Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

Celia Kun-Rodrigues; Owen A. Ross; Tatiana Orme; Claire Shepherd; Laura Parkkinen; Lee Darwent; Dena Hernandez; Olaf Ansorge; Lorraine N. Clark; Lawrence S. Honig; Karen Marder; Afina Lemstra; Philippe Scheltens; Wiesje van der Flier; Eva Louwersheimer; Henne Holstege; Ekaterina Rogaeva; Peter St. George-Hyslop; Elisabet Londos; Henrik Zetterberg; Imelda Barber; Anne Braae; Kristelle Brown; Kevin Morgan; Walter Maetzler; Daniela Berg; Claire Troakes; Safa Al-Sarraj; Tammaryn Lashley; Janice Holton; Yaroslau Compta; Vivianna Van Deerlin; John Q. Trojanowski; Geidy E. Serrano; Thomas G. Beach; Jordi Clarimon; Alberto Lleó; Estrella Morenas-Rodríguez; Suzanne Lesage; Douglas Galasko; Eliezer Masliah; Isabel Santana; Monica Diez; Pau Pastor; Pentti J. Tienari; Liisa Myllykangas; Minna Oinas; Tamas Revesz; Andrew Lees; Brad F. Boeve; Ronald C. Petersen; Tanis J. Ferman; Valentina Escott-Price; Neill Graff-Radford; Nigel J. Cairns; John C. Morris; David J. Stone; Stuart Pickering-Brown; David Mann; Dennis W. Dickson; Glenda M. Halliday; Andrew Singleton; Rita Guerreiro; Jose Bras

doi:10.1016/j.neurobiolaging.2016.08.023

Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

Celia Kun-Rodrigues, Owen A. Ross, Tatiana Orme, Claire Shepherd, Laura Parkkinen, Lee Darwent, Dena Hernandez, Olaf Ansorge, Lorraine N. Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Philippe Scheltens, Wiesje van der Flier, Eva Louwersheimer, Henne Holstege, Ekaterina Rogaeva, Peter St. George-Hyslop, Elisabet Londos, Henrik ZetterbergImelda Barber, Anne Braae, Kristelle Brown, Kevin Morgan, Walter Maetzler, Daniela Berg, Claire Troakes, Safa Al-Sarraj, Tammaryn Lashley, Janice Holton, Yaroslau Compta, Vivianna Van Deerlin, John Q. Trojanowski, Geidy E. Serrano, Thomas G. Beach, Jordi Clarimon, Alberto Lleó, Estrella Morenas-Rodríguez, Suzanne Lesage, Douglas Galasko, Eliezer Masliah, Isabel Santana, Monica Diez, Pau Pastor, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Tamas Revesz, Andrew Lees, Brad F. Boeve, Ronald C. Petersen, Tanis J. Ferman, Valentina Escott-Price, Neill Graff-Radford, Nigel J. Cairns, John C. Morris, David J. Stone, Stuart Pickering-Brown, David Mann, Dennis W. Dickson, Glenda M. Halliday, Andrew Singleton, Rita Guerreiro, Jose Bras

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Abstract

C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB.

Original language	English (US)
Pages (from-to)	214.e13-214.e15
Journal	Neurobiology of aging
Volume	49
DOIs	https://doi.org/10.1016/j.neurobiolaging.2016.08.023
State	Published - Jan 1 2017

Keywords

C9orf72
Dementia with Lewy bodies (DLB)
Genetic screen

ASJC Scopus subject areas

Neuroscience(all)
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2016.08.023

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Kun-Rodrigues, C., Ross, O. A., Orme, T., Shepherd, C., Parkkinen, L., Darwent, L., Hernandez, D., Ansorge, O., Clark, L. N., Honig, L. S., Marder, K., Lemstra, A., Scheltens, P., van der Flier, W., Louwersheimer, E., Holstege, H., Rogaeva, E., St. George-Hyslop, P., Londos, E., ... Bras, J. (2017). Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies. Neurobiology of aging, 49, 214.e13-214.e15. https://doi.org/10.1016/j.neurobiolaging.2016.08.023

Kun-Rodrigues, C, Ross, OA, Orme, T, Shepherd, C, Parkkinen, L, Darwent, L, Hernandez, D, Ansorge, O, Clark, LN, Honig, LS, Marder, K, Lemstra, A, Scheltens, P, van der Flier, W, Louwersheimer, E, Holstege, H, Rogaeva, E, St. George-Hyslop, P, Londos, E, Zetterberg, H, Barber, I, Braae, A, Brown, K, Morgan, K, Maetzler, W, Berg, D, Troakes, C, Al-Sarraj, S, Lashley, T, Holton, J, Compta, Y, Van Deerlin, V, Trojanowski, JQ, Serrano, GE, Beach, TG, Clarimon, J, Lleó, A, Morenas-Rodríguez, E, Lesage, S, Galasko, D, Masliah, E, Santana, I, Diez, M, Pastor, P, Tienari, PJ, Myllykangas, L, Oinas, M, Revesz, T, Lees, A, Boeve, BF , Petersen, RC , Ferman, TJ, Escott-Price, V, Graff-Radford, N, Cairns, NJ, Morris, JC, Stone, DJ, Pickering-Brown, S, Mann, D, Dickson, DW, Halliday, GM, Singleton, A, Guerreiro, R & Bras, J 2017, 'Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies', Neurobiology of aging, vol. 49, pp. 214.e13-214.e15. https://doi.org/10.1016/j.neurobiolaging.2016.08.023

