Reliable and disease-specific blood biomarkers are critically needed for Alzheimer’s disease (AD), particularly in early stages when interventions are most effective. Although phosphorylated tau and neurofilament light chain (NfL) are widely used, their diagnostic specificity has been reported to decrease in elderly populations with multimorbidities. Syndecan-3 (SDC3), a heparan sulfate proteoglycan implicated in amyloid and tau aggregation, has recently emerged as a mechanistically relevant biomarker candidate. In this clinically realistic cohort study, we examined 46 participants, including 23 clinically diagnosed AD patients and 23 age-matched non-AD individuals with psychiatric and/or metabolic comorbidities. SDC3 expression was quantified in peripheral blood mononuclear cells (PBMCs), while soluble SDC3 and NfL were measured in plasma. Both PBMC-expressed and plasma SDC3 levels were elevated in AD compared with non-AD participants and showed a strong intercorrelation, whereas plasma NfL was likewise increased in AD. Individually, PBMC-SDC3, plasma SDC3, and NfL demonstrated moderate discriminatory performance. However, multivariable models integrating SDC3 (PBMC or plasma), NfL, and age achieved substantially improved discrimination (AUC > 0.8). SDC3 did not correlate with NfL, consistent with a biological signal distinct from neuroaxonal injury and reflective of peripheral immune–metabolic remodeling. Together, these findings identify SDC3 as a blood-based biomarker associated with systemic immune remodeling that complements established neuronal markers in a clinically realistic AD versus non-AD comparison. While exploratory, this study supports further investigation of SDC3 within integrated, multi-domain biomarker strategies in larger and independent cohorts.

Cognitive impairment in SCA3: A multi-center cohort study with demographic, imaging, and biomarker correlates.

Background Cognitive impairment (CI) is a prevalent and early problem in multiple sclerosis (MS). Its detection and monitoring might help prevent cognitive decline and potentially inform treatment decisions. Objective The aim of this study was to analyze the possible associations of cognitive decline and neurofilament levels, disability measures, and disease-modifying treatments (DMTs) in patients with MS (PwMS). Methods 64 PwMS and 14 healthy controls participated in this prospective study. Neurofilament light chain (NfL) levels were measured in the cerebrospinal fluid (CSF) samples of PwMS and serum samples of both groups. Serum samples, cognitive testing using Brief International Cognitive Assessment for MS (BICAMS) battery and disability assessment using EDSS, Nine-Hole Peg Test (9HPT) and Timed 25-Foot Walk Test (T25FWT) were evaluated at the time of diagnosis and at follow-up at 12 months. Longitudinal change in BICAMS subtest scores was calculated and its associations with NfL concentration, disability measures and demographic/clinical data were analyzed. Results All PwMS were diagnosed with relapsing MS and 78.1% were started on platform DMTs, while the rest were prescribed higher-efficacy DMTs. PwMS had significantly higher sNfL concentration at baseline (11.95 vs. 5.40 pg./mL, p = 0.001) but follow-up sNfL levels were similar to those of control group (7.40 vs. 5.50 pg./mL, p = 0.768). At baseline, all BICAMS subtest scores were lower in PwMS, but the difference in the Symbol Digit Modalities Test (SDMT) was not statistically significant. However, it was the only subtest to significantly decrease at follow-up (−1.87, p = 0.024). Correlation analysis showed that SDMT1 and 2 were associated with serum NfL2 measurement. Logistic regression analysis demonstrated that serum NfL at baseline and follow-up were significant predictors for SDMT decline. Platform DMTs, when compared to higher-efficacy DMTs, also significantly increased the odds of SDMT decline. Conclusion Our findings highlight the potential of serum NfL as a marker of early IPS decline. Treatment with higher-efficacy DMTs early after diagnosis may be protective against early cognitive decline in MS.

