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Serum Neurofilament Light in Patients with Frontotemporal Dementia Caused by CHMP2B Mutation

Authors
  • Toft, Anders
  • Roos, Peter
  • Jääskeläinen, Olli
  • Musaeus, Christian Sandøe
  • Henriksen, Emil Elbæk
  • Johannsen, Peter
  • Nielsen, Troels Tolstrup
  • Herukka, Sanna-Kaisa
  • Hviid Simonsen, Anja
  • Nielsen, Jørgen Erik
Type
Published Article
Journal
Dementia and Geriatric Cognitive Disorders
Publisher
S. Karger AG
Publication Date
Feb 24, 2021
Volume
49
Issue
6
Pages
533–538
Identifiers
DOI: 10.1159/000513877
PMID: 33626531
Source
Karger
Keywords
License
Green
External links

Abstract

Introduction: The potential of neurofilament light (NfL) as a blood-based biomarker is currently being investigated in autosomal dominant neurodegenerative disease. This study explores the clinical utility of serum-NfL in frontotemporal dementia due to CHMP2B mutation (FTD-3). Methods: This cross-sectional study included serum and CSF data from 38 members of the Danish FTD-3 family: 12 affected CHMP2B mutation carriers, 10 presymptomatic carriers, and 16 noncarriers. Serum-NfL levels measured by single-molecule array (Simoa) technology were tested for associations with the clinical groups and clinical parameters. Serum and CSF data were compared, and CSF/serum-albumin ratio was included as a measure of blood-brain barrier (BBB) function. Results: Serum-NfL concentrations were significantly increased in symptomatic CHMP2B mutation carriers compared to presymptomatic carriers and in both groups compared to healthy family controls. Serum-NfL levels appear to increase progressively with age in presymptomatic carriers, and this is perhaps followed by a change in trajectory when patients become symptomatic. Measurements of NfL in serum and CSF were highly correlated and fold-changes in serum and CSF between clinical groups were similar. Increase in serum-NFL levels was correlated with reduced ACE-score. Higher CSF/serum-albumin ratios were demonstrated in FTD-3 patients, but this did not affect the significant associations between serum-NfL and clinical groups. Conclusion: Serum-NfL could be utilized as an accurate surrogate marker of CSF levels to segregate symptomatic CHMP2B carriers, presymptomatic carriers, and non-carriers. The observed indication of BBB dysfunction in FTD-3 patients did not confound this use of serum-NfL. The results support the occurrence of mutation-related differences in NfL dynamics in familial FTD.

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