CSF-NFL Levels Research Articles

Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis.

Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection.

It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury. Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance. Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04). CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health.

D07 Levels Of The Light Subunit Of Neurofilatment Protein In Cerebrospinal Fluid In Huntington's Disease

Introduction Light subunit of neurofilament protein (NFL) is a structural element of neurons. Its levels are increased in cerebrospinal fluid (CSF) in the setting of neurological diseases, including Huntington’s disease (HD), and are considered a marker of neuronal damage. HD is a paradigm of neurodegeneration in the need of appropriate biomarkers. Objectives To compare the levels of CSF-NFL of HD patients and healthy controls. To correlate CSF-NFL levels with demographic and clinical variables. Methods The ELISA for NFL was performed according to previously published methods. Twenty-four HD participants (11 women; mean age 47.3 (SD 12.3)) and 37 controls (26 women; mean age 34.1 (SD 9.4)) were included. We compared levels of NFL-CSF levels with a regression model adjusted for age and gender. We examined the relationships (Pearson correlations) between NFL-CSF levels and demographic (age, gender) and clinical (CAG repeat number, disease burden, UHDRS motor, behavioural, functional total scores and NPI scale) variables. Results CSF levels were significantly higher in all HD subjects [5014.4 (1557.3) ng/l] as compared to controls [335.4 (193.3) ng/l] (p Conclusions These results indicate that NFL-CSF levels is a marker of neuronal damage in HD and warrant future efforts towards establishing its sensitivity to track disease progression and reactivity to therapeutical interventions.

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson’s disease

Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non-specific marker of neuronal damage, are normal in Parkinson's disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF-NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. CSF-NFL levels were measured consecutively in eight patients with PD before and after STN-DBS treatment. CSF-NFL levels were normal prior to STN-DBS and increased sharply during the first 2 weeks post-operatively, but normalized after 12 months or more. The STN-DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF-NFL levels at 12 months post-operatively and beyond suggest the absence of any long-term neuronal damage caused by long-term STN-DBS stimulation.

Cerebrospinal fluid biomarkers of white matter lesions – cross‐sectional results from the LADIS study

White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.

CSF neurofilament proteins in the differential diagnosis of dementia

Background: Neurofilament (NF) proteins are major cytoskeletal constituents of neurons. Increased CSF NF levels may reflect neuronal degeneration. Objective: To investigate the diagnostic value of CSF NF analysis to discriminate...

Pathophysiological aspects of frontotemporal dementia—emphasis on cytoskeleton proteins and autoimmunity

The aim of this study was to investigate two putative pathophysiological aspects of the common neurodegenerative disorder frontotemporal dementia (FTD). To this end, cerebrospinal fluid (CSF) levels of tau (total tau) and the light subtype of the neurofilament proteins (NFL) were studied in patients with FTD ( n=16) and in age-matched controls ( n=16). In addition, serum was analysed for IgG and IgM antibodies to the most common gangliosides and sulfatide in FTD patients ( n=13) and in age-matched controls ( n=20). The CSF-NFL levels were increased in FTD (1606±1151 pg/ml, mean±S.D.; P<0.001) compared with controls (308±203 pg/ml), whereas the CSF-tau levels were normal. In serum, autoantibody IgG-GA1 was significantly increased in FTD ( P<0.05) compared with controls. No correlations were found between the effect parameters and demographic variables in any group. The results of this study suggest that cytoskeleton proteins other than tau are also involved in the pathophysiology of FTD and that autoimmunity may be part of the pathophysiological processes in FTD, as it is believed to be in Alzheimer's disease.

Cytoskeleton proteins in CSF distinguish frontotemporal dementia from AD.

