Neurofilament light chain in patients with a concussion or head impacts: a systematic review and meta-analysis

Karantali, Eleni; Kazis, Dimitrios; McKenna, John F.; Chatzikonstantinou, Symela; Petridis, Fivos; Mavroudis, Ioannis

doi:10.1007/s00068-021-01693-1

Cited by 25 publications

(38 citation statements)

References 54 publications

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“…There have been 33 meta‐analyses on the wealth of data on Nf as a biomarker for neurodegeneration over the past 15 years (Agah et al, 2018; Alagaratnam, Widekind, et al, 2021; Angelopoulou et al, 2021; Arneth & Kraus, 2022; Cai & Huang, 2018; Choong et al, 2019; Cong et al, 2021; Forgrave et al, 2019; Gao et al, 2020b; Ge et al, 2018; Hoiland et al, 2022; Hu et al, 2017; Jin et al, 2019; Karantali, Kazis, Chatzikonstantinou, et al, 2021; Karantali, Kazis, McKenna, et al, 2021; Katayama et al, 2020; Koychev et al, 2021; Li et al, 2016; Liu et al, 2022; Liu, Chen, et al, 2020; Martin et al, 2019; Mondello et al, 2021; Peng et al, 2022; Petzold et al, 2007; Rübsamen et al, 2022; Sako et al, 2015; Sferruzza et al, 2021; Wang et al, 2019; Wang et al, 2020a; Wang et al, 2020b; Xu et al, 2016; Zhang et al, 2022; Zhao et al, 2019; Zhou et al, 2021).…”

Section: Meta‐analysesmentioning

confidence: 99%

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

Petzold

2022

Journal of Neurochemistry

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Neurofilament proteins (Nf) have been validated and established as a reliable body fluid biomarker for neurodegenerative pathology. This review covers seven Nf isoforms, Nf light (NfL), two splicing variants of Nf medium (NfM), two splicing variants of Nf heavy (NfH), -internexin (INA) and peripherin (PRPH). The genetic and epigenetic aspects of Nf are discussed as relevant for neurodegenerative diseases and oncology. The comprehensive list of mutations for all Nf isoforms covers Amyotrophic Lateral Sclerosis, Charcot-Marie Tooth disease, Spinal muscular atrophy, Parkinson Disease and Lewy Body Dementia. Next, emphasis is given to the expanding field of post-translational modifications (PTM) of the Nf amino acid residues. Protein structural aspects are reviewed alongside PTMs causing neurodegenerative pathology and human autoimmunity. Molecular visualisations of NF PTMs, assembly and stoichiometry make use of Alphafold2 modelling. The implications for Nf function on the cellular level and axonal transport are discussed. Neurofilament aggregate formation and proteolytic breakdown are reviewed as relevant for biomarker tests and disease.Likewise, Nf stoichiometry is reviewed with regard to in vitro experiments and as a compensatory mechanism in neurodegeneration. The review of Nf across a spectrum of 87 diseases from all parts of medicine is followed by a critical appraisal of 33

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Section: Meta‐analysesmentioning

confidence: 99%

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

Petzold

2022

Journal of Neurochemistry

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“…Neurofilament light chain protein is part of the neuronal cytoskeleton and increased levels in the CSF reflect axonal damage and degeneration 47 48. It is not disease-specific and has been used as a marker of neuronal injury in neurodegenerative disease,49 multiple sclerosis,47 cerebrovascular disease48 and traumatic brain injury 50. A recent study in patients with SLE and in patients with Sjögren’s syndrome reported increased CSF levels of neurofilament light chain protein in association with cognitive impairment 51.…”

Section: Discussionmentioning

confidence: 99%

“… 47 48 It is not disease-specific and has been used as a marker of neuronal injury in neurodegenerative disease, 49 multiple sclerosis, 47 cerebrovascular disease 48 and traumatic brain injury. 50 A recent study in patients with SLE and in patients with Sjögren’s syndrome reported increased CSF levels of neurofilament light chain protein in association with cognitive impairment. 51 Increased CSF levels of neurofilament light chain protein have also been reported in patients with SLE with other clinical NP manifestations.…”

Section: Discussionmentioning

confidence: 99%

Role of autoantibodies and blood–brain barrier leakage in cognitive impairment in systemic lupus erythematosus

et al. 2022

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ObjectiveCognitive impairment is common in patients with SLE but the cause is unknown. The current cross-sectional study examined the association between select SLE-related autoantibodies, other serological biomarkers and extensive blood–brain barrier (BBB) leakage in patients with SLE with and without cognitive impairment. In addition, we determined whether the relationship between SLE autoantibodies, other biomarkers and cognitive impairment differed depending on the presence or absence of concurrent extensive BBB leakage.MethodsConsecutive patients with SLE, recruited from a single academic medical centre, underwent formal neuropsychological testing for assessment of cognitive function. On the same day, BBB permeability was determined using dynamic contrast-enhanced MRI scanning. SLE autoantibodies and other serological biomarkers were measured. Regression modelling was used to determine the association between cognitive impairment, extensive BBB leakage and autoantibodies/biomarkers.ResultsThere were 102 patients with SLE; 90% were female and 88% were Caucasian, with a mean±SD age of 48.9±13.8 years. The mean±SD SLE disease duration was 14.8±11.0 years. Impairment in one or more cognitive tests was present in 47 of 101 (47%) patients and included deficits in information processing speed (9%), attention span (21%), new learning (8%), delayed recall (15%) and executive abilities (21%). Extensive BBB leakage was present in 20 of 79 (25%) patients and was associated with cognitive impairment (15 of 20 (75%) vs 24 of 59 (41%); p=0.01) and shorter disease duration (median (IQR): 7 (8–24 years) vs 15 (2–16 years); p=0.02). No serological parameters were associated with extensive BBB leakage and there was no statistically significant association between cognitive impairment and circulating autoantibodies even after adjusting for BBB leakage.ConclusionsExtensive BBB leakage alone was associated with cognitive impairment. These findings suggest that BBB leakage is an important contributor to cognitive impairment, regardless of circulating SLE-related autoantibodies.

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“…These age‐related changes are an important challenge when considering how to use the test clinically, resulting in the development of age‐specific cut‐points. It is also relevant that a number of common pathologies can elevate NfL, including mild traumatic brain injury, 37 cerebrovascular insults, 38 peripheral neuropathy 39 and kidney dysfunction, 40 all of which may need to be taken into account.…”

Section: Blood Biomarkers For Neurodegenerationmentioning

confidence: 99%