Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.

Objective: To investigate the longitudinal dynamics of serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) levels in people with multiple sclerosis (pwMS) under B-cell depleting therapy (BCDT) and their capacity to prognosticate future progression independent of relapse activity (PIRA) events.

Methods: A total of 362 pwMS (1,480 samples) starting BCDT in the Swiss Multiple Sclerosis (MS) Cohort were included. sGFAP levels in 2,861 control persons (4,943 samples) provided normative data to calculate adjusted Z scores.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

Background And Objectives: Plasma β-amyloid-1-42/1-40 (Aβ42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB.

Methods: This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium.

Caregivers' attitudes toward blood-based biomarker testing for Alzheimer's disease.

Introduction: We aimed to evaluate informal caregivers' attitudes toward undergoing and future implementation of blood-based biomarkers (BBBM) testing for Alzheimer's disease (AD).

Methods: We explored caregivers' perspectives, by combining an online survey ( = 107) with a subsequent focus group ( = 7). We used descriptive statistics and thematic content analysis to identify common themes in answers to open-ended survey questions and focus group data.

Clinical Value of Longitudinal Serum Neurofilament Light Chain in Prodromal Genetic Frontotemporal Dementia.

Background And Objectives: Elevated serum neurofilament light chain (NfL) is used to identify carriers of genetic frontotemporal dementia (FTD) pathogenic variants approaching prodromal conversion. Yet, the magnitude and timeline of NfL increase are still unclear. Here, we investigated the predictive and early diagnostic value of longitudinal serum NfL for the prodromal conversion in genetic FTD.

Neurofilament Light and Its Association With CNS Involvement in Patients With Classic Infantile Pompe Disease.

Background And Objectives: Enzyme replacement therapy (ERT) has substantially improved the outcome of classic infantile Pompe disease, an inheritable muscle disease previously fatal at infancy. However, under treatment, patients develop white matter abnormalities and neurocognitive problems. Therefore, upcoming therapies also target the brain.

Urine as matrix for analysis of neurofilament light chain is not suitable to distinguish frontotemporal dementia from psychiatric diseases.

clinical overlap of frontotemporal dementia and primary psychiatric diseases hampers diagnostic distinction, leading to frequent misdiagnosis and diagnostic delay. Neurofilament light chain has shown great potential in CSF and blood for the distinction of frontotemporal dementia from primary psychiatric diseases. Measurement of neurofilament light chain in urine would be even more patient-friendly.

A multimodal marker for cognitive functioning in multiple sclerosis: the role of NfL, GFAP and conventional MRI in predicting cognitive functioning in a prospective clinical cohort.

Background: Cognitive impairment in people with MS (PwMS) has primarily been investigated using conventional imaging markers or fluid biomarkers of neurodegeneration separately. However, the single use of these markers do only partially explain the large heterogeneity found in PwMS.

Objective: To investigate the use of multimodal (bio)markers: i.

Serum Glial Fibrillary Acidic Protein Compared With Neurofilament Light Chain as a Biomarker for Disease Progression in Multiple Sclerosis.

Importance: There is a lack of validated biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS).

Objective: To determine how serum glial fibrillary acidic protein (sGFAP) and serum neurofilament light chain (sNfL) correlate with features of disease progression vs acute focal inflammation in MS and how they can prognosticate disease progression.

Design, Setting, And Participants: Data were acquired in the longitudinal Swiss MS cohort (SMSC; a consortium of tertiary referral hospitals) from January 1, 2012, to October 20, 2022.

Bioinformatics tools and data resources for assay development of fluid protein biomarkers.

Fluid protein biomarkers are important tools in clinical research and health care to support diagnosis and to monitor patients. Especially within the field of dementia, novel biomarkers could address the current challenges of providing an early diagnosis and of selecting trial participants. While the great potential of fluid biomarkers is recognized, their implementation in routine clinical use has been slow.

A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias.

Background: The differential diagnosis of frontotemporal dementia (FTD) is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack of biofluid-based biomarkers.

Objective: To investigate the diagnostic potential of a combination of novel biomarkers in cerebrospinal fluid (CSF) and blood.

Methods: We included 135 patients from the Center for Memory Disturbances, University of Perugia, with the diagnoses FTD (n = 37), mild cognitive impairment due to Alzheimer's disease (MCI-AD, n = 47), Lewy body dementia (PDD/DLB, n = 22), and cognitively unimpaired patients as controls (OND, n = 29).

A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging.

Background And Objectives: To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.

Methods: Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers.

A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies.

Introduction: Neurofilament light (NfL) can be detected in blood of healthy individuals and at elevated levels in those with different neurological diseases. We investigated if the choice of biological matrix can affect results when using NfL as biomarker in epidemiological studies.

Method: We obtained paired serum and EDTA-plasma samples of 299 individuals aged 37-67 years (BiDirect study) and serum samples of 373 individuals aged 65-83 years (MEMO study).

CSF Neurofilament Light Chain Concentrations Predict Outcome in Bacterial Meningitis.

Background And Objectives: Neurofilament light chain (NfL) is a biomarker for neuroaxonal damage and has been found to be elevated proportionally to the degree of neuronal damage in neurologic diseases. The objective of this study was to determine the prognostic accuracy of NfL concentrations on unfavorable outcome in adults with community-acquired bacterial meningitis.

Methods: We measured NfL concentration CSF samples from a prospective cohort study of adults with community-acquired bacterial meningitis in The Netherlands and determined associations between NfL CSF concentrations, clinical characteristics, and outcome in multivariate analyses.