To investigate the CSF levels of tau and the light neurofilament protein (NFL) in patients with frontotemporal dementia (FTD) and other common dementia disorders as well as normal control subjects. Both proteins have been implicated in the pathophysiology of FTD. CSF levels of tau and NFL were investigated in 18 patients with FTD, 21 patients with early-onset AD (EAD), 21 patients with late-onset AD (LAD), and 18 age-matched control subjects. Mean +/- SD CSF NFL levels were increased in patients with FTD (1442 +/- 1183 pg/mL; p < 0.05) and LAD (1006 +/- 727 pg/mL; p < 0.001) compared with control subjects (241 +/- 166 pg/mL) and in LAD compared with EAD (498 +/- 236 pg/mL; p < 0.05), and tended to be increased in FTD compared with EAD. CSF tau levels were increased in EAD (751 +/- 394 pg/mL; p < 0.01) and LAD (699 +/- 319 pg/mL; p < 0.01) compared with control subjects (375 +/- 170 pg/mL), and in EAD (p < 0.001) and LAD (p < 0. 01) compared with FTD (354 +/- 140 pg/mL). CSF NFL correlated positively with degree of cognitive impairment in FTD (r = 0.59; p < 0.05) and LAD (r = 0.61; p < 0.01). No significant differences were found in CSF NFL or CSF tau when comparing patients who did and did not possess the APOE-epsilon4 allele within each diagnostic group. The results suggest a differential involvement of these cytoskeleton proteins in FTD and EAD, with NFL primarily involved in the pathophysiology of FTD and tau in that of EAD. The increase in CSF NFL found in LAD might reflect the white-matter degeneration found in a proportion of LAD cases.

Frontotemporal dementia - Clinical and pathophysiological aspects

"Frontotemporal dementia - Clinical and pathophysiological aspects." Nordic Journal of Psychiatry, 54(2), pp. 149–150

Neurofilament protein levels in CSF are increased in dementia.

The neurofilament is the major cytoskeletal structure of myelinated axons. In this study, CSF levels of the light subunit of the neurofilament protein (NFL) were increased in patients with vascular dementia (VAD), AD, and frontotemporal dementia (FTD) compared with neurologically healthy individuals. Because NFL is localized mainly in myelinated axons, these results suggest that the degeneration of white matter in these disorders causes the increased CSF NFL levels.

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<h3>Objective</h3> To assess the role of CSF chitinase 3-like-1 (CHI3L1), chitinase 3-like-2 (CHI3L2), and neurofilament light chain (NfL) in predicting the course of primary progressive MS (PPMS). <h3>Methods</h3> We analyzed CSF CHI3L1, CHI3L2, and NfL levels in 25 patients with PPMS with disease duration ≤10 years and no disease-modifying therapy for ≥6 months from the prospective Understanding Primary Progressive Multiple Sclerosis cohort study. CSF samples taken at disease diagnosis were analyzed using commercial ELISAs and following the manufacturer9s instructions. Data on Expanded Disability Status Scale (EDSS) scores, disability progression, and cognitive function according to the Brief Repeatable Neuropsychological Battery were also assessed throughout the 1-year study follow-up. <h3>Results</h3> Increasing CHI3L1 levels correlated with higher EDSS scores at baseline (ρ = 0.490, 95% CI 0.118–0.742, <i>p</i> = 0.013) and month 12 (ρ = 0.455, 95% CI 0.063–0.725, <i>p</i> = 0.026) and tended to be associated with a higher risk of disability progression according to EDSS scores (OR = 1.008, 95% CI 0.999–1.017, <i>p</i> = 0.089). Increasing CHI3L2 levels also tended to correlate with lower baseline EDSS scores (ρ = −0.366, 95% CI -0.676–0.054, <i>p</i> = 0.086). There was no correlation with regard to NfL levels. <h3>Conclusions</h3> This analysis supports the association between CSF CHI3L1 levels and neurologic disability according to EDSS scores in patients with PPMS. Other chitinase-like proteins such as CHI3L2 may also be involved. <h3>Classification of evidence</h3> This study provides Class II evidence that CSF CHI3L1 is associated with neurologic disability in patients with PPMS.