Serum Neurofilament Light Chain Levels Research Articles

Dietary creatine is associated with lower serum neurofilament light chain levels.

Low creatine availability may be linked to an elevated risk of neuronal damage, yet this association remains inadequately explored at the population level. Utilizing 2013-2014 National Health and Nutrition Examination Survey data, the current study found a negative correlation between dietary creatine intake and serum levels of neurofilament light chain (NfL; a biomarker for neuronal damage) in a cohort of 1912 individuals (52.2% females) aged 20-75 years. This inverse association persisted even after adjusting for other nutritional variables known to influence neuronal viability. The observed pattern, where increased dietary creatine intake was associated with reduced circulating NfL levels, suggests potential protective effects of creatine against neuronal injury.

Altered cerebrospinal fluid neurofilament light chain but not neurogranin levels are associated with response to ocrelizumab treatment in relapsing remitting multiple sclerosis: a preliminary study.

Ocrelizumab is a CD20-targeting monoclonal antibody used for treatment of multiple sclerosis (MS). Serum and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels are reduced in MS patients under ocrelizumab treatment indicating a preventive action against neuro-axonal degeneration. Our aim, in this preliminary study, was to explore the impact of ocrelizumab treatment on synaptic integrity through assessment of neurogranin levels. Thirteen relapsing-remitting multiple sclerosis (RRMS) patients resistant to first-line immunomodulating agents were enrolled and followed up for 24 months under ocrelizumab treatment. Disease activity was monitored by periodic EDSS, MSSS and cranial-spinal MRI assessments. No evidence of disease (NEDA)-3 activity was determined and CSF levels of NFL (marker of neuro-axonal integrity) and neurogranin (marker of synaptic integrity) were measured by ELISA at baseline and 12-month ocrelizumab treatment. Seven RRMS patients, who preserved NEDA-3 status during 24-month follow-up showed ≥30% NFL level decrease, whereas six patients with stable/increased NFL levels displayed relapse, MRI lesion or disability progression. Although most RRMS patients exhibited increased CSF levels of neurogranin under ocrelizumab treatment, patients with and without neurogranin level increase did not differ in terms of clinical features and NEDA-3 status. Baseline neurogranin levels negatively correlated with baseline EDSS scores. Our results confirm that NFL effectively monitors treatment response of RRMS patients under ocrelizumab treatment. Neurogranin does not appear to exhibit a similar benefit in screening of RRMS disease activity. Nevertheless, lower neurogranin levels are associated with increased disability in RRMS indicating a potential disease activity biomarker function.

Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis.

Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.

Serum neurofilament light chain levels correlate with small fiber related parameters in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

Recent evidence suggests that both serum neurofilament light chain (sNfL) levels and small fiber related diagnostic variables may be valuable disease biomarkers of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). Our study aimed to explore the relations between sNfL and small fiber related skin biopsy and quantitative sensory testing (QST) parameters in a cohort of ATTRv-PN patients and pre-symptomatic carriers. We retrospectively analyzed data from 13 ATTRv patients and 21 pre-symptomatic carriers who underwent sNfL dosage, skin biopsy, and QST, and analyzed correlations between sNFL, intraepidermal nerve fiber density (IENFD), and cold (CDT) and warm detection thresholds (WDT). Both sNfL and small fiber related parameters significantly differed between carriers and patients (sNfL: p < 0.0001; IENFD: p = 0.0008; CDT, WDT: < 0.0001). sNFL levels were normal in all carriers, altered in 85% of patients, negatively correlated with distal IENFD (r = -0.47, p = 0.005), and significantly correlated with CDT (r = -0.68; p < 0.0001) and WDT (r = 0.57; p < 0.0001). Our study showed that sNfL reliably discriminates symptomatic ATTRv-PN patients from pre-symptomatic carriers, and found significant relations between sNfL, skin biopsy, and QST small fiber related parameters, suggesting that sNfL might be a valuable biomarker of peripheral nerve involvement in ATTRv-PN and a supportive criterion for symptomatic disease transition.

Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.

