Open AccessNeurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia
Author(s) -
Kessler Christoph,
SernaHiguita Lina M.,
Rattay Tim W.,
Maetzler Walter,
Wurster Isabel,
Hayer Stefanie,
Wilke Carlo,
Hengel Holger,
Reichbauer Jennifer,
Armbruster Marcel,
Schöls Ludger,
Martus Peter,
Schüle Rebecca
Publication year - 2021
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51358
Subject(s) - medicine , cerebrospinal fluid , hereditary spastic paraplegia , paraplegia , biomarker , spastic , spasticity , gastroenterology , spinal cord , phenotype , physical therapy , genetics , cerebral palsy , biology , psychiatry , gene
Objective Despite the need for diagnostics and research, data on fluid biomarkers in hereditary spastic paraplegia (HSP) are scarce. We, therefore, explore Neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of patients with hereditary spastic paraplegia and provide information on the influence of demographic factors. Methods The study recruited 59 HSP cases (33 genetically confirmed) and 59 controls matched in age and sex. Neurofilament light chain levels were assessed by enzyme‐linked immunosorbent assay. The statistical analysis included the effects of age, sex, and genetic status (confirmed vs. not confirmed). Results Levels of CSF NfL were significantly increased in patients with hereditary spastic paraplegia compared to controls (median 741 pg/mL vs. 387 pg/mL, p < 0.001). Age (1.4% annual increase) and male sex (81% increase) impacted CSF NfL levels in patients. The age‐dependent increase of CSF NfL levels was steeper in controls (2.6% annual increase). Thus, the CSF NfL ratio of patients and matched controls—expressing patients’ fold increases in CSF NfL—declined considerably with age. Interpretation CSF NfL is a reliable cross‐sectional biomarker in hereditary spastic paraplegia. Sex is a relevant factor to consider, as male patients have remarkably higher CSF NfL levels. While levels also increase with age, the gap between patients and controls is narrowing in older subjects. This indicates distinct temporal dynamics of CSF NfL in patients with hereditary spastic paraplegia, with a rise around phenotypic conversion and comparatively static levels afterward.