Neurogranin as biomarker in CSF is non-specific to Alzheimer's disease dementia.

We aimed to evaluate the specificity of neurogranin (Ng) for Alzheimer's disease (AD) in a dementia cohort. Cerebrospinal fluid (CSF) Ng was measured (ELISA) in two independent cohorts: (1) clinical (n = 116; age 72±11 years): AD, non-AD (+high T-tau), and controls; and (2) autopsy-confirmed (n = 97; age 71±11 years): AD and non-AD, and 50 controls (age 60±6 years). In 16 autopsy-confirmed AD and 8 control subjects, Ng was measured in tissue (BA6+BA22).

A Cystatin C Cleavage ELISA Assay as a Quality Control Tool for Determining Sub-Optimal Storage Conditions of Cerebrospinal Fluid Samples in Alzheimer's Disease Research.

Background: An N-terminal octapeptide cleavage of the cystatin C protein was discovered by mass spectrometry when cerebrospinal fluid (CSF) was stored at -20°C for 3 months, which did not occur when CSF was stored at -80°C.

Objective: The aim was to develop an immunoassay as quality assessment tool to detect this -20°C cleavage of cystatin C in CSF and support Alzheimer's disease research.

Methods: A specific monoclonal antibody and a double indirect sandwich ELISA were developed: one assay quantifies the octapeptide uncleaved protein specifically and the other quantifies the total cystatin C present in the biological fluid (both cleaved and uncleaved forms).

Ocrelizumab after natalizumab in JC-virus positive relapsing remitting multiple sclerosis patients.

Ocrelizumab is often used as an alternative therapy in natalizumab-treated MS patients at risk for progressive multifocal leukoencephalopathy (PML). Our objective was to assess efficacy and safety of JC-virus positive patients switching (either directly or indirectly) from natalizumab to ocrelizumab. Forty-two patients were included from an observational cohort (median follow-up 21 months).

A neurologist's perspective on serum neurofilament light in the memory clinic: a prospective implementation study.

Background: Neurofilament light in serum (sNfL) is a biomarker for axonal damage with elevated levels in many neurological disorders, including neurodegenerative dementias. Since within-group variation of sNfL is large and concentrations increase with aging, sNfL's clinical use in memory clinic practice remains to be established. The objective of the current study was to evaluate the clinical use of serum neurofilament light (sNfL), a cross-disease biomarker for axonal damage, in a tertiary memory clinic cohort.

Comparing CSF amyloid-beta biomarker ratios for two automated immunoassays, Elecsys and Lumipulse, with amyloid PET status.

Introduction: We evaluated for two novel automated biomarker assays how cerebrospinal fluid (CSF) amyloid beta (Aβ)-ratios improved the concordance with amyloid positron emission tomography (PET) positivity compared to Aβ alone.

Methods: We selected 288 individuals from the Amsterdam Dementia Cohort across the Alzheimer's disease clinical spectrum when they had both CSF and amyloid PET visual read available, regardless of diagnosis. CSF Aβ, phosphorylated tau (p-tau), and total tau (t-tau) were measured with Elecsys and Lumipulse assays, and Aβ with Lumipulse.

Preanalytical Stability of CSF Total and Oligomeric Alpha-Synuclein.

: The role of cerebrospinal fluid (CSF) alpha-synuclein as a potential biomarker has been challenged mainly due to variable preanalytical measures between laboratories. To evaluate the impact of the preanalytical factors contributing to such variability, the different subforms of alpha-synuclein need to be studied individually. : We investigated the effect of exposing CSF samples to several preanalytical sources of variability: (1) different polypropylene (PP) storage tubes; (2) use of non-ionic detergents; (3) multiple tube transfers; (4) multiple freeze-thaw cycles; and (5) delayed storage.

Four subgroups based on tau levels in Alzheimer's disease observed in two independent cohorts.

Background: As Alzheimer's disease (AD) pathology presents decades before dementia manifests, unbiased biomarker cut-points may more closely reflect presence of pathology than clinically defined cut-points. Currently, unbiased cerebrospinal fluid (CSF) tau cut-points are lacking.

Methods: We investigated CSF t-tau and p-tau cut-points across the clinical spectrum using Gaussian mixture modelling, in two independent cohorts (Amsterdam Dementia Cohort and ADNI).

Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy.

Objective: To explore the potential of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of spinal cord degeneration in adrenoleukodystrophy, as objective treatment-outcome parameters are needed.

Methods: Plasma NfL and GFAP levels were measured in 45 male and 47 female ALD patients and compared to a reference cohort of 73 healthy controls. For male patients, cerebrospinal fluid (CSF) samples (n = 33) and 1-year (n = 39) and 2-year (n = 18) follow-up data were also collected.

Assessing the Pre-Analytical Stability of Small-Molecule Metabolites in Cerebrospinal Fluid Using Direct-Infusion Metabolomics.

Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid to aid a reliable interpretation of metabolomics data.

Guidelines for CSF Processing and Biobanking: Impact on the Identification and Development of Optimal CSF Protein Biomarkers.

The field of neurological diseases strongly needs biomarkers for early diagnosis and optimal stratification of patients in clinical trials or to monitor disease progression. Cerebrospinal fluid (CSF) is one of the main sources for the identification of novel protein biomarkers for neurological diseases. Despite the enormous efforts employed to identify novel CSF biomarkers, the high variability observed across different studies has hampered their validation and implementation in clinical practice.