Associations of sleep disorders with serum neurofilament light chain levels in Parkinson’s disease

BackgroundSleep disorders are a prevalent non-motor symptom of Parkinson’s disease (PD), although reliable biological markers are presently lacking.ObjectivesTo explore the associations between sleep disorders and serum neurofilament light chain (NfL) levels in individuals with prodromal and early PD.MethodsThe study contained 1113 participants, including 585 early PD individuals, 353 prodromal PD individuals, and 175 healthy controls (HCs). The correlations between sleep disorders (including rapid eye movement sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS)) and serum NfL levels were researched using multiple linear regression models and linear mixed-effects models. We further investigated the correlations between the rates of changes in daytime sleepiness and serum NfL levels using multiple linear regression models.ResultsIn baseline analysis, early and prodromal PD individuals who manifested specific behaviors of RBD showed significantly higher levels of serum NfL. Specifically, early PD individuals who experienced nocturnal dream behaviors (β = 0.033; P = 0.042) and movements of arms or legs during sleep (β = 0.027; P = 0.049) showed significantly higher serum NfL levels. For prodromal PD individuals, serum NfL levels were significantly higher in individuals suffering from disturbed sleep (β = 0.038; P = 0.026). Our longitudinal findings support these baseline associations. Serum NfL levels showed an upward trend in early PD individuals who had a higher total RBDSQ score (β = 0.002; P = 0.011) or who were considered as probable RBD (β = 0.012; P = 0.009) or who exhibited behaviors on several sub-items of the RBDSQ. In addition, early PD individuals who had a high total ESS score (β = 0.001; P = 0.012) or who were regarded to have EDS (β = 0.013; P = 0.007) or who exhibited daytime sleepiness in several conditions had a trend toward higher serum NfL levels.ConclusionSleep disorders correlate with higher serum NfL, suggesting a link to PD neuronal damage. Early identification of sleep disorders and NfL monitoring are pivotal in detecting at-risk PD patients promptly, allowing for timely intervention. Regular monitoring of NfL levels holds promise for tracking both sleep disorders and disease progression, potentially emerging as a biomarker for evaluating treatment outcomes.

Association between sleep duration and serum neurofilament light chain levels among adults in the United States

BackgroundNeurofilaments are neuron specific skeleton proteins maintaining axon transduction speed, leaked into cerebrospinal fluid and serum after axonal injury or neuron death. Sleep duration change has long related to many health issues but lack laboratory examination. MethodsThis study enrolled total 10,175 participants from 2013 to 2014 National Health and Nutrition Examination Survey and used a multi-variable linear model to analyze the relationship between sleep duration and serum neurofilament light chain (sNfL) level. ResultsThere was a fixed relationship between sleep duration and sNfL level (β = 0.65, p = 0.0280). After adjusted for covariates, this relationship still (β = 0.82, p = 0.0052). Segmented regression showed that the turning point of sleep duration was 7 h 1 h decrease in sleep duration was significantly associated with −1.26 higher sNfL level (95 % CI: 2.25, −0.28; p = 0.0115) when sleep duration <7 h; however, 1 h increase in sleep duration was significantly associated with 3.20 higher sNfL level (95 % CI: 2.13, 4.27; p < 0.0001) when sleep duration >7 h. Furthermore, the stratified analysis indicated that the associations between sleep duration and sNfL level were stronger among those normal body mass index and trouble sleeping (p-interaction <0.0001 and 0.0003). ConclusionIn summary, there was a J-shaped relationship between sleep duration and sNfL level in the United States of America representative group, these may suggest that extreme sleep duration can be deleterious judged by sNfL level. And still need large cohort study to determine the accurate relationship, and cluster analysis to infer the nervous disease connected with extreme sleep duration.

Serum and cerebrospinal fluid neurofilament light chain and glial fibrillary acid protein levels in early and advanced stages of cerebral amyloid Angiopathy

