A5084327170- Multiple Sclerosis Research Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- T-cell and B-cell Immunology
- Prion Diseases and Protein Misfolding
- Peripheral Neuropathies and Disorders
- Immune cells in cancer
- Polyomavirus and related diseases
- Alzheimer's disease research and treatments
- Autoimmune Neurological Disorders and Treatments
- Nuclear Receptors and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Barrier Structure and Function Studies
- Stroke Rehabilitation and Recovery
- Rheumatoid Arthritis Research and Therapies
- Cellular transport and secretion
- Cerebrospinal fluid and hydrocephalus
- Radiomics and Machine Learning in Medical Imaging
- Biochemical Acid Research Studies
- Chemokine receptors and signaling
- Bacterial Infections and Vaccines
- Dementia and Cognitive Impairment Research
- Immunotoxicology and immune responses
- Long-Term Effects of COVID-19
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
University Medical Center Utrecht
2021-2025
Vrije Universiteit Amsterdam
2024
Amsterdam University Medical Centers
2021-2024
Netherlands Institute for Neuroscience
2018-2024
University of Amsterdam
2012-2022
Erasmus MC
2022
Amsterdam Neuroscience
2021-2022
Royal Netherlands Academy of Arts and Sciences
2018
University of Southampton
2013-2014
Amsterdam UMC Location University of Amsterdam
2012
An important component of chronic neurodegenerative diseases is the generation an innate inflammatory response within CNS. Microglial and astroglial cells play a key role in development maintenance this response, showing enhanced proliferation activation. We studied time course regulation microglial proliferation, using mouse model prion disease. Our results show that resident accounts for expansion population during identify pathway regulated by activation CSF1R transcription factors PU.1...
Abstract Most tissues are populated by tissue-resident memory T cells (T RM cells), which adapted to their niche and appear be indispensable for local protection against pathogens. Here we show that human white matter-derived brain CD8 + can subsetted into CD103 − CD69 both with a phenotypic transcription factor profile consistent cells. Specifically, expression in correlates reduced of differentiation markers, increased tissue-homing chemokine receptors, intermediate low the factors T-bet...
Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in course. MS lesion pathology shows considerable heterogeneity localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates course using the autopsy cohort Netherlands Brain Bank (NBB), containing 182 brain donors. Using standardized procedure including systematic dissection from standard locations, 3188 tissue blocks 7562...
Abstract Multiple sclerosis is a chronic inflammatory, demyelinating disease, although it has been suggested that in the progressive late phase, inflammatory lesion activity declines. We recently showed Netherlands Brain Bank multiple sclerosis-autopsy cohort considerable ongoing also at end stage of based on microglia/macrophage activity. have now studied role T cells this autopsy cases. quantified and perivascular T-cell cuffing standardized location medulla oblongata 146 sclerosis, 20...
Abstract Microglia nodules (HLA-DR + cell clusters) are associated with brain pathology. In this post-mortem study, we investigated whether they represent the first stage of multiple sclerosis (MS) lesion formation. We show that microglia more severe MS Compared to in stroke, those enhanced expression genes previously found upregulated lesions. Furthermore, lipid metabolism, presence T and B cells, production immunoglobulins cytokines, activation complement cascade, metabolic stress MS....
Abstract Anti-Leucine-rich glioma inactivated-1 (LGI1) and anti-contactin-associated-protein-2 (CASPR2) autoimmune encephalitis (AIE) are common characterized by pathogenic antibodies targeting neuronal autoantigens. However, the drivers of antibody-secreting cells (ASC) involvement T remain unresolved. We performed single cell RNA-sequencing fresh cerebrospinal fluid (CSF) parallel blood samples 15 patients with LGI1- (n=9) CASPR2-AIE (n=6) compared to control (multiple sclerosis (MS) n=15,...
<h3>Background and Objectives</h3> To investigate whether white matter lesion activity, acute axonal damage, density in MS associate with CSF neurofilament light chain (NfL) levels. <h3>Methods</h3> Of 101 brain donors (n = 92 progressive MS, n 9 relapsing-remitting MS), ventricular was collected, NfL levels were measured. White lesions classified as active, mixed, inactive, or remyelinated, microglia/macrophage morphology active mixed ramified, ameboid, foamy. In addition, damage assessed...