This review summarizes current evidence on the efficacy and safety of tofersen (Qalsody) in treating amyotrophic lateral sclerosis (ALS). PubMed, MEDLINE, Google Scholar, and ClinicalTrials.gov were searched using the keywords: Qalsody, BIIB067, antisense oligonucleotides, SOD1, and amyotrophic lateral sclerosis. Articles published from inception to November 2025 were included. English-language studies assessing the pharmacokinetics, pharmacology, efficacy, and safety of tofersen were included. Prescribing information and real-world evidence were also reviewed. Tofersen is an intrathecally administered antisense oligonucleotide targeting superoxide dismutase 1 (SOD1) mRNA. Early trials demonstrate dose-dependent reductions in cerebrospinal fluid (CSF) SOD1 protein levels of -33% and slower ALS Functional Rating Scale (ALSFRS-R) decline compared to placebo (-1.19 vs -5.63 points). In Phase 3 trials, tofersen reduced CSF SOD1 by 29% and plasma neurofilament light chain (NfL) by 60%, while biomarkers increased in the placebo group. There was no significant difference in ALSFRS-R decline between tofersen and placebo (-6.98 vs -8.14; P = 0.97). Real-world data show favorable patient-related outcomes and improvement in ALSFRS-R. Adverse effects are primarily lumbar puncture related with serious neurologic events documented in 7% of tofersen recipients.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:As the first Food and Drug Administration (FDA)-approved gene-directed therapy for SOD1 ALS, tofersen directly targets the underlying genetic cause. Barriers include the need for genetic confirmation and intrathecal administration. Tofersen provides a promising targeted treatment option for pathogenic SOD1 ALS. Ongoing studies will clarify its long-term clinical impact.

Neurodevelopmental disorders (NDDs), including autism spectrum disorder, attention deficit/hyperactivity disorder, intellectual disability, and Down syndrome, are increasingly examined through the lens of aging. Emerging evidence indicates that individuals with NDDs may exhibit accelerated or atypical brain aging, characterized by cognitive decline and increased vulnerability to neurodegenerative conditions such as Alzheimer's and Parkinson's disease. This narrative review synthesizes current findings on biological mechanisms implicated in altered aging trajectories, with emphasis on oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and cellular senescence. These processes, detectable from early development, mirror pathways involved in neurodegeneration, suggesting shared molecular cascades that increase susceptibility to early aging. Biomarker studies report telomere shortening, elevated plasma glial fibrillary acidic protein and neurofilament light chain levels, and deviations in neuroimaging-derived brain age, supporting the hypothesis of altered biological aging in NDDs. However, the limited number of longitudinal lifespan studies, along with marked heterogeneity in etiology, clinical profiles, and comorbidities, constrains causal inference. Psychosocial and environmental factors, including chronic stress, social exclusion, medical comorbidities, and lifestyle influences, further shape aging outcomes. Integrating biological, behavioral, and environmental markers is essential to advance monitoring and inform early interventions aimed at promoting healthier cognitive and functional aging in neurodivergent populations.

Inhibition of cAbl tyrosine kinase reduces α-synuclein aggregation, protects dopaminergic neurons, and improves motor function in animal models of Parkinson's Disease (PD). PROSEEK was a Phase 2, randomized, double-blind, placebo-controlled study of the effects on disease progression of Vodobatinib, a brain-penetrant c-Abl inhibitor, in 513 participants with early PD not on symptomatic treatment other than a stable dose of a MAO-B inhibitor. Recently diagnosed subjects with confirmatory Dopamine Transporter Single Photon Emission Computed Tomography (DaT-SPECT) scans were randomized to daily Vodobatinib 384 mg, 192 mg, or placebo. The primary endpoint in Part 1 was the change from baseline to Week 40 in the Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III total score; Part 2 was an optional 36-week extension. There was a high, dose-related rate of early withdrawal. The mean score of completers in the placebo group was slightly lower than at baseline of the entire cohort. Comparisons with either dose group favored the placebo. Serum neurofilament light chains increased significantly in both Vodobatinib groups, supporting inefficacy in PD.