BackgroundNeurofilament light chain (NFL) is a biomarker for neuroaxonal damage and glial fibrillary acidic protein (GFAP) for reactive astrocytosis. Both processes occur in cerebral amyloid angiopathy (CAA), but studies investigating the potential of NFL and GFAP as markers for CAA are lacking.We aimed to investigate NFL and GFAP as biomarkers for neuroaxonal damage and astrocytosis in CAA.MethodsFor this cross-sectional study serum and cerebrospinal fluid (CSF) samples were collected between 2010 and 2020 from controls, (pre)symptomatic Dutch-type hereditary (D-CAA) mutation-carriers and participants with sporadic CAA (sCAA) from two prospective CAA studies at two University hospitals in the Netherlands. NFL and GFAP levels were measured with Simoa-assays. The association between NFL and GFAP levels and age, cognitive performance (MoCA), CAA-related MRI markers (CAA-CSVD-burden) and Aβ40 and Aβ42 levels in CSF were assessed with linear regression adjusted for confounders. The control group was divided in age < 55 and ≥55 years to match the specific groups.ResultsWe included 187 participants: 28 presymptomatic D-CAA mutation-carriers (mean age 40 years), 29 symptomatic D-CAA participants (mean age 58 years), 59 sCAA participants (mean age 72 years), 33 controls < 55 years (mean age 42 years) and 38 controls ≥ 55 years (mean age 65 years).In presymptomatic D-CAA, only GFAP in CSF (7.7*103pg/mL vs. 4.4*103pg/mL in controls; P<.001) was increased compared to controls. In symptomatic D-CAA, both serum (NFL:26.2pg/mL vs. 12.5pg/mL; P=0.008, GFAP:130.8pg/mL vs. 123.4pg/mL; P=0.027) and CSF (NFL:16.8*102pg/mL vs. 7.8*102pg/mL; P=0.01 and GFAP:11.4*103pg/mL vs. 7.5*103pg/mL; P<.001) levels were higher than in controls and serum levels (NFL:26.2pg/mL vs. 6.7pg/mL; P=0.05 and GFAP:130.8pg/mL vs. 66.0pg/mL; P=0.004) were higher than in pre-symptomatic D-CAA. In sCAA, only NFL levels were increased compared to controls in both serum (25.6pg/mL vs. 12.5pg/mL; P=0.005) and CSF (20.0*102pg/mL vs 7.8*102pg/mL; P=0.008). All levels correlated with age. Serum NFL correlated with MoCA (P=0.008) and CAA-CSVD score (P<.001). NFL and GFAP in CSF correlated with Aβ42 levels (P=0.01/0.02).ConclusionsGFAP level in CSF is an early biomarker for CAA and is increased years before symptom onset. NFL and GFAP levels in serum and CSF are biomarkers for advanced CAA.

Serum neurofilament light chain and inflammatory cytokines as biomarkers for early detection of mild cognitive impairment

To investigate the association between serum neurofilament light chain (NfL) levels, inflammatory cytokines, and cognitive function to assess their utility in the early detection of mild cognitive impairment (MCI). We conducted a cross-sectional study involving 157 community-dwelling individuals aged 55 years and above, categorized into healthy controls, MCI, and probable Alzheimer's disease (AD). Serum levels of NfL, inflammatory cytokines, and AD pathology markers were measured using enzyme-linked immunosorbent assay (ELISA). Correlations between these biomarkers and cognitive function were analyzed, and the diagnostic performance of the cognitive assessment scales and serum biomarker concentrations was evaluated using receiver operating characteristic (ROC) curve analysis. Serum NfL levels were significantly elevated in MCI and probable AD groups compared to healthy controls. Positive correlations were found between serum NfL and inflammatory cytokines IL-1β, IL-6, and Aβ40. Combining serum NfL with p-tau217 and the Boston Naming Test significantly enhanced the predictive accuracy for MCI. However, combining serum NfL with inflammatory markers did not improve MCI prediction accuracy. Elevated serum NfL is associated with cognitive impairment and inflammatory markers, suggesting its potential as a peripheral serum biomarker for MCI detection. The combination of serum NfL with p-tau217 and cognitive tests could offer a more accurate prediction of MCI, providing new insights for AD treatment strategies.

Serum neurofilament light chain levels as multiple sclerosis biomarker

Serum neurofilament light chain levels as multiple sclerosis biomarker

Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving rapid motor neuron degeneration leading to brain, primarily precentral, atrophy. Neurofilament light chains are a robust prognostic biomarker highly specific to ALS, yet associations between neurofilament light chains and MR imaging outcomes are not well-understood. We investigated the role of neurofilament light chains as mediators among neuroradiologic assessments, precentral neurodegeneration, and disability in ALS. We retrospectively analyzed a prospective cohort of 29 patients with ALS (mean age, 56 [SD, 12] years; 18 men) and 36 controls (mean age, 49 [SD, 11] years; 18 men). Patients underwent 3T (n = 19) or 7T (n = 10) MR imaging, serum (n = 23) and CSF (n = 15) neurofilament light chains, and clinical (n = 29) and electrophysiologic (n = 27) assessments. The control group had equivalent 3T (n = 25) or 7T (n = 11) MR imaging. Two trained neuroradiologists performed blinded qualitative assessments of MR imaging anomalies (n = 29 patients, n = 36 controls). Associations between precentral cortical thickness and neurofilament light chains and clinical and electrophysiologic data were analyzed. We observed extensive cortical thinning in patients compared with controls. MR imaging analyses showed significant associations between precentral cortical thickness and bulbar or arm impairment following distributions corresponding to the motor homunculus. Finally, uncorrected results showed positive interactions among precentral cortical thickness, serum neurofilament light chains, and electrophysiologic outcomes. Qualitative MR imaging anomalies including global atrophy (P = .003) and FLAIR corticospinal tract hypersignal anomalies (P = .033), correlated positively with serum neurofilament light chains. Serum neurofilament light chains may be an important mediator between clinical symptoms and neuronal loss according to cortical thickness. Furthermore, MR imaging anomalies might have underestimated prognostic value because they seem to indicate higher serum neurofilament light chain levels.

Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis

Objective To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and TTR variant (TTRv) carriers. Methods sNfL levels were assessed longitudinally in persistently asymptomatic TTRv carriers (N = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (N = 8), in TTRv carriers who developed polyneuropathy (N = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (N = 20) or TTR-silencer (N = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay. Results sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic TTRv carriers. In all TTRv carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment. Conclusion sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic TTRv carriers and in monitoring of disease progression and treatment effect.

The association of menopausal hormone levels with progression-related biomarkers in multiple sclerosis

BackgroundMultiple sclerosis (MS) progression coincides temporally with menopause. However, it remains unclear whether the changes in disease course are related to the changes in reproductive hormone concentrations. We assessed the association of menopausal hormonal levels with progression-related biomarkers of MS and evaluated the changes in serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels during menopausal hormone therapy (MHT) in a prospective baseline-controlled design. MethodsThe baseline serum estradiol, follicle stimulating hormone, and luteinizing hormone levels were measured from menopausal women with MS (n = 16) and healthy controls (HC, n = 15). SNfL and sGFAP were measured by single-molecule array. The associations of hormone levels with sNfL and sGFAP, and with Expanded Disability Status Scale (EDSS) and lesion load and whole brain volumes (WBV) in MRI were analyzed with Spearman's rank correlation and age-adjusted linear regression model. Changes in sNfL and sGFAP during one-year treatment with estradiol hemihydrate combined with cyclic dydrogesterone were assessed with Wilcoxon Signed Ranks Test. ResultsIn MS group, baseline estradiol had a positive correlation with WBV in MRI and an inverse correlation with lesion load, sNfL and sGFAP, but no correlation with EDSS. The associations of low estradiol with high sGFAP and low WBV were independent of age. During MHT, there was no significant change in sNfL and sGFAP levels in MS group while in HC, sGFAP slightly decreased at three months but returned to baseline at 12 months. ConclusionOur preliminary findings suggest that low estradiol in menopausal women with MS has an age-independent association with more pronounced brain atrophy and higher sGFAP and thus advanced astrogliosis which could partially explain the more rapid progression of MS after menopause. One year of MHT did not alter the sGFAP or sNfL levels in women with MS.

Neurofilament light-chain (NfL) and 18 kDa translocator protein in early psychosis and its putative high-risk

Evidence of elevated peripheral Neurofilament light-chain (NfL) as a biomarker of neuronal injury can be utilized to reveal nonspecific axonal damage, which could reflect altered neuroimmune function. To date, only a few studies have investigated NfL as a fluid biomarker in schizophrenia primarily, though none in its putative prodrome (Clinical High-Risk, CHR) or in untreated first-episode psychosis (FEP). Further, it is unknown whether peripheral NfL is associated with 18 kDa translocator protein (TSPO), a validated neuroimmune marker. In this secondary study, we investigated for the first time (1) serum NfL in early stages of psychosis including CHR and FEP as compared to healthy controls, and (2) examined its association with brain TSPO, using [18F]FEPPA positron emission tomography (PET). Further, in the exploratory analyses, we aimed to assess associations between serum NfL and symptom severity in patient group and cognitive impairment in the combined cohort. A large cohort of 84 participants including 27 FEP (24 antipsychotic-naive), 41 CHR (34 antipsychotic-naive) and 16 healthy controls underwent structural brain MRI and [18F]FEPPA PET scan and their blood samples were obtained and assessed for serum NfL concentrations. We found no significant differences in serum NfL levels across clinical groups, controlling for age. We also found no significant association between NfL levels and brain TSPO in the entire cohort. We observed a negative association between serum NfL and negative symptom severity in CHR. Our findings suggest that neither active neuroaxonal deterioration as measured with NfL nor associated neuroimmune activation (TSPO) is clearly identifiable in an early mostly untreated psychosis sample including its putative high-risk.

Predictive value of individual serum neurofilament light chain levels in short-term disease activity in relapsing multiple sclerosis.

