Potential diagnostic HSP biomarker

Differences with gender and age identified

A potential biomarker for HSP that has been the subject of considerable study in motor neuron disease (MND) may prove to be valuable in diagnosing HSP and distinguishing it from similar conditions early in the course of the disease. Large differences were found in biomarker levels between males and females.

This biomarker study led by Dr Rebecca Schüle at the University of Tübingen in Germany received funding support from the HSP Research Foundation.

Rebecca Schüle

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.

SOURCE:  Ann Clin Transl Neurol. 2021 May;8(5):1122-1131. doi: 10.1002/acn3.51358. Epub 2021 Apr 5. PMID: 33819388 © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Neurofilament light chain is a cerebrospinal fluid biomarker in hereditary spastic paraplegia

Christoph Kessler  1   2   3 Lina M Serna-Higuita  4 Tim W Rattay  1   2   3 Walter Maetzler  5 Isabel Wurster  1   2   3 Stefanie Hayer  1   2   3 Carlo Wilke  1   2   3 Holger Hengel  1   2   3 Jennifer Reichbauer  1   2   3 Marcel Armbruster  2 Ludger Schöls  1   2   3 Peter Martus  4 Rebecca Schüle  1   2   3

1. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, Tübingen, Germany.

2. Center of Neurology, University of Tübingen, Tübingen, Germany.

3. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.

4. Department of Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany.

5. Department of Neurology, Kiel University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

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