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Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration

OBJECTIVE: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)–causing mutations at risk of disease progression. METHODS: Baseline plasma NfL concentrations were measured with single-molecule array...

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Autores principales: Rojas, Julio C., Wang, Ping, Staffaroni, Adam M., Heller, Carolin, Cobigo, Yann, Wolf, Amy, Goh, Sheng-Yang M., Ljubenkov, Peter A., Heuer, Hilary W., Fong, Jamie C., Taylor, Joanne B., Veras, Eliseo, Song, Linan, Jeromin, Andreas, Hanlon, David, Yu, Lili, Khinikar, Arvind, Sivasankaran, Rajeev, Kieloch, Agnieszka, Valentin, Marie-Anne, Karydas, Anna M., Mitic, Laura L., Pearlman, Rodney, Kornak, John, Kramer, Joel H., Miller, Bruce L., Kantarci, Kejal, Knopman, David S., Graff-Radford, Neill, Petrucelli, Leonard, Rademakers, Rosa, Irwin, David J., Grossman, Murray, Ramos, Eliana Marisa, Coppola, Giovanni, Mendez, Mario F., Bordelon, Yvette, Dickerson, Bradford C., Ghoshal, Nupur, Huey, Edward D., Mackenzie, Ian R., Appleby, Brian S., Domoto-Reilly, Kimiko, Hsiung, Ging-Yuek R., Toga, Arthur W., Weintraub, Sandra, Kaufer, Daniel I., Kerwin, Diana, Litvan, Irene, Onyike, Chiadikaobi U., Pantelyat, Alexander, Roberson, Erik D., Tartaglia, Maria C., Foroud, Tatiana, Chen, Weiping, Czerkowicz, Julie, Graham, Danielle L., van Swieten, John C., Borroni, Barbara, Sanchez-Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Synofzik, Matthis, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Finger, Elizabeth, Vandenberghe, Rik, de Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Sorbi, Sandro, Cash, David M., Convery, Rhian S., Bocchetta, Martina, Foiani, Martha, Greaves, Caroline V., Peakman, Georgia, Russell, Lucy, Swift, Imogen, Todd, Emily, Rohrer, Jonathan D., Boeve, Bradley F., Rosen, Howard J., Boxer, Adam L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166434/
https://www.ncbi.nlm.nih.gov/pubmed/33827960
http://dx.doi.org/10.1212/WNL.0000000000011848
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author Rojas, Julio C.
Wang, Ping
Staffaroni, Adam M.
Heller, Carolin
Cobigo, Yann
Wolf, Amy
Goh, Sheng-Yang M.
Ljubenkov, Peter A.
Heuer, Hilary W.
Fong, Jamie C.
Taylor, Joanne B.
Veras, Eliseo
Song, Linan
Jeromin, Andreas
Hanlon, David
Yu, Lili
Khinikar, Arvind
Sivasankaran, Rajeev
Kieloch, Agnieszka
Valentin, Marie-Anne
Karydas, Anna M.
Mitic, Laura L.
Pearlman, Rodney
Kornak, John
Kramer, Joel H.
Miller, Bruce L.
Kantarci, Kejal
Knopman, David S.
Graff-Radford, Neill
Petrucelli, Leonard
Rademakers, Rosa
Irwin, David J.
Grossman, Murray
Ramos, Eliana Marisa
Coppola, Giovanni
Mendez, Mario F.
Bordelon, Yvette
Dickerson, Bradford C.
Ghoshal, Nupur
Huey, Edward D.
Mackenzie, Ian R.
Appleby, Brian S.
Domoto-Reilly, Kimiko
Hsiung, Ging-Yuek R.
Toga, Arthur W.
Weintraub, Sandra
Kaufer, Daniel I.
Kerwin, Diana
Litvan, Irene
Onyike, Chiadikaobi U.
Pantelyat, Alexander
Roberson, Erik D.
Tartaglia, Maria C.
Foroud, Tatiana
Chen, Weiping
Czerkowicz, Julie
Graham, Danielle L.
van Swieten, John C.
Borroni, Barbara
Sanchez-Valle, Raquel
Moreno, Fermin
Laforce, Robert
Graff, Caroline
Synofzik, Matthis
Galimberti, Daniela
Rowe, James B.
Masellis, Mario
Finger, Elizabeth
Vandenberghe, Rik
de Mendonça, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Chris R.
Gerhard, Alexander
Levin, Johannes
Danek, Adrian
Otto, Markus
Sorbi, Sandro
Cash, David M.
