A5088378152- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- Multiple Sclerosis Research Studies
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Gut microbiota and health
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- Ginseng Biological Effects and Applications
- Health, Environment, Cognitive Aging
- Gene expression and cancer classification
- Neurological Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Acute Lymphoblastic Leukemia research
- Polyomavirus and related diseases
- Mycobacterium research and diagnosis
Amsterdam Neuroscience
2018-2025
Amsterdam University Medical Centers
2019-2025
Vrije Universiteit Amsterdam
2020-2025
Northwestern University
2022-2025
University Medical Center Utrecht
2022
Biomedical Primate Research Centre
2022
Amsterdam UMC Location Vrije Universiteit Amsterdam
2022
Cerebrospinal fluid (CSF) contains a tightly regulated immune system. However, knowledge is lacking about how CSF immunity altered with aging or neurodegenerative disease. Here, we performed single-cell RNA sequencing on from 45 cognitively normal subjects ranging 54 to 82 years old. We uncovered an upregulation of lipid transport genes in monocytes age. then compared this cohort 14 impaired subjects. In subjects, downregulation occurred concomitantly cytokine signaling CD8 T cells. Clonal...
Advances in spatial omics technologies now allow multiple types of data to be acquired from the same tissue slice. To realize full potential such data, we need spatially informed methods for integration. Here, introduce SpatialGlue, a graph neural network model with dual-attention mechanism that deciphers domains by intra-omics integration location and measurement followed cross-omics We demonstrated SpatialGlue on different using technologies, including epigenome-transcriptome...
Abstract Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, thereby contributing significantly to clinical disability. However, pathological mechanisms meningeal inflammation-induced cortical pathology are still largely elusive. By extensive analysis microglia post-mortem tissue, we identified areas two MS-specific microglial populations, termed MS1 MS2 cortex. The population was characterized by a higher...
Alzheimer's disease (AD) therapies utilizing amyloid-β (Aβ) immunization have shown potential in clinical trials. Yet, the mechanisms driving Aβ clearance immunized AD brain remain unclear. Here, we use spatial transcriptomics to explore effects of both active and passive brain. We compare actively patients with nonimmunized neurologically healthy controls, identifying distinct microglial states associated clearance. Using high-resolution alongside single-cell RNA sequencing, delve deeper...
Alzheimer's disease, progressive supranuclear palsy and frontotemporal dementia are characterized by neuronal expression of aberrant tau protein, hyperphosphorylation (pTAU), aggregation neurofibrillary tangle formation sequentially culminating into cell death, a process termed tauopathy. Our aim was to address at which tauopathy stage neuroinflammation starts study the related microglial phenotype. We used Thy1-hTau.P301S (PS) mice expressing human with P301S mutation specifically in...
Multiple sclerosis (MS) is a chronic demyelinating disease characterised by immune cell infiltration resulting in lesions that preferentially affect periventricular areas of the brain. Despite research efforts to define role various cells MS pathogenesis, focus has been on few populations while full-spectrum analysis, encompassing others such as natural killer (NK) cells, not performed. Here, we used single-cell mass cytometry (CyTOF) profile landscape brain – septum and choroid plexus...
Abstract Background Alzheimer’s disease (AD) is the most frequent cause of dementia. Recent evidence suggests involvement peripheral immune cells in disease, but underlying mechanisms remain unclear. Methods We comprehensively mapped changes AD patients with mild cognitive impairment (MCI) or dementia compared to controls, using cytometry by time-of-flight (CyTOF). Results found an adaptive signature AD, and specifically highlight accumulation PD1 + CD57 CD8 T effector memory re-expressing...
Cladribine tablets are an effective treatment for relapsing remitting multiple sclerosis (RRMS). However, almost half of the treated patients not free disease activity after two years. The aim this study was to describe changes that cladribine effectuate in gut and oral microbiota peripheral immunological profile between responders non-responders. In pilot multicenter, prospective, observational BIA (Brain-Immune-Intestine Axis) study, we included aged 18 55 years with RRMS who were...
