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Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers

Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with muta...

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Autores principales: Popuri, Karteek, Dowds, Emma, Beg, Mirza Faisal, Balachandar, Rakesh, Bhalla, Mahadev, Jacova, Claudia, Buller, Adrienne, Slack, Penny, Sengdy, Pheth, Rademakers, Rosa, Wittenberg, Dana, Feldman, Howard H., Mackenzie, Ian R., Hsiung, Ging-Yuek R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964622/
https://www.ncbi.nlm.nih.gov/pubmed/29845007
http://dx.doi.org/10.1016/j.nicl.2018.02.017
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author Popuri, Karteek
Dowds, Emma
Beg, Mirza Faisal
Balachandar, Rakesh
Bhalla, Mahadev
Jacova, Claudia
Buller, Adrienne
Slack, Penny
Sengdy, Pheth
Rademakers, Rosa
Wittenberg, Dana
Feldman, Howard H.
Mackenzie, Ian R.
Hsiung, Ging-Yuek R.
author_facet Popuri, Karteek
Dowds, Emma
Beg, Mirza Faisal
Balachandar, Rakesh
Bhalla, Mahadev
Jacova, Claudia
Buller, Adrienne
Slack, Penny
Sengdy, Pheth
Rademakers, Rosa
Wittenberg, Dana
Feldman, Howard H.
Mackenzie, Ian R.
Hsiung, Ging-Yuek R.
author_sort Popuri, Karteek
collection PubMed
description Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with mutations in C9orf72 and granulin (GRN) genes. Clinically asymptomatic subjects from families with C9orf72 mutation (15 mutation carriers, C9orf72+; and 23 non-carriers, C9orf72−) and GRN mutations (9 mutation carriers, GRN+; and 15 non-carriers, GRN−) underwent structural neuroimaging (MRI). Cortical thickness and subcortical gray matter volumes were calculated using FreeSurfer. Group differences were evaluated, correcting for age, sex and years to mean age of disease onset within the subject's family. Mean age of C9orf72+ and C9orf72− were 42.6 ± 11.3 and 49.7 ± 15.5 years, respectively; while GRN+ and GRN− groups were 50.1 ± 8.7 and 53.2 ± 11.2 years respectively. The C9orf72+ group exhibited cortical thinning in the temporal, parietal and frontal regions, as well as reduced volumes of bilateral thalamus and left caudate compared to the entire group of mutation non-carriers (NC: C9orf72− and GRN− combined). In contrast, the GRN+ group did not show any significant differences compared to NC. C9orf72 mutation carriers demonstrate a pattern of reduced gray matter on MRI prior to symptom onset compared to GRN mutation carriers. These findings suggest that the preclinical course of FTD differs depending on the genetic basis and that the choice of neuroimaging biomarkers for FTD may need to take into account the specific genes involved in causing the disease.
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spelling pubmed-59646222018-05-29 Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers Popuri, Karteek Dowds, Emma Beg, Mirza Faisal Balachandar, Rakesh Bhalla, Mahadev Jacova, Claudia Buller, Adrienne Slack, Penny Sengdy, Pheth Rademakers, Rosa Wittenberg, Dana Feldman, Howard H. Mackenzie, Ian R. Hsiung, Ging-Yuek R. Neuroimage Clin Regular Article Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with mutations in C9orf72 and granulin (GRN) genes. Clinically asymptomatic subjects from families with C9orf72 mutation (15 mutation carriers, C9orf72+; and 23 non-carriers, C9orf72−) and GRN mutations (9 mutation carriers, GRN+; and 15 non-carriers, GRN−) underwent structural neuroimaging (MRI). Cortical thickness and subcortical gray matter volumes were calculated using FreeSurfer. Group differences were evaluated, correcting for age, sex and years to mean age of disease onset within the subject's family. Mean age of C9orf72+ and C9orf72− were 42.6 ± 11.3 and 49.7 ± 15.5 years, respectively; while GRN+ and GRN− groups were 50.1 ± 8.7 and 53.2 ± 11.2 years respectively. The C9orf72+ group exhibited cortical thinning in the temporal, parietal and frontal regions, as well as reduced volumes of bilateral thalamus and left caudate compared to the entire group of mutation non-carriers (NC: C9orf72− and GRN− combined). In contrast, the GRN+ group did not show any significant differences compared to NC. C9orf72 mutation carriers demonstrate a pattern of reduced gray matter on MRI prior to symptom onset compared to GRN mutation carriers. These findings suggest that the preclinical course of FTD differs depending on the genetic basis and that the choice of neuroimaging biomarkers for FTD may need to take into account the specific genes involved in causing the disease. Elsevier 2018-02-17 /pmc/articles/PMC5964622/ /pubmed/29845007 http://dx.doi.org/10.1016/j.nicl.2018.02.017 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
Popuri, Karteek
Dowds, Emma
Beg, Mirza Faisal
Balachandar, Rakesh
Bhalla, Mahadev
Jacova, Claudia
Buller, Adrienne
Slack, Penny
Sengdy, Pheth
Rademakers, Rosa
Wittenberg, Dana
Feldman, Howard H.
Mackenzie, Ian R.
Hsiung, Ging-Yuek R.
Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers
title Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers
title_full Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers
title_fullStr Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers
title_full_unstemmed Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers
title_short Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers
title_sort gray matter changes in asymptomatic c9orf72 and grn mutation carriers
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964622/
https://www.ncbi.nlm.nih.gov/pubmed/29845007
http://dx.doi.org/10.1016/j.nicl.2018.02.017
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