Functional discrimination of CSF from Alzheimer's patients in a brain on chip platform.

Neurodegenerative diseases, including Alzheimer's disease (AD), present significant diagnostic challenges due to overlapping symptoms and the invasive, time-consuming, and costly nature of current diagnostic methods. While AD remains the only neurodegenerative disorder for which biomarkers in cerebrospinal fluid (CSF), such as amyloid beta peptide (Aβ), are available for clinical diagnosis, similar tools are lacking for other neurodegenerative conditions. This diagnostic gap hinders timely and accurate differential diagnoses, limiting patient access to appropriate clinical trials and therapeutic interventions.

Clinical use and reporting of neurofilament quantification in neurological disorders: A global overview.

Introduction: Neurofilament light chain (NfL) quantification aids in diagnosing and predicting neurological disorders, but clinical and laboratory practices vary across centers. Differences in result interpretation and reporting further challenge test commutability. This study aimed to review the global analytical and post-analytical methods used for NfL measurement in routine clinical practice across different contexts.

Impact of the intronic RFC1 expansion size in CANVAS phenotype: an oculomotor study.

The identification of the RFC1 homozygous intronic expansion in cerebellar ataxia neuropathy and vestibular areflexia syndrome (CANVAS) highlighted that genetically determined CANVAS patients exhibit a wide range of clinical presentations and natural course. Previous studies suggested a link between disease severity and the size of the intronic expansion. The aim of our study was to obtain quantitative data related to vestibular and cerebellar impairments using oculomotor recordings to provide further evidence of a link between RFC1 intronic expansion size and the phenotype.

Soluble SorLA in CSF, a novel biomarker to explore disrupted trafficking of SorLA protein in Alzheimer disease.

Background: The SorLA protein, encoded by the Sortilin-related receptor 1 (SORL1) gene, is a major player in Alzheimer's disease (AD) pathophysiology. Functional studies demonstrated that SorLA deficiency results in increased production of Aβ peptide, and thus a higher risk of AD. SorLA can be subject to proteolytic shedding at the cell surface, leading to the release of the soluble ectodomain of the protein (sSorLA) in the extracellular space.

Toward alpha-synuclein seed amplification assay in clinical practice.

Introduction: Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility in routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents to facilitate its clinical implementation.

Demyelinating neuropathy as the initial presentation of familial E200K Creutzfeldt-Jakob disease in two patients.

Objective: To describe peripheral neuropathy associated with familial Creutzfeldt-Jakob disease.

Methods: We report two unrelated patients with genetic Creutzfeldt-Jakob disease with demyelinating peripheral neuropathy as initial presentation, with a comprehensive clinical, electrophysiological and neuropathological description.

Results: Both patients exhibited gait disturbance and paresthesia.

A French multicenter analytical evaluation of the automated Lumipulse G sNfL blood assay (Fujirebio®) and its comparison to four other immunoassays for serum neurofilament light chain assessment in clinical settings.

Objectives: Measurement of serum neurofilament light chain (sNfL) protein is becoming a key biomarker for many neurological diseases. Several immunoassays have been developed to meet these clinical needs, revealing significant differences in terms of variability and results. Here, we propose a French multicenter comparison of 5 sNfL assays.

Functional and Molecular Characterization of New Missense Variants in Patients with Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1).

Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the or variants. These variants modify the preferred substrate of serine palmitoyl transferase, responsible for the first step of sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis.

Identification of rare variants in the FBXO38 gene of patients with chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated neuropathy for which there is no clearly identified risk factor. The present study identified rare variants in the FBXO38 gene in three familial cases of CIDP with response to corticosteroids in three generations with incomplete penetrance, and in an unrelated fourth case with diffuse nerve hypertrophy. FBXO38 may be involved in the regulation of the immunity mediated by CD8 T cells, which have an important role in CIDP pathophysiology, through PD1 degradation.

A previously unreported NARS1 variant causes dominant distal hereditary motor neuropathy in a French family.