Convery, Rhian S.
Bocchetta, Martina
Foiani, Martha
Greaves, Caroline V.
Peakman, Georgia
Russell, Lucy
Swift, Imogen
Todd, Emily
Rohrer, Jonathan D.
Boeve, Bradley F.
Rosen, Howard J.
Boxer, Adam L.
author_facet Rojas, Julio C.
Wang, Ping
Staffaroni, Adam M.
Heller, Carolin
Cobigo, Yann
Wolf, Amy
Goh, Sheng-Yang M.
Ljubenkov, Peter A.
Heuer, Hilary W.
Fong, Jamie C.
Taylor, Joanne B.
Veras, Eliseo
Song, Linan
Jeromin, Andreas
Hanlon, David
Yu, Lili
Khinikar, Arvind
Sivasankaran, Rajeev
Kieloch, Agnieszka
Valentin, Marie-Anne
Karydas, Anna M.
Mitic, Laura L.
Pearlman, Rodney
Kornak, John
Kramer, Joel H.
Miller, Bruce L.
Kantarci, Kejal
Knopman, David S.
Graff-Radford, Neill
Petrucelli, Leonard
Rademakers, Rosa
Irwin, David J.
Grossman, Murray
Ramos, Eliana Marisa
Coppola, Giovanni
Mendez, Mario F.
Bordelon, Yvette
Dickerson, Bradford C.
Ghoshal, Nupur
Huey, Edward D.
Mackenzie, Ian R.
Appleby, Brian S.
Domoto-Reilly, Kimiko
Hsiung, Ging-Yuek R.
Toga, Arthur W.
Weintraub, Sandra
Kaufer, Daniel I.
Kerwin, Diana
Litvan, Irene
Onyike, Chiadikaobi U.
Pantelyat, Alexander
Roberson, Erik D.
Tartaglia, Maria C.
Foroud, Tatiana
Chen, Weiping
Czerkowicz, Julie
Graham, Danielle L.
van Swieten, John C.
Borroni, Barbara
Sanchez-Valle, Raquel
Moreno, Fermin
Laforce, Robert
Graff, Caroline
Synofzik, Matthis
Galimberti, Daniela
Rowe, James B.
Masellis, Mario
Finger, Elizabeth
Vandenberghe, Rik
de Mendonça, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Chris R.
Gerhard, Alexander
Levin, Johannes
Danek, Adrian
Otto, Markus
Sorbi, Sandro
Cash, David M.
Convery, Rhian S.
Bocchetta, Martina
Foiani, Martha
Greaves, Caroline V.
Peakman, Georgia
Russell, Lucy
Swift, Imogen
Todd, Emily
Rohrer, Jonathan D.
Boeve, Bradley F.
Rosen, Howard J.
Boxer, Adam L.
author_sort Rojas, Julio C.
collection PubMed
description OBJECTIVE: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)–causing mutations at risk of disease progression. METHODS: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables. RESULTS: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers. CONCLUSIONS: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression.
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spelling pubmed-81664342021-06-01 Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration Rojas, Julio C. Wang, Ping Staffaroni, Adam M. Heller, Carolin Cobigo, Yann Wolf, Amy Goh, Sheng-Yang M. Ljubenkov, Peter A. Heuer, Hilary W. Fong, Jamie C. Taylor, Joanne B. Veras, Eliseo Song, Linan Jeromin, Andreas Hanlon, David Yu, Lili Khinikar, Arvind Sivasankaran, Rajeev Kieloch, Agnieszka Valentin, Marie-Anne Karydas, Anna M. Mitic, Laura L. Pearlman, Rodney Kornak, John Kramer, Joel H. Miller, Bruce L. Kantarci, Kejal Knopman, David S. Graff-Radford, Neill Petrucelli, Leonard Rademakers, Rosa Irwin, David J. Grossman, Murray Ramos, Eliana Marisa Coppola, Giovanni Mendez, Mario F. Bordelon, Yvette Dickerson, Bradford C. Ghoshal, Nupur Huey, Edward D. Mackenzie, Ian R. Appleby, Brian S. Domoto-Reilly, Kimiko Hsiung, Ging-Yuek R. Toga, Arthur W. Weintraub, Sandra Kaufer, Daniel I. Kerwin, Diana Litvan, Irene Onyike, Chiadikaobi U. Pantelyat, Alexander Roberson, Erik D. Tartaglia, Maria C. Foroud, Tatiana Chen, Weiping Czerkowicz, Julie Graham, Danielle L. van Swieten, John C. Borroni, Barbara Sanchez-Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Synofzik, Matthis Galimberti, Daniela Rowe, James B. Masellis, Mario Finger, Elizabeth Vandenberghe, Rik de Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R. Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Sorbi, Sandro Cash, David M. Convery, Rhian S. Bocchetta, Martina Foiani, Martha Greaves, Caroline V. Peakman, Georgia Russell, Lucy Swift, Imogen Todd, Emily Rohrer, Jonathan D. Boeve, Bradley F. Rosen, Howard J. Boxer, Adam L. Neurology Article OBJECTIVE: We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)–causing mutations at risk of disease progression. METHODS: Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN, and MAPT mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables. RESULTS: In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL, p = 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL, p = 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers. CONCLUSIONS: Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression. Lippincott Williams & Wilkins 2021-05-04 /pmc/articles/PMC8166434/ /pubmed/33827960 http://dx.doi.org/10.1212/WNL.0000000000011848 Text en Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Rojas, Julio C.
Wang, Ping
Staffaroni, Adam M.
Heller, Carolin
Cobigo, Yann
Wolf, Amy
Goh, Sheng-Yang M.
Ljubenkov, Peter A.
Heuer, Hilary W.
Fong, Jamie C.
Taylor, Joanne B.
Veras, Eliseo
Song, Linan
Jeromin, Andreas
Hanlon, David
Yu, Lili
Khinikar, Arvind
Sivasankaran, Rajeev
Kieloch, Agnieszka
Valentin, Marie-Anne
Karydas, Anna M.
Mitic, Laura L.
Pearlman, Rodney
Kornak, John
Kramer, Joel H.
Miller, Bruce L.
Kantarci, Kejal
Knopman, David S.
Graff-Radford, Neill
Petrucelli, Leonard
Rademakers, Rosa
Irwin, David J.
Grossman, Murray
Ramos, Eliana Marisa
Coppola, Giovanni
Mendez, Mario F.
Bordelon, Yvette
Dickerson, Bradford C.
Ghoshal, Nupur
Huey, Edward D.
Mackenzie, Ian R.
Appleby, Brian S.
Domoto-Reilly, Kimiko
Hsiung, Ging-Yuek R.
Toga, Arthur W.
Weintraub, Sandra
Kaufer, Daniel I.
Kerwin, Diana
Litvan, Irene
Onyike, Chiadikaobi U.
Pantelyat, Alexander
Roberson, Erik D.
Tartaglia, Maria C.
Foroud, Tatiana
Chen, Weiping
Czerkowicz, Julie
Graham, Danielle L.
van Swieten, John C.
Borroni, Barbara
Sanchez-Valle, Raquel
Moreno, Fermin
Laforce, Robert
Graff, Caroline
Synofzik, Matthis
Galimberti, Daniela
Rowe, James B.
Masellis, Mario
Finger, Elizabeth
Vandenberghe, Rik
de Mendonça, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Chris R.
Gerhard, Alexander
Levin, Johannes
Danek, Adrian
Otto, Markus
Sorbi, Sandro
Cash, David M.
Convery, Rhian S.
Bocchetta, Martina
Foiani, Martha
Greaves, Caroline V.
Peakman, Georgia
Russell, Lucy
Swift, Imogen
Todd, Emily
Rohrer, Jonathan D.
Boeve, Bradley F.
Rosen, Howard J.
Boxer, Adam L.
Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
title Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
title_full Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
title_fullStr Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
title_full_unstemmed Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
title_short Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration
title_sort plasma neurofilament light for prediction of disease progression in familial frontotemporal lobar degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166434/
https://www.ncbi.nlm.nih.gov/pubmed/33827960
http://dx.doi.org/10.1212/WNL.0000000000011848
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AT rohrerjonathand plasmaneurofilamentlightforpredictionofdiseaseprogressioninfamilialfrontotemporallobardegeneration
AT boevebradleyf plasmaneurofilamentlightforpredictionofdiseaseprogressioninfamilialfrontotemporallobardegeneration
AT rosenhowardj plasmaneurofilamentlightforpredictionofdiseaseprogressioninfamilialfrontotemporallobardegeneration
AT boxeradaml plasmaneurofilamentlightforpredictionofdiseaseprogressioninfamilialfrontotemporallobardegeneration
AT plasmaneurofilamentlightforpredictionofdiseaseprogressioninfamilialfrontotemporallobardegeneration