Skip to main content

Plasma neurofilament light for prediction of disease progression in familial frontotemporal lobar degeneration

Cite this dataset

Rojas, Julio (2022). Plasma neurofilament light for prediction of disease progression in familial frontotemporal lobar degeneration [Dataset]. Dryad.


Objective: We tested the hypothesis that plasma neurofilament light chain (NfL) concentrations identify asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease progression.

Methods: Baseline plasma NfL concentrations were measured with Simoa in original (n = 277) and validation (n = 297) cohorts. C9orf72, GRN and MAPT mutation carriers and non-carriers 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 subsequent disease progression compared to non-progressors (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 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.

Classification of evidence: This study provides Class I evidence that in familial FTLD, elevation of plasma NfL predicts short-term risk of clinical progression.


The data was collected through clinical evaluation, measurement of biomarker in plasma and volumetric quantification of brain MRI.

Usage notes

These data supplement those in the main manuscript and are used to support the findings and conclusions.


National Institute on Aging, Award: U01 AG045390

National Institute of Neurological Disorders and Stroke, Award: U54 NS092089

National Institute on Aging, Award: K23AG059888

National Institute on Aging, Award: K23AG061253

Larry L. Hillblom Foundation, Award: 2018-A-025-FEL

National Institute on Aging, Award: U24 AG021886

National Institute on Aging, Award: U01 AG016976

MRC Clinician Scientist Fellowship, Award: MR/M008525/1

National Institute for Health Research, Award: BRC149/NS/MH

The National Brain Appeal, Award: RCN 290173

Alzheimer's Society, Award: AS-JF-19a-004-517

Swedish Research Council, Award: 2015-02926

German Research Foundation, Award: EXC 2145 SyNergy 390857198

MRC UK GENFI, Award: MR/M023664/1

JPND GENFI-PROX, Award: 2019-02248

European Reference Network for Rare Neurological Diseases , Award: 739510