Neurofilament light chain concentration does not correlate with disease status in Labrador Retrievers affected with idiopathic laryngeal paralysis.

OBJECTIVE: The aim of this study was to investigate whether plasma neurofilament light chain (pNfL) concentration was altered in Labrador Retrievers with idiopathic laryngeal paralysis (ILP) compared to a control population. A secondary aim was to investigate relationships between age, height, weight, and body mass index in the populations studied. ANIMALS: 123 dogs: 62 purebred Labrador Retrievers with ILP (ILP Cases) and 61 age-matched healthy medium- to large-breed dogs (Controls). METHODS: Dogs, recruited from August 1, 2016, to March 1, 2022, were categorized as case or control based on a combination of physical exam, neurologic exam, and history. Blood plasma was collected, and pNfL concentration was measured. pNfL concentrations were compared between ILP Cases and Controls. Covariables including age, height, and weight were collected. Relationships between pNfL and covariables were analyzed within and between groups. In dogs where 2 plasma samples were available from differing time points, pNfL concentrations were measured to evaluate alterations over time. RESULTS: No significant difference in pNfL concentration was found between ILP Cases and Control (P = .36). pNfL concentrations had moderate negative correlations with weight and height in the Control group; other variables did not correlate with pNfL concentrations in ILP Case or Control groups. pNfL concentrations do not correlate with ILP disease status or duration in Labrador Retrievers. CLINICAL RELEVANCE: There is no evidence that pNfL levels are altered due to ILP disease duration or progression when compared with healthy controls. When evaluating pNfL concentrations in the dog, weight and height should be considered.

Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1-Associated Myelopathy and Correlates With Neuroinflammation.

BACKGROUND AND OBJECTIVES: To evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). METHODS: Nf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load. RESULTS: Nf-L was detected in all CSF samples (median [range] = 575 [791.8-2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = -0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF. CONCLUSIONS: Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.

Neurofilament light plasma concentration positively associates with age and negatively associates with weight and height in the dog.

Plasma neurofilament light chain (pNfL) concentration is a biomarker for neuroaxonal injury and degeneration and can be used to monitor response to treatment. Spontaneous canine neurodegenerative diseases are a valuable comparative resource for understanding similar human conditions and as large animal treatment models. The features of pNfL concentration in healthy dogs is not well established. We present data reporting basic pNfL concentration trends in the Labrador Retriever breed. Fifty-five Labrador Retrievers were enrolled. pNfL concentration was measured and correlated to age, sex, neuter status, height, weight, body mass index, and coat color. We found increased pNfL with age (P < 0.0001), shorter stature (P = 0.009) and decreased body weight (P < 0.001). These are similar to findings reported in humans. pNfL concentration did not correlate with sex, BMI or coat color. This data further supports findings that pNfL increase with age in a canine population but highlights a need to consider weight and height when determining normal pNfL concentration in canine populations.

Serum neurofilament light concentration does not increase following exposure to low velocity football heading.

Objectives: To investigate if heading frequency and impact biomechanics in a single session influence the concentration of serum neurofilament light (NF-L), a sensitive biomarker for axonal damage, up to 7 days after heading incident at ball velocities reflecting basic training drills.Methods: Forty-four males were randomized into either control (n = 8), 10 header (n = 12), 20 header (n = 12) or 40 header (n = 12) groups. Linear and angular head accelerations were quantified during heading. Venous blood samples were taken at baseline, 6 h, 24 h and 7 days after heading. Serum NF-L was quantified using Quanterix NF-L assay kit on the Simoa HD-1 Platform.Results: Serum NF-L did not alter over time (p = 0.44) and was not influenced by number of headers [p = 0.47; mean (95% CI) concentrations at baseline 6.00 pg · ml-1 (5.00-7.00 pg · ml-1); 6 h post 6.50 pg · ml-1 (5.70-7.29 pg · ml-1); 24 h post 6.07 pg · ml-1 (5.14-7.01 pg · ml-1); and 7 days post 6.46 pg · ml-1 (5.45-7.46 pg · ml-1)]. There was no relationship between percentage change in NF-L and summed session linear and angular head accelerations.Conclusion: In adult men, heading frequency or impact biomechanics did not affect NF-L response during a single session of headers at ball velocities reflective of basic training tasks.

Cerebrospinal fluid neurofilament light chain levels in CLN2 disease patients treated with enzyme replacement therapy normalise after two years on treatment.

Classic late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is caused by a deficiency of tripeptidyl-peptidase-1. In 2017, the first CLN2 enzyme replacement therapy (ERT) cerliponase alfa (Brineura) was approved by the FDA and EMA. The CLN2 disease clinical rating scale (CLN2 CRS) was developed to monitor loss of motor function, language and vision as well as frequency of generalised tonic clonic seizures. Using CLN2 CRS in an open label clinical trial it was shown that Brineura slowed down the progression of CLN2 symptoms. Neurofilament light chain (NfL) is a protein highly expressed in myelinated axons. An increase of cerebrospinal fluid (CSF) and blood NfL is found in a variety of neuroinflammatory, neurodegenerative, traumatic, and cerebrovascular diseases. We analysed CSF NfL in CLN2 patients treated with Brineura to establish whether it can be used as a possible biomarker of response to therapy. Newly diagnosed patients had CSF samples collected and analysed at first treatment dose and up to 12 weeks post-treatment to look at acute changes. Patients on a compassionate use programme who were already receiving ERT for approximately 1yr had CSF samples collected and NfL analysed over the following 1.3 years (2.3 years post-initiation of ERT) to look at long-term changes. All newly diagnosed patients we investigated with classical late infantile phenotype had high NfL levels >2000 pg/ml at start of treatment. No significant change was observed in NfL up to 12 weeks post-treatment. After one year of ERT, two out of six patients still had high NfL levels, but all patients showed a continued decrease, and all had low NfL levels after two years on ERT. NfL levels appear to correspond and predict improved clinical status of patients on ERT and could be useful as a biomarker to monitor neurodegeneration and verify disease modification in CLN2 patients on ERT.