The assessment of serum neurofilament light chain (sNFL) has emerged as a diagnostic and prognostic tool in monitoring multiple sclerosis (MS). However, the application of periodic measurement in daily practice remains unclear. To evaluate the predictive value of individual sNFL levels in determining disease activity in patients with relapsing MS (RMS). In this two-year prospective study, 129 RMS patients underwent quarterly sNFL assessments and annual MRI scans. The study analyzed the correlation between individual NFL levels and past, current, and future disease activity. Group-level Z-scores were employed as a comparative measure. Among the 37 participants, a total of 61 episodes of disease activity were observed. sNFL levels proved valuable in distinct ways; they were confirmatory of previous and current clinical and/or radiological activity and demonstrated a high negative predictive value for future 90 days activity. Interestingly, Z-scores marginally outperformed sNFL levels in terms of predictive accuracy, indicating the potential for alternative approaches in disease activity assessment. In our cohort, sNFL cut-offs of 10.8 pg./mL (sensitivity 27%, specificity 90%) and 14.3 pg./mL (sensitivity 15%, specificity 95%) correctly identified 7 and 4 out of 26 cases of radiological activity within 90 days, respectively, with 14 and 15% false negatives. When using lower cut-off values, individuals with sNFL levels below 5 pg/mL (with a sensitivity of 92%, specificity of 25%, and negative predictive value of 94%) were less likely to experience radiological activity within the next 3 months. Individual sNFL levels may potentially confirm prior or current disease activity and predict short-term future radiological activity in RMS. These findings underscore its periodic measurement as a valuable tool in RMS management and decision-making, enhancing the precision of clinical evaluation in routine practice.

Effects of obstructive sleep apnea treatment on neurodegenerative biomarker neurofilament light chain and cognitive performance.

Obstructive sleep apnea is associated with cognitive impairment and increased risk for neurodegenerative diseases. Obstructive sleep apnea treatment with positive airway pressure therapy helps to improve cognitive symptoms and reduces long-term dementia risk. To test whether these treatment effects are due to a reduction in neuronal damage, we examined longitudinal changes in the neurodegenerative serum neurofilament light chain and cognitive performance of patients with obstructive sleep apnea. In this study, 17 patients with obstructive sleep apnea completed baseline and follow-up (9 month after starting PAP treatment) investigation of sleep, daytime symptoms, cognitive testing and serum neurofilament light chain measurements. Depending on treatment adherence and efficacy, participants were assigned either to the effective treatment (n = 10) or non-effective treatment group (n = 7). As results at baseline lower mean oxygen saturation during sleep was associated with higher serum neurofilament light chain. Patients in the non-effective treatment group showed a significant increase of age-adjusted percentile of serum neurofilament light chain levels at follow-up, whereas serum neurofilament light chain values remained constant in the effective treatment group. At a functional level, effective treatment leads to an improvement in processing speed, which was not the case in the non-effective treatment group. Longitudinal changes of age-adjusted serum neurofilament light chain levels were associated with changes in cognitive performance. To conclude, this longitudinal observational study showed that effective obstructive sleep apnea treatment positively affects the amount of neuronal damage as well as working memory performance. As cognitive symptoms might not only be attributed to obstructive sleep apnea-related sleep deficiency, but also neurodegeneration, our results underline the importance of treatment adherence and efficacy for the prevention of neuronal damage and cognitive consequences.

Relationship between increased serum neurofilament light chain and glial fibrillary acidic protein levels with non-motor symptoms in patients with Parkinson's disease.

This study set out to investigate the relationship between serum neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and various non-motor symptoms (NMSs) in patients with Parkinson's disease (PD). The study included 37 healthy controls (HCs) and 51 PD patients. Clinical assessments of PD symptoms were conducted for all PD patients. The NMSS was utilised to evaluate the NMS burden (NMSB) in individuals. Based on the severity of NMSB, we further categorised the PD group into two subgroups: mild-moderate NMSB group and severe-very severe NMSB group. The amounts of NFL and GFAP in the serum were measured using an extremely sensitive single molecule array (Simoa) method. Statistical analyses were performed on the collected data using SPSS 26.0 and R (version 3.6.3). Serum GFAP and NFL levels in the PD group with severe-very severe NMSB were significantly higher than those in the mild-moderate NMSB group (GFAP: P < 0.007; NFL: P < 0.009). Serum NFL and GFAP levels had positive correlations with NMSS total scores (GFAP: r = 0.326, P = 0.020; NFL: r = 0.318, P = 0.023) and multiple subdomains. The relationship between the attention/memory domains of NMSS and NFL levels is significantly positive (r = 0.283, P = 0.044). Similarly, the mood/apathy domains of NMSS are also significantly positively correlated with GFAP levels (r = 0.441, P = 0.001). Patients with emotional problems or cognitive impairment had higher GFAP or NFL levels, respectively. Furthermore, it has been demonstrated that NMSs play a mediating role in the quality of life of patients with PD. Moreover, the combination of NFL and GFAP has proven to be more effective than using a single component in identifying PD patients with severe-very severe NMSB. The severity of NMSs in PD patients, particularly cognitive and emotional symptoms, was found to be associated with the levels of serum NFL and GFAP. This study marks the first attempt to examine the connection between NMSs of PD and the simultaneous identification of NFL and GFAP levels.

