Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation.

Neuroinflammation is often characterized by immune cell infiltrates in the cerebrospinal fluid (CSF). Here, we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious, and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression.

Proteomics Reveals Age as Major Modifier of Inflammatory CSF Signatures in Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) can start as relapsing or progressive. While their clinical features and treatment responses are distinct, it has remained uncertain whether their pathomechanisms differ. A notable age-related effect on MS phenotype and response to immunotherapies is well acknowledged, but the underlying pathophysiologic reasons are yet to be fully elucidated.

A Genetic Risk Variant for Multiple Sclerosis Severity is Associated with Brain Atrophy.

The minor allele of the genetic variant rs10191329 in the DYSF-ZNF638 locus is associated with unfavorable long-term clinical outcomes in multiple sclerosis patients. We investigated if rs10191329 is associated with brain atrophy measured by magnetic resonance imaging in a discovery cohort of 748 and a replication cohort of 360 people with relapsing multiple sclerosis. We observed an association with 28% more brain atrophy per rs10191329*A allele.

The impact of disease-modifying therapies on immunoglobulin blood levels in patients with multiple sclerosis: a retrospective cross-sectional study.

Background: Although disease-modifying therapies (DMTs) in multiple sclerosis (MS) are known to target the immune system, mechanisms of action, efficacy, safety, and tolerability profiles differ. The long-term impact of DMTs on the immune system and its relation to infectious complications is still poorly understood.

Objectives: To analyze the effect of DMTs on serum immunoglobulin (Ig) levels under consideration of patient demographics and therapy duration.

Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients.

Background: Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab.

Drug Treatment of Neuromyelitis Optica Spectrum Disorders: Out with the Old, in with the New?

Introduction: Neuromyelitis optica spectrum disorders (NMOSD) are rare neuroinflammatory demyelinating diseases of the CNS, mainly affecting optic nerves, spinal cord and brainstem regions. The diagnosis depends on clinical symptoms, MRI findings and the detection of autoantibodies against the water channel aquaporin 4 (AQP4-Ab). This autoantibody is particularly important for diagnostic sensitivity and specificity and further sets the course for major therapeutic decisions.

Genetic Variation in WNT9B Increases Relapse Hazard in Multiple Sclerosis.

Objective: Many multiple sclerosis (MS) genetic susceptibility variants have been identified, but understanding disease heterogeneity remains a key challenge. Relapses are a core feature of MS and a common primary outcome of clinical trials, with prevention of relapses benefiting patients immediately and potentially limiting long-term disability accrual. We aim to identify genetic variation associated with relapse hazard in MS by analyzing the largest study population to date.

Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease.

Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated through the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analyzed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks: (i) the percentage area immunostained for vascular collagen IV and laminin was quantified; (ii) the capillary BM thickness as well as endothelial and pericyte pathological changes were analysed using transmission electron microscopy (TEM); and (iii) the presence of vascular Aβ was assessed.

Interplay between age, cerebral small vessel disease, parenchymal amyloid-β, and tau pathology: longitudinal studies in hypertensive stroke-prone rats.

Background: Accumulation of amyloid-β (Aβ) and hyperphosphorylated tau (ptau) accompany cerebral small vessel disease (CSVD) in the aging brain and in Alzheimer's disease. CSVD is characterized by a heterogeneous spectrum of histopathological features possibly initiated by an endothelial dysfunction and blood-brain barrier (BBB) breakdown.

Objective: We test the hypothesis that characteristic features of CSVD are associated with the accumulation of Aβ and ptau in non-transgenic spontaneously hypertensive stroke-prone rats (SHRSP).