ABSTRACTIntroductionManagement of multiple sclerosis (MS) revolves around timely initiation of effective disease‐modifying therapy. Here we investigate the additive predictive value of age‐adjusted normalised neurofilament light chain (NfL) concentrations when combined with a clinicodemographic model of treatment response.MethodsData were obtained from three sources: the University Hospital Basel, the SET cohort in Prague, and EIMS and IMSE cohorts from Sweden. NfL samples were collected within 90 days of baseline, age‐adjusted and normalised using a reference population. Principal component analysis reduced the dimensionality of clinicodemographic predictors. Cox proportional hazards models estimated cumulative hazards of relapse, 6‐month confirmed disability worsening and 9‐month confirmed disability improvement, with and without NfL. Uno's concordance index compared prediction accuracy across pooled and treatment‐specific models.ResultsThe study included 1716 individuals across three therapies: interferon β (n = 554), fingolimod (n = 307) and natalizumab (n = 369). Clinicodemographic characteristics were associated with relapse and disability outcomes. While NfL showed no association in the pooled cohort, in the natalizumab group, higher NfL predicted lower probability of disability improvement (HR = 0.819, 95% CI: 0.814–0.823). Pooled models predicted outcomes with moderate accuracy (relapse: 63.4%, disability worsening: 56.4%, improvement: 67.7%), with minimal contribution from NfL. In treatment‐specific models, NfL‐inclusive accuracy ranged from 51.3%–62.2% (relapse), 54.3%–60.3% (worsening) and 65%–67.9% (improvement), closely matching models without NfL.ConclusionIn well‐characterised MS patients treated with interferon β, fingolimod or natalizumab, clinicodemographic information provides modest prognostic value; however, NfL adds minimal incremental utility.

Fibromyalgia (FM) is a chronic pain syndrome in which central sensitization has been suggested. Several patients also present with small fibre pathology. Neurofilament light chain (NfL) is a biomarker of axonal injury, but its role in FM remains unclear. We evaluated serum NfL in FM patients and tested possible correlations between NfL levels, clinical features, dysfunction at the central level assessed with a cognitive battery, and small fibre pathology assessed with skin biopsy. We conducted an observational case-control study including 70 FM patients and 55 healthy controls. Serum NfL was measured using the LUMIPULSE G600II platform. Clinical assessment included pain (WPI), disability (FIQ), sleep (MOS Sleep Scale), and neuropsychological testing (MoCA and an executive function battery). Forty patients underwent skin biopsy with intraepidermal nerve fibre density (IENFD) quantification. Group comparisons were performed with non-parametric tests and correlations using Spearman coefficients. FM patients showed higher NfL levels compared to controls, independent of age. In both groups, NfL correlated positively with age (ρ = 0.25, p = 0.005). Among FM patients, NfL values did not differ between those with normal skin biopsy and those with proximal or combined proximal-distal denervation, and NfL did not correlate with IENFD. NfL was unrelated to disease duration, pain scores, sleep duration, or cognitive performance. The only clinical correlation observed was an association with disability (FIQ; ρ = 0.29, p = 0.02). Serum NfL is elevated in FM but not linked to small fibre pathology or cognitive impairment. Instead, it may reflect neuronal changes related to disease burden. These findings support the concept of FM as a neurogenic disorder and suggest serum NfL as a potential biomarker of neuronal stress in chronic pain, although it is not specific for peripheral nerve damage or cognitive dysfunction.

The AOPP-cNOS relay: A Redox-Metabolic pathway in the lung-brain axis of pulmonary hypertension and neurovascular injury.

INTRODUCTIONLittle is known about how Alzheimer's disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers.METHODSThe study involved 251 Wake Forest Multi‐Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, magnetic resonance imaging, amyloid positron emission tomography (PET), and adjudicated cognitive status. Multivariable models examined cross‐sectional relationships between plasma and neuroimaging biomarkers, considering comorbidities.RESULTSLower amyloid beta (Aβ) 42/Aβ40 and higher glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau at threonine 217 (p‐tau217) were associated with greater neurodegeneration. Lower plasma Aβ42/Aβ40 and higher p‐tau217 and p‐tau231 were associated with greater Aβ PET deposition. NfL was positively associated with white matter hyperintensities (WMH) and white matter (WM) free water. P‐tau measures were positively associated with WM free water. Lower Aβ42/Aβ40 was associated with the presence of microbleeds. GFAP was positively associated with WMH.DISCUSSIONWe observed expected associations of plasma biomarkers with cognitive status and imaging biomarkers. GFAP, NfL, p‐tau181, p‐tau217, and p‐tau231 are associated with cSVD in addition to AD‐related pathology.

Xingshen Jieyu Decoction ameliorates post-stroke depression by modulating proBDNF/BDNF signaling via PI3K/Akt pathway.

Super-resolution localization microscopy visualizes ischemia-related cytoskeletal and vascular alterations at the nanoscale level in a mouse model of stroke.

Worsened axonal injury and gliosis following diffuse brain injury in male and female mice with neurofilament light gene deletion.