Serum Neurofilament and Free Light Chain Levels in Patients Undergoing Treatment for Chronic Inflammatory Demyelinating Polyneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nervous system. Despite the established diagnostic criteria, monitoring disease activity and treatment remains challenging. To address this limitation, we investigated serum neurofilament light chain (sNfL) and serum free light chains (sFLCs) as potential biomarkers. A total of 32 CIDP patients undergoing immunoglobulin therapy and 32 healthy controls enrolled in the present study, and agreed to have their blood plasma sNfL and sFLCs analyzed, while CIDP severity was assessed through the modified Rankin Scale (mRS) and the Overall Neuropathy Limitations Scale (ONLS). In line with the immunoglobulin treatment aimed at limiting neuronal damage administered to the majority of patients, sNfL levels did not exhibit significant differences between the two groups. However, CIDP patients showed significantly elevated sFLC and sFLC ratios, while the marker levels did not correlate with the clinical scores. The study confirms the potential of sFLCs as a sensitive biomarker of inflammatory processes in CIDP. Additionally, the present study results regarding neurofilaments strengthen the role of sNfL in monitoring CIDP treatments, confirming the effectiveness of immunoglobulin therapy. Overall, our results demonstrate how combining these markers can lead to better patient characterization for improved treatment.

Studying serum neurofilament light chain levels as a potential new biomarker for small fiber neuropathy.

Diagnosing small fiber neuropathies can be challenging. To address this issue, whether serum neurofilament light chain (sNfL) could serve as a potential biomarker of damage to epidermal Aδ- and C-fibers was tested. Serum NfL levels were assessed in 30 patients diagnosed with small fiber neuropathy and were compared to a control group of 19 healthy individuals. Electrophysiological studies, quantitative sensory testing and quantification of intraepidermal nerve fiber density after skin biopsy were performed in both the proximal and distal leg. Serum NfL levels were not increased in patients with small fiber neuropathy compared to healthy controls (9.1 ± 3.9 and 9.4 ± 3.8, p = 0.83) and did not correlate with intraepidermal nerve fiber density at the lateral calf or lateral thigh or with other parameters of small fiber impairment. Serum NfL levels cannot serve as a biomarker for small fiber damage.

Evaluation of Serum Neurofilament Light Chain and Nerve Ultrasound in Diabetic Neuropathy.

To assess the role of serum neurofilament light chain (NfL) levels in individuals with diabetic polyneuropathy (DPN) compared with controls, as well as to highlight the different sonographic changes in DPN and determine if NfL correlates with sonographic, clinical, and functional parameters. Diabetic individuals with signs or symptoms consistent with peripheral nerve involvement were recruited. They were evaluated by examination, functional neuropathy severity scores, laboratory assessments (including NfL), nerve conduction studies (NCS), and ultrasound. Ultrasound was performed of the bilateral median, ulnar, tibial, fibular, sural, and vagus nerves, and cervical roots 5 and 6. Results were compared with age, sex, and body mass index matched healthy controls. A total of 320 nerves from 20 patients and 480 nerves from 30 controls were evaluated. NfL was significantly elevated in those with diabetes with a mean and standard deviation of 6.95 ± 2.95 pg/mL in the diabetic group and 2.83 ± 0.77 pg/mL in controls (P < .001). Nerve cross-sectional area and serum NfL levels correlated significantly with clinical and functional parameters and with each other (P < .05). Individuals with DPN have significantly higher NfL levels than healthy controls, and NfL levels correlate with ultrasonographic parameters. These findings may be useful for the diagnosis, prognosis, and disease monitoring of those with DPN, though further exploration is needed.