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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| Veröffentlicht in: | NEUROLOGY 2021-05, Vol.96 (18), p.E2296-E2312 |
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| creator | 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 Mendonca, 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 |
| 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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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.</description><identifier>ISSN: 0028-3878</identifier><language>eng</language><publisher>LIPPINCOTT WILLIAMS & WILKINS</publisher><ispartof>NEUROLOGY, 2021-05, Vol.96 (18), p.E2296-E2312</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,315,780,784,27860</link.rule.ids></links><search><creatorcontrib>Rojas, Julio C</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Staffaroni, Adam M</creatorcontrib><creatorcontrib>Heller, Carolin</creatorcontrib><creatorcontrib>Cobigo, Yann</creatorcontrib><creatorcontrib>Wolf, Amy</creatorcontrib><creatorcontrib>Goh, Sheng-Yang M</creatorcontrib><creatorcontrib>Ljubenkov, Peter A</creatorcontrib><creatorcontrib>Heuer, Hilary W</creatorcontrib><creatorcontrib>Fong, Jamie C</creatorcontrib><creatorcontrib>Taylor, Joanne B</creatorcontrib><creatorcontrib>Veras, Eliseo</creatorcontrib><creatorcontrib>Song, Linan</creatorcontrib><creatorcontrib>Jeromin, Andreas</creatorcontrib><creatorcontrib>Hanlon, David</creatorcontrib><creatorcontrib>Yu, Lili</creatorcontrib><creatorcontrib>Khinikar, Arvind</creatorcontrib><creatorcontrib>Sivasankaran, Rajeev</creatorcontrib><creatorcontrib>Kieloch, Agnieszka</creatorcontrib><creatorcontrib>Valentin, Marie-Anne</creatorcontrib><creatorcontrib>Karydas, Anna M</creatorcontrib><creatorcontrib>Mitic, Laura L</creatorcontrib><creatorcontrib>Pearlman, Rodney</creatorcontrib><creatorcontrib>Kornak, John</creatorcontrib><creatorcontrib>Kramer, Joel H</creatorcontrib><creatorcontrib>Miller, Bruce L</creatorcontrib><creatorcontrib>Kantarci, Kejal</creatorcontrib><creatorcontrib>Knopman, David S</creatorcontrib><creatorcontrib>Graff-Radford, Neill</creatorcontrib><creatorcontrib>Petrucelli, Leonard</creatorcontrib><creatorcontrib>Rademakers, Rosa</creatorcontrib><creatorcontrib>Irwin, David J</creatorcontrib><creatorcontrib>Grossman, Murray</creatorcontrib><creatorcontrib>Ramos, Eliana Marisa</creatorcontrib><creatorcontrib>Coppola, Giovanni</creatorcontrib><creatorcontrib>Mendez, Mario F</creatorcontrib><creatorcontrib>Bordelon, Yvette</creatorcontrib><creatorcontrib>Dickerson, Bradford C</creatorcontrib><creatorcontrib>Ghoshal, Nupur</creatorcontrib><creatorcontrib>Huey, Edward D</creatorcontrib><creatorcontrib>Mackenzie, Ian R</creatorcontrib><creatorcontrib>Appleby, Brian S</creatorcontrib><creatorcontrib>Domoto-Reilly, Kimiko</creatorcontrib><creatorcontrib>Hsiung, Ging-Yuek R</creatorcontrib><creatorcontrib>Toga, Arthur W</creatorcontrib><creatorcontrib>Weintraub, Sandra</creatorcontrib><creatorcontrib>Kaufer, Daniel I</creatorcontrib><creatorcontrib>Kerwin, Diana</creatorcontrib><creatorcontrib>Litvan, Irene</creatorcontrib><creatorcontrib>Onyike, Chiadikaobi U</creatorcontrib><creatorcontrib>Pantelyat, Alexander</creatorcontrib><creatorcontrib>Roberson, Erik D</creatorcontrib><creatorcontrib>Tartaglia, Maria C</creatorcontrib><creatorcontrib>Foroud, Tatiana</creatorcontrib><creatorcontrib>Chen, Weiping</creatorcontrib><creatorcontrib>Czerkowicz, Julie</creatorcontrib><creatorcontrib>Graham, Danielle L</creatorcontrib><creatorcontrib>van Swieten, John