Background And Aims: Pathogenic variants in the NARS1 gene, which encodes for the asparaginyl-tRNA synthetase1 (NARS1) enzyme, were associated with complex central and peripheral nervous system phenotypes. Recently, Charcot-Marie-Tooth (CMT) disease has been linked to heterozygous pathogenic variants in NARS1 in nine patients. Here, we report two brothers and their mother from a French family with distal hereditary motor neuropathy (dHMN) carrying a previously unreported NARS1 variant.

Prospective 25-year surveillance of prion diseases in France, 1992 to 2016: a slow waning of epidemics and an increase in observed sporadic forms.

BackgroundPrion diseases are rare, fatal disorders that have repeatedly raised public health concerns since the early 1990s. An active prion disease surveillance network providing national level data was implemented in France in 1992.AimWe aimed to describe the epidemiology of sporadic, genetic and infectious forms of prion diseases in France since surveillance implementation.

[Neurofilaments: a key new biomarker for clinicians. Part 2: Neurofilaments, an asset beyond neurodegenerative diseases].

Neurofilaments (Nf) are proteins selectively expressed in the cytoskeleton of neurons, and their increase is a marker of neuronal damage. The potential utility of neurofilament light chain (NfL) has recently increased considerably, well beyond neurodegenerative diseases, due to analytical advances that allow measurement of their concentrations (even low ones) in cerebrospinal fluid and blood. This article completes the first part, in which we presented the interest of NfL in the context of neurodegenerative diseases.

[Neurofilaments: a key new biomarker for clinicians. Part 1: Importance of neurofilaments in the management of neurodegenerative diseases].

Neurological biomarkers are of great use for clinicians, as they can be used for numerous purposes: guiding clinical diagnosis, estimating prognosis, assessing disease stage and monitoring progression or response to treatment. This field of neurology has evolved considerably in recent years due to analytical improvements in assay methods, now allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in blood. This progress greatly facilitates the repeated quantification of biomarkers, the collection of blood being much less invasive than that of CSF.

Neurofilaments contribution in clinic: state of the art.

Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease.

Modeling Neurodegenerative Diseases Using Compartmentalized Microfluidic Devices.

The human brain is a complex organ composed of many different types of cells interconnected to create an organized system able to efficiently process information. Dysregulation of this delicately balanced system can lead to the development of neurological disorders, such as neurodegenerative diseases (NDD). To investigate the functionality of human brain physiology and pathophysiology, the scientific community has been generated various research models, from genetically modified animals to two- and three-dimensional cell culture for several decades.

Charge detection mass spectrometry on human-amplified fibrils from different synucleinopathies.

Amyloid fibrils are self-assembled mesoscopic protein aggregates, which can accumulate to form deposits or plaques in the brain. amplification of fibrils can be achieved with real-time quaking-induced conversion (RT-QuIC). However, this emerging technique would benefit from a complementary method to assess structural properties of the amplification products.

Post malaria acute motor axonal neuropathy.

We report herein the first case of acute motor axonal neuropathy syndrome after severe Plasmodium falciparum malaria in a traveller, diagnosed through neurophysiological findings and high level of neurofilaments light chain in cerebrospinal fluid analysis, with negative testing for anti-ganglioside antibodies.

Proteinopathies associated to repeat expansion disorders.

The most common neurodegenerative disorders, such as Alzheimer's or Parkinson's diseases, are characterized by synaptic dysfunction, neuronal loss and proteinaceous aggregates in central nervous system. The deposition of misfolded proteins constitutes neuropathological hallmarks of these diseases, grouped in the generic term of proteinopathies. Apart from these, other neurodegenerative diseases are characterized by genetic abnormalities like unstable repetitive simple sequence tracts (microsatellites) dispersed throughout the human genome.

Comparative diagnosis interest of NfL and pNfH in CSF and plasma in a context of FTD-ALS spectrum.

Objective: The 'Frontotemporal dementia-Amyotrophic lateral sclerosis Spectrum' (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS.

Methods: First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls.