto, Dept Med, Toronto, ON, Canada
Univ Cambridge, Cambridge Inst Med Res, Cambridge, England
Univ Cambridge, Dept Clin Neurosci, Cambridge, England
Rossi, G:
Fdn IRCCS Ist Neurol Carlo Besta, Div Neurol & Neuropathol 5, Milan, Italy
Tagliavini, F:
Fdn IRCCS Ist Neurol Carlo Besta, Div Neurol & Neuropathol 5, Milan, Italy
Giaccone, G:
Fdn IRCCS Ist Neurol Carlo Besta, Div Neurol & Neuropathol 5, Milan, Italy
Rowe, JB:
Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0SZ, England
MRC, Cognit & Brain Sci Unit, Cambridge, England
Schlachetzki, JCM:
Univ Freiburg, Dept Psychiat & Psychotherapy, Freiburg, Germany
Univ Hosp Erlangen, Dept Mol Neurol, Erlangen, Germany
Uphill, J:
UCL, Inst Neurol, Dept Neurodegenerat Dis, MRC,Prion Unit, London WC1N 3BG, England
Collinge, J:
UCL, Inst Neurol, Dept Neurodegenerat Dis, MRC,Prion Unit, London WC1N 3BG, England
Mead, S:
UCL, Inst Neurol, Dept Neurodegenerat Dis, MRC,Prion Unit, London WC1N 3BG, England
Danek, A:
Univ Munich, Neurol Klin & Poliklin, Munich, Germany
German Ctr Neurodegenerat Dis, Munich, Germany
Van Deerlin, VM:
Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA
Penn Frontotemporal Degenerat Ctr, Philadelphia, PA USA
Grossman, M:
Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA
Penn Frontotemporal Degenerat Ctr, Philadelphia, PA USA
Trojanowski, JQ:
Univ Penn, Perelman Sch Med, Dept Neurol, Philadelphia, PA 19104 USA
Penn Frontotemporal Degenerat Ctr, Philadelphia, PA USA
van der Zee, J:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Deschamps, W:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Van Langenhove, T:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Cruts, M:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Van Broeckhoven, C:
VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium
Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium
Cappa, SF:
Univ Vita Salute San Raffaele, Dept Clin Neurosci, Neurorehabil Unit, Milan, Italy
Ist Sci San Raffaele, I-20132 Milan, Italy
Le Ber, I:
Univ Paris 06, INSERM, UMR S975, CRICM, F-75013 Paris, France
Univ Paris 06, UMR S975, F-75013 Paris, France
CNRS, UMR 7223, F-75013 Paris, France
Hop La Pitie Salpetriere, AP HP, Dept Neurol, Ctr References Demences Bares, F-75013 Paris, France
Hannequin, D:
Rouen Univ Hosp, Serv Neurol, INSERM, U1079,CNR MAJ, Rouen, France
Golfier, V:
CH St Brieuc, Serv Neurol, St Brieuc, France
Vercelletto, M:
CHU Nantes, Serv Neurol, Nantes, France
Brice, A:
Univ Paris 06, INSERM, UMR S975, CRICM, F-75013 Paris, France
Univ Paris 06, UMR S975, F-75013 Paris, France
CNRS, UMR 7223, F-75013 Paris, France
Hop La Pitie Salpetriere, AP HP, Dept Neurol, Ctr References Demences Bares, F-75013 Paris, France
Nacmias, B:
Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy
Sorbi, S:
Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy
Bagnoli, S:
Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy
Piaceri, I:
Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy
Nielsen, JE:
Copenhagen Univ Hosp, Dept Neurol, Rigshosp, Danish Dementia Res Ctr,Neurogenet Clin, Copenhagen, Denmark
Univ Copenhagen, Panum Inst, Neurogenet Sect, Dept Cellular & Mol Med, DK-1168 Copenhagen, Denmark
Hjermind, LE:
Copenhagen Univ Hosp, Dept Neurol, Rigshosp, Danish Dementia Res Ctr,Neurogenet Clin, Copenhagen, Denmark
Univ Copenhagen, Panum Inst, Neurogenet Sect, Dept Cellular & Mol Med, DK-1168 Copenhagen, Denmark
Riemenschneider, M:
Saarland Univ Hosp, Dept Psychiat & Psychotherapy, Homburg, Germany
Univ Saarland, Neurogenet Lab, Homburg, Germany
Mayhaus, M:
Univ Saarland, Neurogenet Lab, Homburg, Germany
Ibach, B:
Univ Regensburg, Dept Psychiat Psychotherapy Psychosomat, D-93053 Regensburg, Germany
Gasparoni, G:
Univ Saarland, Neurogenet Lab, Homburg, Germany
Pichler, S:
Univ Saarland, Neurogenet Lab, Homburg, Germany
Gu, W:
Univ Saarland, Neurogenet Lab, Homburg, Germany
Univ Luxembourg, Luxembourg Ctr Syst Biomed, Luxembourg, Luxembourg
Rossor, MN:
UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London WC1N 3BG, England
Fox, NC:
UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London WC1N 3BG, England
Warren, JD:
UCL, Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London WC1N 3BG, England
Spillantini, MG:
Univ Cambridge, Dept Clin Neurosci, John van Geest Brain Repair Ctr, Cambridge, England
Morris, HR:
Cardiff Univ, Sch Med, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales
Rizzu, P:
German Ctr Neurodegenerat Dis Tubingen, Tubingen, Germany
Heutink, P:
German Ctr Neurodegenerat Dis Tubingen, Tubingen, Germany
Snowden, JS:
Univ Manchester, Fac Med & Human Sci, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England
Rollinson, S:
Univ Manchester, Fac Med & Human Sci, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England
Richardson, A:
Univ Manchester, Fac Med & Human Sci, Salford Royal Fdn Trust, Manchester M13 9PL, Lancs, England
Gerhard, A:
Univ Manchester, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England
Bruni, AC:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Maletta, R:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Frangipane, F:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Cupidi, C:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Bernardi, L:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Anfossi, M:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Gallo, M:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Conidi, ME:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Smirne, N:
ASPCZ, Reg Neurogenet Ctr, Lamezia Terme, Italy
Rademakers, R:
Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
Baker, M:
Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
Dickson, DW:
Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
Graff-Radford, NR:
Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA
Petersen, RC:
Mayo Clin, Dept Neurol, Rochester, MN USA
Knopman, D:
Mayo Clin, Dept Neurol, Rochester, MN USA
Josephs, KA:
Mayo Clin, Dept Neurol, Rochester, MN USA
Boeve, BF:
Mayo Clin, Dept Neurol, Rochester, MN USA
Parisi, JE:
Mayo Clin, Dept Pathol, Rochester, MN USA
Seeley, WW:
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
Miller, BL:
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
Karydas, AM:
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
Rosen, H:
Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA
van Swieten, JC:
Erasmus MC, Dept Neurol, Rotterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Med Genet, Amsterdam, Netherlands
Dopper, EGP:
Erasmus MC, Dept Neurol, Rotterdam, Netherlands
Seelaar, H:
Erasmus MC, Dept Neurol, Rotterdam, Netherlands
Al Pijnenburg, Y:
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands
Scheltens, P:
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands
Logroscino, G:
Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs Aldo M, I-70121 Bari, Italy
Capozzo, R:
Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs Aldo M, I-70121 Bari, Italy
Novelli, V:
IRCCS Fdn S Maugeri, Dept Mol Cardiol, Pavia, Italy
Puca, AA:
IRCCS Multimed, Cardiovasc Res Unit, Milan, Italy
Univ Salerno, Dept Med & Surg, I-84081 Baronissi, SA, Italy
Franceschi, M:
IRCCS Multimed, Dept Neurol, Milan, Italy
Postiglione, A:
Univ Naples Federico II, Dept Clin Med & Surg, Naples, Italy
Milan, G:
Geriatr Ctr Frullone ASL Napoli 1 Ctr, Naples, Italy
Sorrentino, P:
Geriatr Ctr Frullone ASL Napoli 1 Ctr, Naples, Italy
Kristiansen, M:
UCL, Inst Child Hlth, London WC1N 3BG, England
Chiang, HH:
Karolinska Inst, Dept NVS, KI Alzheimer Dis Res Ctr, Stockholm, Sweden
Karolinska Univ Hosp, Genet Unit, Dept Geriatr Med, Stockholm, Sweden
Graff, C:
Karolinska Inst, Dept NVS, KI Alzheimer Dis Res Ctr, Stockholm, Sweden
Karolinska Univ Hosp, Genet Unit, Dept Geriatr Med, Stockholm, Sweden
Pasquier, F:
Univ Lille Nord France, Lille, France
Rollin, A:
Univ Lille Nord France, Lille, France
Deramecourt, V:
Univ Lille Nord France, Lille, France
Lebert, F:
Univ Lille Nord France, Lille, France
Kapogiannis, D:
NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA
Ferrucci, L:
NIA, Clin Res Branch, Bethesda, MD 20892 USA
Pickering-Brown, S:
Univ Manchester, Fac Med & Human Sci, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England
Singleton, AB:
NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
Hardy, J:
UCL, Inst Neurol, Reta Lila Weston Res Labs, Dept Mol Neurosci, London WC1N 3BG, England
Momeni, P:
Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, Lubbock, TX 79430 USA
Green Accepted, Green Submitted
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