@article{3af1546ed5d848cc8993b1433f469405,

title = "Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies",

abstract = "C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB.",

keywords = "C9orf72, Dementia with Lewy bodies (DLB), Genetic screen",

author = "Celia Kun-Rodrigues and Ross, {Owen A.} and Tatiana Orme and Claire Shepherd and Laura Parkkinen and Lee Darwent and Dena Hernandez and Olaf Ansorge and Clark, {Lorraine N.} and Honig, {Lawrence S.} and Karen Marder and Afina Lemstra and Philippe Scheltens and {van der Flier}, Wiesje and Eva Louwersheimer and Henne Holstege and Ekaterina Rogaeva and {St. George-Hyslop}, Peter and Elisabet Londos and Henrik Zetterberg and Imelda Barber and Anne Braae and Kristelle Brown and Kevin Morgan and Walter Maetzler and Daniela Berg and Claire Troakes and Safa Al-Sarraj and Tammaryn Lashley and Janice Holton and Yaroslau Compta and {Van Deerlin}, Vivianna and Trojanowski, {John Q.} and Serrano, {Geidy E.} and Beach, {Thomas G.} and Jordi Clarimon and Alberto Lle{\'o} and Estrella Morenas-Rodr{\'i}guez and Suzanne Lesage and Douglas Galasko and Eliezer Masliah and Isabel Santana and Monica Diez and Pau Pastor and Tienari, {Pentti J.} and Liisa Myllykangas and Minna Oinas and Tamas Revesz and Andrew Lees and Boeve, {Brad F.} and Petersen, {Ronald C.} and Ferman, {Tanis J.} and Valentina Escott-Price and Neill Graff-Radford and Cairns, {Nigel J.} and Morris, {John C.} and Stone, {David J.} and Stuart Pickering-Brown and David Mann and Dickson, {Dennis W.} and Halliday, {Glenda M.} and Andrew Singleton and Rita Guerreiro and Jose Bras",

note = "Funding Information: This work was supported in part by the National Institutes of Neurological Disease and Stroke. Jose Bras and Rita Guerreiro are supported by fellowships from the Alzheimer's Society. Tatiana Orme is supported by a scholarship from the Lewy Body Society. For the neuropathologically confirmed samples from Australia, tissues were received from the Sydney Brain Bank, which is supported by Neuroscience Research Australia and the University of New South Wales. This study was also partially funded by the Wellcome Trust, Medical Research Council, Canadian Institutes of Health Research, and Ontario Research Fund. The Nottingham Genetics Group is supported by ARUK and The Big Lottery Fund. The effort from Columbia University was supported by the Taub Institute, the Panasci Fund, the Parkinson's Disease Foundation, and NIH grants NS060113 (Dr Clark), P50AG008702 (P.I. Scott Small), P50NS038370 (P.I.R. Burke), and UL1TR000040 (P.I.H. Ginsberg). Dr Ross is supported by the Michael J. Fox Foundation for Parkinson's Research, NINDS R01# NS078086. The Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS072187) and is supported by The Little Family Foundation and by the Mangurian Foundation Program for Lewy Body Dementia research and the Alzheimer Disease Research Center (P50 AG016547). The work from the Mayo Clinic Rochester is supported by the National Institute on Aging (P50 AG016574 and U01 AG006786). This work has received support from The Queen Square Brain Bank at the UCL Institute of Neurology; where Dr Lashley is funded by an ARUK senior fellowship. Some of the tissue samples studied were provided by the MRC London Neurodegenerative Diseases Brain Bank and the Brains for Dementia Research project (funded by Alzheimer's Society and ARUK). This research was supported in part by both the NIHR UCLH Biomedical Research Centre and the Queen Square Dementia Biomedical Research Unit. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project AG000951-12. The University of Pennsylvania case collection is funded by the Penn Alzheimer's Disease Core Center (AG10124) and the Penn Morris K. Udall Parkinson's Disease Research Center (NS053488). The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. Tissue samples from UCSD are supported by NIH grant AG05131. The authors thank the brain bank GIE NeuroCEB, the French program “Investissements d'avenir” (ANR-10-IAIHU-06). Dr Tienari and Dr Myllykangas are supported by the Helsinki University Central Hospital, the Folkh{\"a}lsan Research Foundation and the Finnish Academy. This work was in part supported by the Canadian Consortium on Neurodegeneration in Aging (ER). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2017",

month = jan,

day = "1",

doi = "10.1016/j.neurobiolaging.2016.08.023",

language = "English (US)",

volume = "49",

pages = "214.e13--214.e15",

journal = "Neurobiology of aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

AU - Kun-Rodrigues, Celia

AU - Ross, Owen A.

