BACKGROUND: Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA.
METHODS: GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson\'s disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores).
RESULTS: In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90-1.00; plasma: AUC = 0.90, 95% CI 0.81-1.00).
CONCLUSIONS: In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.

BACKGROUND: Frontotemporal dementia (FTD) is characterized by phenotypic and genetic heterogeneities. However, reports on the large Chinese FTD cohort are lacking.
METHODS: Two hundred forty-eight patients with FTD were enrolled. All patients and 2010 healthy controls underwent next generation sequencing. Plasma samples were analyzed for glial fibrillary acidic protein (GFAP), α-synuclein (α-syn), neurofilament light chain (NfL), and phosphorylated tau protein 181 (p-tau181).
RESULTS: Gene sequencing identified 48 pathogenic or likely pathogenic mutations in a total of 19.4% of patients with FTD (48/248). The most common mutation was the C9orf72 dynamic mutation (5.2%, 13/248). Significantly increased levels of GFAP, α-syn, NfL, and p-tau181 were detected in patients compared to controls (all p < 0.05). GFAP and α-syn presented better performance for diagnosing FTD.
CONCLUSIONS: We investigated the characteristics of phenotypic and genetic spectrum in a large Chinese FTD cohort, and highlighted the utility of plasma biomarkers for diagnosing FTD.
CONCLUSIONS: This study used a frontotemporal dementia (FTD) cohort with a large sample size in Asia to update and reveal the clinical and genetic spectrum, and explore the relationship between multiple plasma biomarkers and FTD phenotypes as well as genotypes. We found for the first time that the C9orf72 dynamic mutation frequency ranks first among all mutations, which broke the previous impression that it was rare in Asian patients. Notably, it was the first time the C9orf72 G4C2 repeat expansion had been identified via whole-genome sequencing data, and this was verified using triplet repeat primed polymerase chain reaction (TP-PCR). We analyzed the diagnostic accuracy of four plasma biomarkers (glial fibrillary acidic protein [GFAP], α-synuclein [α-syn], neurofilament light chain [NfL], and phosphorylated tau protein 181 [p-tau181]) at the same time, especially for α-syn being included in the FTD cohort for the first time, and found GFAP and α-syn had the highest diagnostic accuracy for FTD and its varied subtypes.

BACKGROUND: The prognostic role of plasma neurofilament light chain (NfL), phospho-tau, beta-amyloid, and GFAP is still debated in Parkinson\'s disease (PD).
METHODS: Plasma p-tau181, p-tau231, Aβ1-40, Aβ1-42, GFAP, and NfL were measured by SIMOA in 136 PD with 2.9 + 1.7 years of follow-up and 76 controls. Differences in plasma levels between controls and PD and their correlation with clinical severity and progression rates were evaluated using linear regression analyses.
RESULTS: Patients exhibited similar distribution of plasma biomarkers but higher P-tau181, P-tau231 and lower Aβ1-42 compared with controls. NfL and GFAP correlated with baseline motor and non-motor severity measures. At follow-up, NfL emerged as the best predictor of progression with marginal effect of GFAP and p-tau181 adjusting for age, sex, disease duration, and baseline motor severity.
CONCLUSIONS: The present findings confirmed plasma NfL as best predictor of progression in PD, with a marginal role of p-tau181 and GFAP.

BACKGROUND: Elevated neurofilament light chain (NfL) levels are associated with worse prognosis in Guillain-Barré syndrome (GBS). Our objectives were to determine the utility of serum NfL (sNfL), cerebrospinal fluid (CSF)/serum NfL ratio and NfL index as prognostic and diagnostic biomarkers for GBS.
METHODS: We measured NfL in serum and/or CSF obtained from 96 GBS patients between 1989 and 2014 in western Sweden. The sNfL Z-scores, NfL ratios and NfL indices were calculated. Outcome was determined with the GBS disability scale (GBSDS) at 3 and 12 months. NfL parameters in GBS were compared with healthy controls (HC), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS).
RESULTS: The sNfL Z-score was higher for GBSDS > 2 at 3 months (median [IQR], 3.5 ng/L [3.2-4.0], vs 2.6 [1.7-3.4], p = 0.008) and at 12 months (3.6 ng/L [3.5-3.8] vs 2.6 [1.8-3.5], p = 0.049). NfL ratio and index were not associated with outcome. The area under the curve (AUC) for sNfL Z-score was 0.76 (95% CI 0.58-0.93, p < 0.0001) for GBSDS > 2 at 3 months. NfL ratio and index were lower in GBS than HC, MS, and ALS. The AUC for the NfL ratio was 0.66 (95% CI 0.55-0.78, p = 0.0018) and for the NfL index 0.86 (95% CI 0.78-0.93, p < 0.0001).
CONCLUSIONS: Our results confirm sNfL as prognostic biomarker for GBS and the precision was improved using the age-adjusted sNfL Z score. NfL index and Qalb are potential diagnostic biomarkers for GBS.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. The frequency of CIPN ranges from one in three to almost all patients depending on type of chemotherapy and dose. It causes symptoms that can range from sensitivity to touch and numbness to neuropathic pain in hands and feet. CIPN is notoriously difficult to grade objectively and has mostly relied on a clinician- or patient-based rating that is subjective and poorly reproducible. Thus, considerable effort has been aimed at identifying objective biomarkers of CIPN. Recent in vitro, animal, and clinical studies suggest that neurofilament light chain (NFL), a structural neuronal protein, may be an objective biomarker of CIPN. NFL released from cells to cell culture media reflects in vitro neurotoxicity, while NFL in serum reflects neuronal damage caused by chemotherapy in rodent models. Finally, NFL in serum may be a diagnostic biomarker of CIPN, but its prognostic ability to predict CIPN requires prospective evaluation. We discuss current limitations and future perspectives on the use of NFL as a preclinical and clinical biomarker of CIPN.

BACKGROUND: Atrial fibrillation (AF) is an age-related disorder closely linked to autonomic nervous system dysfunction. Neurofilament light chain (NFL) protein is a biomarker for neurodegenerative diseases.
OBJECTIVE: This study aims to evaluate the predictive value of NFL in forecasting AF recurrence following ablation.
METHODS: We included patients initially diagnosed with AF who underwent catheter ablation. Serum NFL levels were measured using an enzyme-linked immunosorbent assay. The primary outcome was AF recurrence during follow-up.
RESULTS: A total of 215 consecutive patients were enrolled, with an average follow-up period of 10.69 months. During this period, 29 patients experienced AF recurrence. Multivariate Cox regression analysis revealed that high NFL levels (≥300 pg/ml) were an independent predictor of recurrence risk (adjusted hazard ratio [HR]: 3.756; 95% confidence interval [CI]: 1.392 to 10.136). The associations between NFL levels and AF recurrence were consistent across subgroups defined by age (>65 years), gender, hypertension, and paroxysmal AF. Restricted cubic spline analysis showed a consistent linear relationship across the entire range of NFL levels. Furthermore, incorporating NFL into the CHA2DS2-VASc score model significantly improved the prediction of recurrent AF risk, as demonstrated by time-dependent area under the curve and decision curve analysis. Notable enhancements were also observed in terms of net reclassification improvement (0.464, 95% CI: 0.226-0.675, P<0.05) and integrated discrimination improvement (0.087, 95% CI: 0.017-0.183, P=0.08).
CONCLUSIONS: NFL may serve as an effective biomarker for risk stratification and therapeutic decision-making in patients with new onset AF who have undergone catheter ablation.

BACKGROUND: Investigating the link between serum neurofilament protein (sNfL) levels and depression remains an area of limited understanding. This study explores the correlation in US adults and employs Mendelian randomization (MR) to ascertain causality.
METHODS: Our cross-sectional study analyzed data from participants aged 20 and above in the National Health and Nutrition Examination Survey (2013-2014). We employed a weighted multiple logistic regression model to examine the relationship between ln (sNfL) and depression. Restricted cubic splines (RCS) were used to visualize non-linear relationships. Stratified analyses examined associations between ln(sNfL) and depression in different subgroups. Subsequently, we conducted a two-sample bidirectional Mendelian randomization (MR) to assess the causal relationship between sNfL and depression. The inverse variance-weighted (IVW) method was utilized as the primary analysis.
RESULTS: Among 1765 participants (mean age 45.19 years; 49.37 % male), 166 had depression with a Patient Health Questionnaire (PHQ-9) score ≥ 10. After adjusting for covariates, a positive correlation remained between sNfL and depression (OR 1.511, 95 % CI: 1.050-2.175). RCS curves indicated a non-linear association, with a turning point at 2.76 pg/ml. Stratified analyses revealed positive correlations in specific subgroups, with interactions involving age, race, family income, recreational activity, and ln(sNfL). MR using IVW found no significant causal relationship between sNfL and depression genetically (OR = 0.956, 95 % CI: 0.878-1.042), with reverse analysis yielding similar results (OR = 0.897, 95 % CI: 0.756-1.065).
CONCLUSIONS: This cross-sectional study highlights a significant correlation between ln(sNfL) and depression. However, MR results indicate no causal relationship between sNfL and depression.

BACKGROUND: Protein biomarkers have been broadly investigated in cerebrospinal fluid and blood for the detection of neurodegenerative diseases, yet a clinically useful diagnostic test to detect early, pre-symptomatic Alzheimer\'s disease (AD) remains elusive. We conducted this study to quantify Aβ40, Aβ42, total Tau (t-Tau), hyperphosphorylated Tau (ptau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) in eye fluids relative to blood.
METHODS: In this cross-sectional study we collected vitreous humor, aqueous humor, tear fluid and plasma in patients undergoing surgery for eye disease. All six biomarkers were quantitatively measured by digital immunoassay. Spearman and Bland-Altman correlation analyses were performed to assess the agreement of levels between ocular fluids and plasma.
RESULTS: Seventy-nine adults underwent pars-plana vitrectomy in at least one eye. Of the 79, there were 77 vitreous, 67 blood, 56 tear fluid, and 51 aqueous samples. All six biomarkers were quantified in each bio-sample, except GFAP and NfL in tear fluid due to low sample volume. All six biomarkers were elevated in vitreous humor compared to plasma samples. T-Tau, ptau181, GFAP and NfL were higher in aqueous than in plasma, and t-Tau and ptau181 concentrations were higher in tear fluid than in plasma. Significant correlations were found between Aβ40 in plasma and tears (r = 0.5; p = 0.019), t-Tau in plasma and vitreous (r = 0.4; p = 0.004), NfL in plasma and vitreous (r = 0.3; p = 0.006) and plasma and aqueous (r = 0.5; p = 0.004). No significant associations were found for Aβ42, ptau181 and GFAP among ocular fluids relative to plasma. Bland-Altman analysis showed aqueous humor had the closest agreement to plasma across all biomarkers. Biomarker levels in ocular fluids revealed statistically significant associations between vitreous and aqueous for t-Tau (r = 0.5; p = 0.001), GFAP (r = 0.6; p < 0.001) and NfL (r = 0.7; p < 0.001).
CONCLUSIONS: AD biomarkers are detectable in greater quantities in eye fluids than in plasma and show correlations with levels in plasma. Future studies are needed to assess the utility of ocular fluid biomarkers as diagnostic and prognostic markers for AD, especially in those at risk with eye disease.

OBJECTIVE: To show that magnetic resonance morphometry and laboratory biomarkers are promising methods for early detection of progressive forms of multiple sclerosis (MS).
METHODS: Eighty-one patients with MS were examined, magnetic resonance morphometry was performed in all of them, 60 patients were analyzed for neurofilament light chains (sNFL), phosphorylated neurofilament heavy chains (spNFH) and glial fibrillary protein (sGFAP) in serum by enzyme-linked immunosorbent assay.
RESULTS: Brain volumes were negatively correlated with disease duration, EDSS score, 25-foot walk test score and 9-ring test and positively correlated with the Symbol-Numeric Test and the Montreal Cognitive Assessment. Patients with progressive types of MS (PMS) had smaller volumes of brain gray matter, cerebellar white matter, occipital lobes, caudate nucleus, hippocampus, pallidum, thalamus, and contiguous nucleus. A CSF volume greater than 15.06% could suggest progression (CI 54.79-91%) with a sensitivity of 77.78% and specificity of 70.18%. When patients were on DMT, they had larger thalamic volumes (median 1.09% [1.6; 1.16] vs 1.04% [0.95; 1.14]; p=0.02) and smaller CSF volumes (13.86±2.87% vs. 15.55±3.49%; p=0.03). The levels of sNFL and spNFH were not increased in PMS and during exacerbations, and the low obtained values of sNFL suggest poor sensitivity of the method. There were trends (p=0.374) towards higher sGFAP in patients with PRS (median 3.2 ng/mL [1.85; 4.6] compared to remitting MS (2.05 ng/mL [1.29; 4.52]).
CONCLUSIONS: The results demonstrate the differences in brain volumes in patients with different types of MS and emphasize the importance of long-term follow-up to better assess disease progression.
UNASSIGNED: Показать, что МРТ-морфометрия (МРТМ) и лабораторные биомаркеры являются перспективными методами раннего выявления прогрессирующих форм рассеянного склероза (ПРС).
UNASSIGNED: Обследован 81 пациент с РС, всем выполнена МРТМ, 60-ти пациентам выполнен анализ легких цепей нейрофиламентов (sNFL), фосфорилированных тяжелых цепей нейрофиламентов (spNFH) и кислого глиального фибриллярного белка (sGFAP) в сыворотке крови методом иммуноферментного анализа.
UNASSIGNED: Выявлены отрицательные корреляционные связи объемов ряда структур головного мозга и продолжительности заболевания, баллов по шкале EDSS, 25-футового теста ходьбы и 9-колышкового теста; положительные — с тестом символьно-цифрового кодирования и Монреальской шкалой оценки когнитивных функций. У пациентов с ПРС наблюдались меньшие объемы серого вещества головного мозга, белого вещества мозжечка, затылочных долей, хвостатого ядра, гиппокампа, бледного шара, таламуса и прилежащего ядра. При объеме цереброспинальной жидкости (ЦСЖ) более 15,06% с чувствительностью 77,78% и специфичностью 70,18% можно предполагать прогрессирование РС (ДИ 54,79—91%). В случае приема препаратов, изменяющих течение РС, у пациентов наблюдались бóльшие объемы таламуса (Me 1,09% [1,06; 1,16] против 1,04% [0,95; 1,14]; p=0,02) и меньшие объемы ЦСЖ (13,86±2,87% против 15,55±3,49%; p=0,03). Уровень sNFL и spNFH не повышался при ПРС и в период обострений, а полученные низкие значения sNFL говорят о слабой чувствительности метода. Имелись тенденции (p=0,374) к повышению sGFAP у пациентов с ПРС (Me 3,2 нг/мл [1,85; 4,6]) по сравнению с ремиттирующим РС нг/мл (2,05 [1,29; 4,52]).
UNASSIGNED: Полученные результаты указывают на различия в объемах поражения головного мозга у пациентов с различными типами РС и подчеркивают важность длительного наблюдения для более точной оценки прогрессирования заболевания.

BACKGROUND: The study seeks to assess serum neurofilament light chain (NfL) levels in paediatric narcolepsy-diagnosed patients. Moreover, it aims to explore the correlation between NfL levels and the severity of narcolepsy symptoms, sleep quality, and manifestations of anxiety and depression.
METHODS: This retrospective analysis included 98 paediatric narcolepsy cases and 100 controls matched for age and gender. The study focused on comparing serum NfL levels across these groups. Severity of EDS in patients was measured with the Epworth Sleepiness Scale (ESS). Moreover, the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale-24 (HAMD-24), and Hamilton Anxiety Scale-14 (HAMA-14) were used to assess narcolepsy symptoms, sleep quality, and psychological conditions.
RESULTS: Patients with paediatric narcolepsy had significantly higher serum NfL levels than controls (P < 0.05). Additionally, a positive correlation was found between serum NfL levels and ESS scores (P < 0.001). An independent link between serum NfL and paediatric narcolepsy was established via multiple logistic regression (OR = 0.943, 95 % CI = 0.921-0.993, P = 0.004). Moreover, serum NfL\'s diagnostic precision for paediatric narcolepsy was evident from the ROC curve area of 0.938 (95 % CI: 0.86-0.99, P < 0.001).
CONCLUSIONS: The study implies a positive correlation between increased serum NfL levels and the severity of paediatric narcolepsy. Nevertheless, the causative link between serum NfL levels and paediatric narcolepsy remains uncertain, highlighting the need for larger sample sizes and well-structured cohort studies to offer more definitive.