The 5th Annual Congress of the European Academy of Neurology (EAN) in Oslo, Norway, featured an in-depth exploration of the role of neurofilament light chain (NfL) protein levels as a biomarker for morphological brain changes. Delivered by Michael Khalil (Department of Neurology, Medical University of Graz, Austria), the presentation showcased data examining age-dependent changes in brain function and neuronal injury.
Neuroaxonal damage and loss are the pathological substrates of many acute and chronic neurological disorders including multiple sclerosis, neurodegenerative dementia, stroke, traumatic brain injury, amyotrophic lateral sclerosis and Parkinson’s disease, leading to permanent disability.1 Because of this, there is great interest in methods that can reliably quantify and provide continued follow-up for neuroaxonal damage, thereby supporting the assessment of disease activity, response to treatment and ongoing prognosis.1
Neurofilaments – the cytoskeletal components of neurons that are particularly abundant in axons2 –are particularly promising due to their elevated levels in neuroaxonal damage both in the cerebrospinal fluid and in the blood/serum (sNfL).1 However, as Dr Khalili underlined, there is still limited knowledge regarding the association of sNfL with age and sub-clinical morphologic brain changes in the normal population.
With this in mind, Dr Khalil presented an investigation based on data and material from the prospective, ongoing Austrian Stroke Prevention Family Study (ASPS-Fam) – a population-based cohort study serving as an extension of the core ASPS investigation.3,4 In 335 healthy individuals (aged 38.5–85.5 years at study entry), sNfL was measured using a novel single molecule array (sensitive enough to detect serum NfL levels) with a mean follow up of 5.9 ± 1.0 years.5
Detailed clinical examination, laboratory evaluation, cognitive testing and brain MRI (3T) were performed to exclude any significant cerebral disorder, noted Dr Khalil, with white matter hyperintensity volumes, brain volumes and their changes over time measured as markers of subclinical brain damage.
Results revealed that mean sNfL levels increased with age in a normal, neurologically unsuspicious population. Specifically, levels were more stable in those under 60 years of age, while they increased non-linearly (including significant group variances and a wider distribution) in those older than 60. Baseline sNfL levels and their change over time were determined as the strongest independent predictors for future brain atrophy in those over 60, whilst baseline normalised brain volume was the strongest predictor for those under 60.
“Rising and more variable sNfL in individuals greater than 60 years indicate an acceleration of neuronal injury at higher age which may be driven by subclinical comorbid pathologies,” Dr Khalil commented. “This is supported by the close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner.”
Correlation between sNfL levels and atrophy of particular topographical brain areas is currently being actively investigated, Dr Khalil concluded, and more information will be fundamental in order to correctly interpret sNfL values in a variety of neurological disorders.
- Khalil M, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14(10):577–589.
- Varhaug KN, et al. Neurofilament Light Chain as a Biomarker in Multiple Sclerosis. Front Neurol. 2019; 10: 338.
- Schmidt R, et al. Assessment of Cerebrovascular Risk Profiles in Healthy Persons: Definition of Research Goals and the Austrian Stroke Prevention Study (ASPS). Neuroepidemiology 1994;13:308–313.
- Schmidt R, et al. MRI white matter hyperintensities: three-year follow-up of the Austrian Stroke Prevention Study. Neurology. 1999;53(1):132–9.
- Disanto G, et al. Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857–870.