AU - Orme, Tatiana

AU - Shepherd, Claire

AU - Parkkinen, Laura

AU - Darwent, Lee

AU - Hernandez, Dena

AU - Ansorge, Olaf

AU - Clark, Lorraine N.

AU - Honig, Lawrence S.

AU - Marder, Karen

AU - Lemstra, Afina

AU - Scheltens, Philippe

AU - van der Flier, Wiesje

AU - Louwersheimer, Eva

AU - Holstege, Henne

AU - Rogaeva, Ekaterina

AU - St. George-Hyslop, Peter

AU - Londos, Elisabet

AU - Zetterberg, Henrik

AU - Barber, Imelda

AU - Braae, Anne

AU - Brown, Kristelle

AU - Morgan, Kevin

AU - Maetzler, Walter

AU - Berg, Daniela

AU - Troakes, Claire

AU - Al-Sarraj, Safa

AU - Lashley, Tammaryn

AU - Holton, Janice

AU - Compta, Yaroslau

AU - Van Deerlin, Vivianna

AU - Trojanowski, John Q.

AU - Serrano, Geidy E.

AU - Beach, Thomas G.

AU - Clarimon, Jordi

AU - Lleó, Alberto

AU - Morenas-Rodríguez, Estrella

AU - Lesage, Suzanne

AU - Galasko, Douglas

AU - Masliah, Eliezer

AU - Santana, Isabel

AU - Diez, Monica

AU - Pastor, Pau

AU - Tienari, Pentti J.

AU - Myllykangas, Liisa

AU - Oinas, Minna

AU - Revesz, Tamas

AU - Lees, Andrew

AU - Boeve, Brad F.

AU - Petersen, Ronald C.

AU - Ferman, Tanis J.

AU - Escott-Price, Valentina

AU - Graff-Radford, Neill

AU - Cairns, Nigel J.

AU - Morris, John C.

AU - Stone, David J.

AU - Pickering-Brown, Stuart

AU - Mann, David

AU - Dickson, Dennis W.

AU - Halliday, Glenda M.

AU - Singleton, Andrew

AU - Guerreiro, Rita

AU - Bras, Jose

N1 - Funding Information: This work was supported in part by the National Institutes of Neurological Disease and Stroke. Jose Bras and Rita Guerreiro are supported by fellowships from the Alzheimer's Society. Tatiana Orme is supported by a scholarship from the Lewy Body Society. For the neuropathologically confirmed samples from Australia, tissues were received from the Sydney Brain Bank, which is supported by Neuroscience Research Australia and the University of New South Wales. This study was also partially funded by the Wellcome Trust, Medical Research Council, Canadian Institutes of Health Research, and Ontario Research Fund. The Nottingham Genetics Group is supported by ARUK and The Big Lottery Fund. The effort from Columbia University was supported by the Taub Institute, the Panasci Fund, the Parkinson's Disease Foundation, and NIH grants NS060113 (Dr Clark), P50AG008702 (P.I. Scott Small), P50NS038370 (P.I.R. Burke), and UL1TR000040 (P.I.H. Ginsberg). Dr Ross is supported by the Michael J. Fox Foundation for Parkinson's Research, NINDS R01# NS078086. The Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence (NINDS P50 #NS072187) and is supported by The Little Family Foundation and by the Mangurian Foundation Program for Lewy Body Dementia research and the Alzheimer Disease Research Center (P50 AG016547). The work from the Mayo Clinic Rochester is supported by the National Institute on Aging (P50 AG016574 and U01 AG006786). This work has received support from The Queen Square Brain Bank at the UCL Institute of Neurology; where Dr Lashley is funded by an ARUK senior fellowship. Some of the tissue samples studied were provided by the MRC London Neurodegenerative Diseases Brain Bank and the Brains for Dementia Research project (funded by Alzheimer's Society and ARUK). This research was supported in part by both the NIHR UCLH Biomedical Research Centre and the Queen Square Dementia Biomedical Research Unit. This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project AG000951-12. The University of Pennsylvania case collection is funded by the Penn Alzheimer's Disease Core Center (AG10124) and the Penn Morris K. Udall Parkinson's Disease Research Center (NS053488). The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. Tissue samples from UCSD are supported by NIH grant AG05131. The authors thank the brain bank GIE NeuroCEB, the French program “Investissements d'avenir” (ANR-10-IAIHU-06). Dr Tienari and Dr Myllykangas are supported by the Helsinki University Central Hospital, the Folkhälsan Research Foundation and the Finnish Academy. This work was in part supported by the Canadian Consortium on Neurodegeneration in Aging (ER). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB.

AB - C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB.

KW - C9orf72

KW - Dementia with Lewy bodies (DLB)

KW - Genetic screen

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DO - 10.1016/j.neurobiolaging.2016.08.023

M3 - Article

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AN - SCOPUS:84995602250

SN - 0197-4580

VL - 49

SP - 214.e13-214.e15

JO - Neurobiology of aging

JF - Neurobiology of aging

ER -

Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies

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