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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.
Authors: Rojas, JC
Wang, P
Staffaroni, AM
Heller, C
Cobigo, Y
Wolf, A
Goh, S-YM
Ljubenkov, PA
Heuer, HW
Fong, JC
Taylor, JB
Veras, E
Song, L
Jeromin, A
Hanlon, D
Yu, L
Khinikar, A
Sivasankaran, R
Kieloch, A
Valentin, M-A
Karydas, AM
Mitic, LL
Pearlman, R
Kornak, J
Kramer, JH
Miller, BL
Kantarci, K
Knopman, DS
Graff-Radford, N
Petrucelli, L
Rademakers, R
Irwin, DJ
Grossman, M
Ramos, EM
Coppola, G
Mendez, MF
Bordelon, Y
Dickerson, BC
Ghoshal, N
Huey, ED
Mackenzie, IR
Appleby, BS
Domoto-Reilly, K
Hsiung, G-YR
Toga, AW
Weintraub, S
Kaufer, DI
Kerwin, D
Litvan, I
Onyike, CU
Pantelyat, A
Roberson, ED
Tartaglia, MC
Foroud, T
Chen, W
Czerkowicz, J
Graham, DL
Van Swieten, JC
Borroni, B
Sanchez-Valle, R
Moreno, F
Laforce, R
Graff, C
Synofzik, M
Galimberti, D
Rowe, JB
Masellis, M
Finger, E
Vandenberghe, R
De Mendonça, A
Tagliavini, F
Santana, I
Ducharme, S
Butler, CR
Gerhard, A
Levin, J
Danek, A
Otto, M
Sorbi, S
Cash, DM
Convery, RS
Bocchetta, M
Foiani, M
Greaves, CV
Peakman, G
Russell, L
Swift, I
Todd, E
Rohrer, JD
Boeve, BF
Rosen, HJ
Boxer, AL
ALLFTD and GENFI consortia
Item Type: Journal Article
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.
Issue Date: 4-May-2021
Date of Acceptance: 8-Feb-2021
URI: http://hdl.handle.net/10044/1/91146
DOI: 10.1212/WNL.0000000000011848
Start Page: e2296
End Page: e2312
Journal / Book Title: Neurology
Volume: 96
Issue: 18
Copyright Statement: © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Adult
Aged, 80 and over
Cohort Studies
Disease Progression
Frontotemporal Lobar Degeneration
Magnetic Resonance Imaging
Middle Aged
Neurofilament Proteins
Predictive Value of Tests
Young Adult
ALLFTD and GENFI consortia
Disease Progression
Neurofilament Proteins
Magnetic Resonance Imaging
Cohort Studies
Predictive Value of Tests
Aged, 80 and over
Middle Aged
Young Adult
Frontotemporal Lobar Degeneration
1103 Clinical Sciences
1109 Neurosciences
1702 Cognitive Sciences
Neurology & Neurosurgery
Publication Status: Published
Conference Place: United States
Appears in Collections:Department of Brain Sciences

This item is licensed under a Creative Commons License Creative Commons