C</creatorcontrib><creatorcontrib>Borroni, Barbara</creatorcontrib><creatorcontrib>Sanchez-Valle, Raquel</creatorcontrib><creatorcontrib>Moreno, Fermin</creatorcontrib><creatorcontrib>Laforce, Robert</creatorcontrib><creatorcontrib>Graff, Caroline</creatorcontrib><creatorcontrib>Synofzik, Matthis</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Rowe, James B</creatorcontrib><creatorcontrib>Masellis, Mario</creatorcontrib><creatorcontrib>Finger, Elizabeth</creatorcontrib><creatorcontrib>Vandenberghe, Rik</creatorcontrib><creatorcontrib>de Mendonca, Alexandre</creatorcontrib><creatorcontrib>Tagliavini, Fabrizio</creatorcontrib><creatorcontrib>Santana, Isabel</creatorcontrib><creatorcontrib>Ducharme, Simon</creatorcontrib><creatorcontrib>Butler, Chris R</creatorcontrib><creatorcontrib>Gerhard, Alexander</creatorcontrib><creatorcontrib>Levin, Johannes</creatorcontrib><creatorcontrib>Danek, Adrian</creatorcontrib><creatorcontrib>Otto, Markus</creatorcontrib><creatorcontrib>Sorbi, Sandro</creatorcontrib><creatorcontrib>Cash, David M</creatorcontrib><creatorcontrib>Convery, Rhian S</creatorcontrib><creatorcontrib>Bocchetta, Martina</creatorcontrib><creatorcontrib>Foiani, Martha</creatorcontrib><creatorcontrib>Greaves, Caroline V</creatorcontrib><creatorcontrib>Peakman, Georgia</creatorcontrib><creatorcontrib>Russell, Lucy</creatorcontrib><creatorcontrib>Swift, Imogen</creatorcontrib><creatorcontrib>Todd, Emily</creatorcontrib><creatorcontrib>Rohrer, Jonathan D</creatorcontrib><creatorcontrib>Boeve, Bradley F</creatorcontrib><creatorcontrib>Rosen, Howard J</creatorcontrib><creatorcontrib>Boxer, Adam L</creatorcontrib><title>Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration</title><title>NEUROLOGY</title><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.</description><issn>0028-3878</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>FZOIL</sourceid><recordid>eNqVjLGqwkAQRbfwgfr0H6azECEmxl1rNViIWNiHUSdxdbMjOxvx81V4H_CsLudwuB3VS5LUTDKjTVf1Ra5JMs1Tvegpv3coDcKO2sCVddiQj7C19SVCxQH2gc72FC174ApWVgiF3pbrQCIfbT0U2Fhn0UER2EeO1Nw5vHHLRwywopo8BfycDNRPhU5o-Le_alSsD8vN5NY6ah_ky7Pc8UTlNM1m-VybRTnXs9zo7Jty_L-yjM-YvQDL9Fi2</recordid><startdate>20210504</startdate><enddate>20210504</enddate><creator>Rojas, Julio C</creator><creator>Wang, Ping</creator><creator>Staffaroni, Adam M</creator><creator>Heller, Carolin</creator><creator>Cobigo, Yann</creator><creator>Wolf, Amy</creator><creator>Goh, Sheng-Yang M</creator><creator>Ljubenkov, Peter A</creator><creator>Heuer, Hilary 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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 Mendonca, 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><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-kuleuven_dspace_123456789_6745873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rojas, Julio C</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Staffaroni, Adam M</creatorcontrib><creatorcontrib>Heller, Carolin</creatorcontrib><creatorcontrib>Cobigo, Yann</creatorcontrib><creatorcontrib>Wolf, Amy</creatorcontrib><creatorcontrib>Goh, Sheng-Yang M</creatorcontrib><creatorcontrib>Ljubenkov, Peter A</creatorcontrib><creatorcontrib>Heuer, Hilary W</creatorcontrib><creatorcontrib>Fong, Jamie C</creatorcontrib><creatorcontrib>Taylor, Joanne B</creatorcontrib><creatorcontrib>Veras, Eliseo</creatorcontrib><creatorcontrib>Song, Linan</creatorcontrib><creatorcontrib>Jeromin, Andreas</creatorcontrib><creatorcontrib>Hanlon, David</creatorcontrib><creatorcontrib>Yu, Lili</creatorcontrib><creatorcontrib>Khinikar, Arvind</creatorcontrib><creatorcontrib>Sivasankaran, Rajeev</creatorcontrib><creatorcontrib>Kieloch, Agnieszka</creatorcontrib><creatorcontrib>Valentin, Marie-Anne</creatorcontrib><creatorcontrib>Karydas, Anna