Abstract Multiple sclerosis (MS) is a heterogeneous neurological disorder with regards to clinical presentation and pathophysiology. Here, we investigated the heterogeneity of MS by performing an exploratory factor analysis on quantitative qualitative neuropathology data collected for 226 donors in Netherlands Brain Bank autopsy cohort. Three promising dimensions were identified subsequently validated clinical, neuropathological, genetic data. Dimension 1 ranged from predominance...
The study of neurogenesis during chronic neurodegeneration is crucial in order to understand the intrinsic repair mechanisms brain, and key designing therapeutic strategies. In this study, using an experimental model progressive neurodegeneration, murine prion disease, we define temporal dynamics generation, maturation integration new neurons hippocampal dentate gyrus, dual pulse-chase, multicolour γ-retroviral tracing, transmission electron microscopy patch-clamp. We found increased...
Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional relates meningeal subpial injury interest. Using postmortem FFPE...
<h3>Context</h3>Apathy in community-dwelling elderly individuals has been associated with a history of stroke and other cardiovascular disease.<h3>Objective</h3>To assess the relationship between symptoms apathy risk factors or disease (stroke other) large sample people aged 70 to 78 years without depression dementia.<h3>Design</h3>Cross-sectional data analysis within an ongoing cluster-randomized, open, multicenter trial.<h3>Setting</h3>The Netherlands, general...
Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation broader spectrum neuropathologies underlying particular constellation clinical symptoms. In this study, we describe neuropathological findings in 22 patients with anti-IgLON5 from 9 different European centers. 15 (68%), observed hypothalamic brainstem-predominant tauopathy varying severity which...
Over the last few decades, several common single nucleotide polymorphisms (SNPs) have been identified that correlate with clinical outcome in multiple sclerosis (MS), but pathogenic mechanisms underlying effects of these SNPs are unknown. This is part because difficulty functional translation genotype into disease-relevant mechanisms. Building on our recent work showing association disease course post-mortem MS lesion characteristics, we hypothesized would also specific characteristics...
To determine whether B-cell presence in brainstem and white matter (WM) lesions is associated with poorer pathological clinical characteristics advanced MS autopsy cases.Autopsy tissue of 140 24 control cases biopsy patients were examined for CD20+ B cells CD138+ plasma cells. The these was compared characteristics. In corresponding CSF plasma, immunoglobulin (Ig) G ratio oligoclonal band (OCB) patterns determined. a cohort 73 patients, the OCBs determined during follow-up to status at...
Introduction: Patients with glioblastoma (GBM), one of the most aggressive forms primary brain tumors, exhibit a wide range neurologic signs, ranging from headaches to deficits and cognitive impairment, at first clinical presentation. While such variability is attributed inter-individual differences in increased intracranial pressure, tumor infiltration, vascular compromise, direct association disease stage, size location, edema, necrotic cell death has yet be established. The lack...
Abstract Multiple sclerosis (MS) is characterized by neuroinflammation and demyelination of the central nervous system (CNS), leading to disablility 1, 2 . Genetic variants that confer MS risk implicate genes involved in immune function 3 , while related severity disease are associated with preferentially expressed within CNS 4 Current therapies decrease relapse rates preventing immune-mediated damage myelin, but they ultimately fail slow long-term progression, which apparently depends on...
Abstract Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional relates meningeal subpial injury interest. Using post-mortem...
Abstract Multiple sclerosis (MS) is a heterogeneous disorder with regards to clinical presentation and pathophysiology. Stratification into biologically distinct subgroups could enhance prognostication efficacious allocation disease-modifying therapies. In this study, we identified MS by performing clustering analysis on neuropathology data collected for donors in the Netherlands Brain Bank (NBB) autopsy cohort. The input dataset contained detailed information white matter lesion load,...
Abstract Clusters of ramified HLA-DR + cells, known as microglia nodules, are associated with brain pathology. Here we investigated if nodules in the normal-appearing white matter (NAWM) multiple sclerosis (MS) different from (WM) stroke and whether they may relate to start demyelinating MS lesions. We studied relation between pathological severity an autopsy cohort (n=167), compared frequency, size, gene expression (n=7) (n=7). donors (64%) had a higher lesion load proportion active lesions...