Plasma Neurofilament Light for Prediction of Disease Progression in Familial Frontotemporal Lobar Degeneration.
Neurology
; 96(18): e2296-e2312, 2021 05 04.
Article
in En
| MEDLINE
| ID: mdl-33827960
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neurofilament Proteins
/
Disease Progression
/
Frontotemporal Lobar Degeneration
Type of study:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Neurology
Year:
2021
Document type:
Article