M</creatorcontrib><creatorcontrib>Mitic, Laura L</creatorcontrib><creatorcontrib>Pearlman, Rodney</creatorcontrib><creatorcontrib>Kornak, John</creatorcontrib><creatorcontrib>Kramer, Joel H</creatorcontrib><creatorcontrib>Miller, Bruce L</creatorcontrib><creatorcontrib>Kantarci, Kejal</creatorcontrib><creatorcontrib>Knopman, David S</creatorcontrib><creatorcontrib>Graff-Radford, Neill</creatorcontrib><creatorcontrib>Petrucelli, Leonard</creatorcontrib><creatorcontrib>Rademakers, Rosa</creatorcontrib><creatorcontrib>Irwin, David J</creatorcontrib><creatorcontrib>Grossman, Murray</creatorcontrib><creatorcontrib>Ramos, Eliana Marisa</creatorcontrib><creatorcontrib>Coppola, Giovanni</creatorcontrib><creatorcontrib>Mendez, Mario F</creatorcontrib><creatorcontrib>Bordelon, Yvette</creatorcontrib><creatorcontrib>Dickerson, Bradford C</creatorcontrib><creatorcontrib>Ghoshal, Nupur</creatorcontrib><creatorcontrib>Huey, Edward D</creatorcontrib><creatorcontrib>Mackenzie, Ian R</creatorcontrib><creatorcontrib>Appleby, Brian S</creatorcontrib><creatorcontrib>Domoto-Reilly, Kimiko</creatorcontrib><creatorcontrib>Hsiung, Ging-Yuek R</creatorcontrib><creatorcontrib>Toga, Arthur W</creatorcontrib><creatorcontrib>Weintraub, Sandra</creatorcontrib><creatorcontrib>Kaufer, Daniel I</creatorcontrib><creatorcontrib>Kerwin, Diana</creatorcontrib><creatorcontrib>Litvan, Irene</creatorcontrib><creatorcontrib>Onyike, Chiadikaobi U</creatorcontrib><creatorcontrib>Pantelyat, Alexander</creatorcontrib><creatorcontrib>Roberson, Erik D</creatorcontrib><creatorcontrib>Tartaglia, Maria C</creatorcontrib><creatorcontrib>Foroud, Tatiana</creatorcontrib><creatorcontrib>Chen, Weiping</creatorcontrib><creatorcontrib>Czerkowicz, Julie</creatorcontrib><creatorcontrib>Graham, Danielle L</creatorcontrib><creatorcontrib>van Swieten, John C</creatorcontrib><creatorcontrib>Borroni, Barbara</creatorcontrib><creatorcontrib>Sanchez-Valle, Raquel</creatorcontrib><creatorcontrib>Moreno, Fermin</creatorcontrib><creatorcontrib>Laforce, Robert</creatorcontrib><creatorcontrib>Graff, Caroline</creatorcontrib><creatorcontrib>Synofzik, Matthis</creatorcontrib><creatorcontrib>Galimberti, Daniela</creatorcontrib><creatorcontrib>Rowe, James B</creatorcontrib><creatorcontrib>Masellis, Mario</creatorcontrib><creatorcontrib>Finger, Elizabeth</creatorcontrib><creatorcontrib>Vandenberghe, Rik</creatorcontrib><creatorcontrib>de Mendonca, Alexandre</creatorcontrib><creatorcontrib>Tagliavini, Fabrizio</creatorcontrib><creatorcontrib>Santana, Isabel</creatorcontrib><creatorcontrib>Ducharme, Simon</creatorcontrib><creatorcontrib>Butler, Chris R</creatorcontrib><creatorcontrib>Gerhard, Alexander</creatorcontrib><creatorcontrib>Levin, Johannes</creatorcontrib><creatorcontrib>Danek, Adrian</creatorcontrib><creatorcontrib>Otto, Markus</creatorcontrib><creatorcontrib>Sorbi, Sandro</creatorcontrib><creatorcontrib>Cash, David M</creatorcontrib><creatorcontrib>Convery, Rhian S</creatorcontrib><creatorcontrib>Bocchetta, Martina</creatorcontrib><creatorcontrib>Foiani, Martha</creatorcontrib><creatorcontrib>Greaves, Caroline V</creatorcontrib><creatorcontrib>Peakman, Georgia</creatorcontrib><creatorcontrib>Russell, Lucy</creatorcontrib><creatorcontrib>Swift, Imogen</creatorcontrib><creatorcontrib>Todd, Emily</creatorcontrib><creatorcontrib>Rohrer, Jonathan D</creatorcontrib><creatorcontrib>Boeve, Bradley F</creatorcontrib><creatorcontrib>Rosen, Howard J</creatorcontrib><creatorcontrib>Boxer, Adam L</creatorcontrib><collection>Lirias (KU Leuven