Microglia and border-associated macrophages (BAMs) are critical for brain health, their dysfunction is associated to disease. Replacing holds substantial therapeutic promise but remains challenging. Here, we demonstrate that monocytes can efficiently replace all macrophages. Monocytes readily replaced embryonal BAMs upon depletion engrafted as monocyte-derived microglia (Mo-Microglia) more sustained niche availability. Mo-Microglia expanded comparably embryonic counterparts showed similar...
Summary Microglia dynamically adapt their morphology and function during increasing age. However, the mechanisms behind these changes are to date poorly understood. Glucocorticoids ( GC s) long known utilized for immunomodulatory actions endogenous levels described alter with advancing We here tested hypothesis that age‐associated elevations in implicate microglia morphology. Our data indicate a decrease microglial complexity concomitant increase aging. Interestingly, enhancing young mice...
Abstract With the advent of spatial multi-omics, we can mosaic integrate such datasets with partially overlapping modalities to construct higher dimensional views source tissue. SpaMosaic is a multi-omics integration tool that employs contrastive learning and graph neural networks modality-agnostic batch-corrected latent space suited for analyses like domain identification imputing missing omes. Using simulated experimentally acquired datasets, benchmarked against single-cell methods. The...
Aging coincides with major changes in brain immunity that aid a decline neuronal function. Here, we postulate systemic, pro-aging factors contribute to immunological occur within the during aging. To investigate this hypothesis, comprehensively characterized central and peripheral immune landscape of 20-month-old male mice using cytometry by time-of-flight (CyTOF) investigated role age-associated circulating factors. We found CD8+ T cells expressing programmed cell death protein 1 (PD1)...
Immunological factors are the key to pathogenesis of multiple sclerosis (MS). Conjointly, environmental known affect MS disease onset and progression. Several studies have found that intestinal microbiota in patients differs from control subjects. One study a trend toward lower species richness with active versus remission. The plays an important role shaping immune system. Recent suggest presence association between gut inflammatory pathways central nervous However, function this...
<title>Abstract</title> With the advent of spatial multi-omics, we can mosaic integrate diverse datasets with partially overlapping modalities to construct consensus multi-modal atlases source tissue. SpaMosaic is a multi-omics integration tool that employs contrastive learning and graph neural networks modality-agnostic batch-corrected latent space suited for analyses like domain identification imputing missing omes. Using simulated experimentally acquired datasets, benchmarked against...
Abstract Background Recent advances in Alzheimer’s disease (AD) therapeutics involve immunization against amyloid‐β (Aβ). Post‐mortem brain analysis from the first active Aβ immunotherapy trial indicated clearance of some AD patients. Yet, mechanisms regulating following remain unknown. Method Here, we utilized a novel spatial proteogenomics approach to study tissues 13 patients immunized with Aβ. We compared these actively patient brains non‐immunized and non‐neurologic controls....
Abstract Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, contributing to clinical disability. However, pathological mechanisms meningeal inflammation-induced cortical pathology are still largely elusive. Using extensive analysis human post-mortem tissue, we identified two distinct microglial phenotypes, termed MS1 MS2, patients. These phenotypes differed morphology protein expression, but both associated...
Abstract Background Emerging evidence suggests that peripheral immunity plays an important role in the progression of Alzheimer’s disease (AD) (Gate et al., 2020). However, more understanding on how immune cells respond to AD pathology is needed before utilizing system further for early diagnosis and therapeutic treatment. Here, we aimed map stages amyloidosis. In addition, characterize aged study effect age‐related circulating factors response. Method We used 6‐month‐old APPswe/PS1dE9...
Abstract Multiple sclerosis (MS) is a chronic demyelinating disease characterised by immune cell infiltration resulting in lesions that preferentially affect periventricular areas of the brain. Despite research efforts to define role various cells MS pathogenesis, focus has been on few populations while full-spectrum analysis, encompassing others such as natural killer (NK) cells, not performed. Here, we used single-cell mass cytometry (CyTOF) profile landscape brain – septum and choroid...