Vascular damage, including cerebral amyloid angiopathy (CAA) and non-amyloid cerebral small vessel disease (CSVD), has been linked to glymphatic dysfunction, which may contribute to Alzheimer's disease (AD) pathology and cognitive decline. We investigated the associations among vascular damage, glymphatic function measured by the DTI-ALPS (Diffusion Tensor Imaging-Analysis Along the Perivascular Space) index, AD plasma biomarkers, and cognitive decline. This study includes 1,249 participants recruited from Samsung Medical Center. We performed linear regression analysis to identify factors associated with the DTI-ALPS index. Further, linear regression analysis with vascular imaging markers, including CAA and CSVD summary scores, as predictors and DTI-ALPS index as an outcome was performed to investigate the effect of vascular pathology on glymphatic function. We conducted mediation analyses to investigate whether the DTI-ALPS index mediates the effect of vascular imaging markers on plasma biomarkers (phosphorylated tau 217 [p-tau 217], glial fibrillary acidic protein [GFAP], and neurofilament light chain [NFL]). Additionally, mediation analyses with the DTI-ALPS index as a predictor, each plasma biomarker as a mediator, and annual MMSE or CDR-SOB change as an outcome to investigate whether plasma biomarkers mediate the effect of the DTI-ALPS index on longitudinal cognitive decline. First, the DTI-ALPS index was negatively associated with both CAA (β [95% CI] = -0.163 [-0.214, -0.112], p < 0.0001) and CSVD (β [95% CI] = -0.195 [-0.247, -0.143], p < 0.0001) summary scores after controlling for age, sex, BMI status, and APOE genotype. Second, the DTI-ALPS index fully mediated the relationship between these vascular markers and p-tau 217 (CSVD summary score, indirect effect β [95% CI] = 0.016 [0.010, 0.023], p < 0.001; CAA summary score, indirect effect β [95% CI] = 0.013 [0.008, 0.020], p < 0.001) and GFAP (CSVD summary score, indirect effect β [95% CI] = 0.015 [0.008, 0.022], p < 0.001; CAA summary score, indirect effect β [95% CI] = 0.012 [0.007, 0.019], p < 0.001), while partially mediating the relationship for NFL, regardless of Aβ uptake on PET. Finally, the DTI-ALPS index was significantly associated with cognitive decline and this association was partially mediated by plasma biomarkers. These findings highlight glymphatic dysfunction as a key mechanism linking vascular pathology with tau, inflammation and neurodegeneration, independent of Aβ uptakes.

Aim This study aimed to investigate the neuroprotective mechanisms of mechanical thrombectomy (MT) by evaluating its effects on the neurovascular unit (NVU) and correlating these effects with dynamic changes in serum biomarkers in patients with acute ischemic stroke (AIS). Methods A prospective cohort of 128 AIS patients with anterior circulation large vessel occlusion was enrolled. Participants were divided into MT ( n = 68) and intravenous thrombolysis (IVT) ( n = 60) groups. Serum levels of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured at baseline (T0), 24 h (T1), and 72 h (T2) post-treatment. Clinical outcomes included recanalization rate (mTICI grade), NIHSS improvement, and 90-day modified Rankin Scale (mRS) score. Results The MT group showed significantly higher recanalization rates (94.1% vs. 36.7%, p &amp;lt; 0.001) and greater neurological improvement (median NIHSS improvement: 8 vs. 4, p &amp;lt; 0.001) compared to the IVT group. Serum NfL, GFAP, IL-1β, and TNF-α levels were markedly lower in the MT group at T1 and T2 (all p &amp;lt; 0.01). Strong correlations were identified between T2 NfL/GFAP levels and clinical outcomes (NIHSS improvement: r = −0.728/−0.663; 90-day mRS: r = 0.705/0.641; all p &amp;lt; 0.001). Conclusion Successful recanalization with MT is associated with mitigated axonal injury, astrocyte activation, and neuroinflammation, findings consistent with better preservation of NVU integrity. Serum NfL and GFAP represent promising biomarkers for predicting stroke prognosis and tailoring therapeutic strategies.

Identifying objective biomarkers for progressive supranuclear palsy (PSP) is crucial to improving diagnosis and establishing clinical trial and treatment endpoints. This study evaluated fluid biomarkers in PSP versus controls and their associations with regional 18F-PI-2620 tau-PET, clinical, and cognitive outcomes. Twenty-four PSP patients and 11 age- and sex-matched control subjects underwent Cerebrospinal fluid (CSF) and plasma assays of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total tau (t-tau) using SIMOA. Ratios (NfL/t-tau, GFAP/t-tau, GFAP/NfL) were calculated. Tau burden was quantified using PI-2620 distribution volume ratio (DVR). Group comparisons and associations with tau-PET, MRI, and cognition were tested using Wilcoxon tests, ROC analyses, and age- and sex-adjusted linear models. PSP patients showed elevated NfL, GFAP levels, and higher NfL/t-tau and GFAP/t-tau ratios in CSF and plasma. CSF NfL/t-tau best discriminated PSP from control subjects (AUC = 0.99, 95% CI [0.97-1.00]; optimal cut-off: > 10), followed by CSF GFAP/t-tau (AUC = 0.89, 95% CI [0.76-1.00]; > 104) and plasma NfL/t-tau (AUC = 0.80, 95% CI [0.63-0.96]; 5.1). Plasma NfL/t-tau correlated with tau-PET DVR in the putamen (β = 0.63; 95% CI [0.15-1.11]; p < 0.01) and pallidum (β = 0.54, 95% CI [0.07-1.02]; p < 0.01) and predicted disease severity (β = 0.61, 95% CI [0.19, 1.04]; p = 0.007) and processing speed (β = 0.66, 95% CI [0.22, 1.10]; p = 0.006), explaining 35% and 33% of variance, respectively. Frontal MRI volume modestly improved prediction of processing speed (ΔR2adj = 0.23, p = 0.01), whereas tau-PET did not. Plasma NfL/t-tau correlates with regional tau, disease severity, and cognition. Fluid biomarkers, complemented by PET and MRI, may support multimodal PSP diagnosis, monitoring, and trial stratification. Australian New Zealand Clinical Trials Registry: ACTRN12620001254987.

Alzheimer's disease is a common neurodegenerative disease characterized by progressive memory loss, cognitive decline, and behavioral changes. Blood-based biomarkers have recently gained significant attention due to their accessibility and cost-effectiveness. This review highlights the latest progress in multiple key areas of bloodbased biomarkers for Alzheimer's disease. For early diagnosis, blood-based biomarkers such as amyloid-β and phosphorylated tau can identify Alzheimer's disease even before clinical symptoms emerge. Dynamic changes in blood-based biomarkers, including p-tau217 and neurofilament light chain, reflect disease progression and correlate with cognitive decline, enabling continuous monitoring of Alzheimer's disease progression. Additionally, bloodbased biomarkers such as p-tau181 and glial fibrillary acidic protein aid in differential diagnosis by distinguishing Alzheimer's disease from other dementias such as frontotemporal dementia. Blood-based biomarkers related to nerve repair have opened up new avenues for tracking nerve regeneration and therapeutic response, especially brain-derived neurotrophic factor. Furthermore, advanced detection technologies such as single-molecule array and immunoprecipitation-mass spectrometry have significantly improved the sensitivity and specificity of bloodbased biomarkers, facilitating their clinical translation. In summary, blood-based biomarkers hold strong potential to improve early diagnosis, monitor progression, differential diagnosis, and evaluate therapies in Alzheimer's disease. This review provides a comprehensive and updated evaluation of the translational potential of bloodbased biomarkers, emphasizing their practical utility in clinical settings and offering insights into future directions for large-scale application. This review emphasizes the need to prioritize the allocation of scientific resources, expedite the transition of blood-based biomarkers to clinical implementation, and ultimately achieve precise treatment of Alzheimer's disease using these biomarkers.

Physical frailty is associated with adverse health outcomes in older adults, including cognitive decline; however, the underlying biological and pathophysiological mechanisms linking frailty to neuropathological biomarkers remain underexplored, particularly in older adults without dementia. This study examined associations between physical frailty and cognitive performance and biomarkers based on the amyloid, tau, and neurodegeneration (ATN) framework in a sample of community-dwelling older adults without dementia. Using baseline data from a randomized controlled trial, we conducted a secondary cross-sectional analysis of 137 sedentary adults aged 60-85 years with insomnia symptoms and Montreal Cognitive Assessment scores above 17. Frailty was measured using the Johns Hopkins Frailty Assessment Tool. Cognitive performance was assessed with the CogState computerized battery, and plasma biomarkers-including amyloid beta 42/40 ratio (Aβ42/Aβ40), total tau (t-tau), and neurofilament light chain (NfL)-were quantified using Single Molecule Array (Simoa) technology in a subsample (n = 98). In adjusted models, frail participants demonstrated significantly lower global cognition, processing speed, and attention compared to robust individuals. Prefrail participants did not show significant differences in cognitive performance. For biomarkers, prefrail individuals had significantly lower Aβ42/Aβ40 ratios in unadjusted models, and frail individuals showed significantly higher NfL levels in adjusted models. No significant associations were found for t-tau. These findings suggest that physical frailty is linked to both cognitive impairment and early neurobiological changes in older adults without dementia. Incorporating frailty assessments alongside biomarker evaluation may enhance early detection of Alzheimer's-related changes and guide timely interventions to mitigate cognitive decline.

Neurofilament light chain (NfL) is a promising biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). This meta-regression assesses the relationship between treatment effects on serum/plasma NfL (s/pNfL) and clinical and radiological endpoints in randomized controlled trials (RCTs). A systematic PubMed search identified RCTs in MS (1999-2023) with ⩾24 months' duration and s/pNfL data. Extracted outcomes included treatment effects on s/pNfL, annualized relapse rate (ARR), confirmed disability worsening (CDW), magnetic resonance imaging (MRI) new/enlarging T2 lesions, and percentage brain volume change (PBVC). We evaluated the association of treatment effect on the selected outcomes at the trial level by a meta-regression, weighted by trial size and duration. Fifteen RCTs (n = 6814) were included, nine in relapsing MS (RMS, n = 5221), and six in progressive MS (PMS, n = 1593). Treatment effects on s/pNfL showed a moderate association with treatment effects on MRI new/enlarging T2 lesions (R2 = 0.42, p = 0.01), ARR (R2= 0.33, p = 0.03) and CDW (R2= 0.30, p = 0.04), but not with PBVC. In RMS-only trials, association with ARR (R2= 0.45, p = 0.05) and CDW (R2= 0.50, p = 0.03) was more pronounced. In MS, treatment effects on s/pNfL are moderately associated with therapeutic effects on ARR, MRI new/enlarging T2 lesions, and CDW, whereas no consistent association was observed with PBVC.

Multiple sclerosis (MS) is a neurodegenerative central nervous system disorder causing axonal damage and disability. Relapses develop over hours or days and then subside over weeks. Disease-modifying drugs (DMDs) influence disease activity. Interferon beta-1A (IFN-b-1A) is a widely used first-line treatment for relapsing remitting MS (RRMS) that reduces central nervous system inflammation. Fingolimod affects lymphocyte trafficking. B-cell therapy (rituximab) depletes circulating CD20+ B cells in cerebrospinal fluid, but their specific effects in RRMS remain limited. The aim of the present study was to evaluate the effect of DMDs such as IFN-b-1A, fingolimod and rituximab on neurofilament light chain (NFL) and chitinase 3-like 1 (CHI3L1) serum levels, and some biomarkers of plasmacytoid dendritic cells (pDCs) in RRMS patients. Thirty healthy controls and 44 RRMS patients actively receiving their DMDs, were recruited into this study. Patients were divided into three groups according to DMDs type: Group 1 (n = 17) received IFN-b-1A, Group 2 (n = 20) received fingolimod, and Group 3 (n = 7) received rituximab. Patients of all ages and both sexes were included. Serum NFL (84.1% sensitivity and 60.0% specificity) and CHI3L1 (90.9% sensitivity and 73.0% specificity) levels were higher in patients than in controls (p ≤ 0.001), with higher levels of NFL in the B-cell therapy group compared with IFN-b-1A (p ≤ 0.001) and fingolimod (p = 0.005), and higher levels of CHI3L1 in the B-cell group compared to IFN-b-1A (p = 0.001) and fingolimod (p = 0.015). Plasmacytoid dendritic cells showed no difference in tolerogenic and migratory function between the DMDs groups. Disease-modifying drug type (IFN-b-1A, fingolimod, and B-cell therapy) impacts NFL and CHI3L1 serum levels as drug response biomarkers and relates to clinical data of MS patients, but has no diverse impact on the migratory and tolerogenic function of pDCs. The serum NFL and CHI3L1 need to be validated as drug response biomarkers in RRMS patients, evaluating the DMDs' effect on immunocellular level by studying migratory and tolerogenic functions of pDCs.