Association)</collection><jtitle>NEUROLOGY</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rojas, Julio C</au><au>Wang, Ping</au><au>Staffaroni, Adam M</au><au>Heller, Carolin</au><au>Cobigo, Yann</au><au>Wolf, Amy</au><au>Goh, Sheng-Yang M</au><au>Ljubenkov, Peter A</au><au>Heuer, Hilary W</au><au>Fong, Jamie C</au><au>Taylor, Joanne B</au><au>Veras, Eliseo</au><au>Song, Linan</au><au>Jeromin, Andreas</au><au>Hanlon, David</au><au>Yu, Lili</au><au>Khinikar, Arvind</au><au>Sivasankaran, Rajeev</au><au>Kieloch, Agnieszka</au><au>Valentin, Marie-Anne</au><au>Karydas, Anna M</au><au>Mitic, Laura L</au><au>Pearlman, Rodney</au><au>Kornak, John</au><au>Kramer, Joel H</au><au>Miller, Bruce L</au><au>Kantarci, Kejal</au><au>Knopman, David S</au><au>Graff-Radford, Neill</au><au>Petrucelli, Leonard</au><au>Rademakers, Rosa</au><au>Irwin, David J</au><au>Grossman, Murray</au><au>Ramos, Eliana Marisa</au><au>Coppola, Giovanni</au><au>Mendez, Mario F</au><au>Bordelon, Yvette</au><au>Dickerson, Bradford C</au><au>Ghoshal, Nupur</au><au>Huey, Edward D</au><au>Mackenzie, Ian R</au><au>Appleby, Brian S</au><au>Domoto-Reilly, Kimiko</au><au>Hsiung, Ging-Yuek R</au><au>Toga, Arthur W</au><au>Weintraub, Sandra</au><au>Kaufer, Daniel I</au><au>Kerwin, Diana</au><au>Litvan, Irene</au><au>Onyike, Chiadikaobi U</au><au>Pantelyat, Alexander</au><au>Roberson, Erik D</au><au>Tartaglia, Maria C</au><au>Foroud, Tatiana</au><au>Chen, Weiping</au><au>Czerkowicz, Julie</au><au>Graham, Danielle L</au><au>van Swieten, John C</au><au>Borroni, Barbara</au><au>Sanchez-Valle, Raquel</au><au>Moreno, Fermin</au><au>Laforce, Robert</au><au>Graff, Caroline</au><au>Synofzik, Matthis</au><au>Galimberti, Daniela</au><au>Rowe, James B</au><au>Masellis, Mario</au><au>Finger, Elizabeth</au><au>Vandenberghe, Rik</au><au>de Mendonca, Alexandre</au><au>Tagliavini, Fabrizio</au><au>Santana, Isabel</au><au>Ducharme, Simon</au><au>Butler, Chris R</au><au>Gerhard, Alexander</au><au>Levin, Johannes</au><au>Danek, Adrian</au><au>Otto, Markus</au><au>Sorbi, Sandro</au><au>Cash, David M</au><au>Convery, Rhian S</au><au>Bocchetta, Martina</au><au>Foiani, Martha</au><au>Greaves, Caroline V</au><au>Peakman, Georgia</au><au>Russell, Lucy</au><au>Swift, Imogen</au><au>Todd, Emily</au><au>Rohrer, Jonathan D</au><au>Boeve, Bradley F</au><au>Rosen, Howard J</au><au>Boxer, Adam L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration</atitle><jtitle>NEUROLOGY</jtitle><date>2021-05-04</date><risdate>2021</risdate><volume>96</volume><issue>18</issue><spage>E2296</spage><epage>E2312</epage><pages>E2296-E2312</pages><issn>0028-3878</issn><abstract>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.</abstract><pub>LIPPINCOTT WILLIAMS & WILKINS</pub><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3878 |
| ispartof | NEUROLOGY, 2021-05, Vol.96 (18), p.E2296-E2312 |
| issn | 0028-3878 |
| language | eng |
| recordid | cdi_kuleuven_dspace_123456789_674587 |
| source | Lirias (KU Leuven Association); Alma/SFX Local Collection; Journals@Ovid Complete |
| title | Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T15%3A54%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-kuleuven&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Plasma%20Neurofilament%20Light%20for%20Prediction%20of%20Disease%20Progression%20in%20Familial%20Frontotemporal%20Lobar%20Degeneration&rft.jtitle=NEUROLOGY&rft.au=Rojas,%20Julio%20C&rft.date=2021-05-04&rft.volume=96&rft.issue=18&rft.spage=E2296&rft.epage=E2312&rft.pages=E2296-E2312&rft.issn=0028-3878&rft_id=info:doi/&rft_dat=%3Ckuleuven%3E123456789_674587%3C/kuleuven%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |