A5025553349- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- Bioinformatics and Genomic Networks
- Blood properties and coagulation
- Single-cell and spatial transcriptomics
- Cholinesterase and Neurodegenerative Diseases
- Acute Ischemic Stroke Management
- Prion Diseases and Protein Misfolding
- Circular RNAs in diseases
- Neurological Disorders and Treatments
- RNA Research and Splicing
- Computational Drug Discovery Methods
- Lipid metabolism and disorders
- Cardiac electrophysiology and arrhythmias
- Immune cells in cancer
- Cardiac Imaging and Diagnostics
- Endoplasmic Reticulum Stress and Disease
- Advanced MRI Techniques and Applications
- Epigenetics and DNA Methylation
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Protease and Inhibitor Mechanisms
- Cerebrovascular and Carotid Artery Diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
UK Dementia Research Institute
2019-2025
University College London
2013-2025
National Hospital for Neurology and Neurosurgery
2013-2023
Institute of Child Health
2023
Research Network (United States)
2023
VIB-KU Leuven Center for Brain & Disease Research
2013-2020
Vlaams Instituut voor Biotechnologie
2016-2020
University of London
2020
University of Milan
2020
KU Leuven
2013-2019
Gene expression profiles of more than 10,000 individual microglial cells isolated from cortex and hippocampus male female App
Research Article9 September 2013Open Access Alteration of the microRNA network during progression Alzheimer's disease Pierre Lau VIB Center for Biology Disease, Leuven, Belgium Human Genetics, Leuven Institute Neurodegenerative Disorders (LIND) University Hospitals and O&N4, Herestraat Search more papers by this author Koen Bossers Neurogeneration Group, Netherlands Neuroscience, an Royal Academy Arts Sciences, Amsterdam, The Rekin's Janky Laboratory Computational Biology, Genetics Evgenia...
Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, it allows transcriptomic profiling of frozen tissue. However, unclear whether snRNA-seq able detect cellular state in human Indeed, analyses brain samples have failed a consistent microglial activation signature Alzheimer's disease. Our comparison microglia from single cells and nuclei four subjects reveals that, although most genes show similar relative abundances nuclei, small population (∼1%)...
Alzheimer's disease (AD) is characterized by synaptic loss, which can result from dysfunctional microglial phagocytosis and complement activation. However, what signals drive aberrant microglia-mediated engulfment of synapses in AD unclear. Here we report that secreted phosphoprotein 1 (SPP1/osteopontin) upregulated predominantly perivascular macrophages and, to a lesser extent, fibroblasts. Perivascular SPP1 required for microglia engulf upregulate phagocytic markers including C1qa, Grn...
Neural stem cells residing in the hippocampal neurogenic niche sustain lifelong neurogenesis adult brain. Adult (AHN) is functionally linked to mnemonic and cognitive plasticity humans rodents. In Alzheimer's disease (AD), process of generating new neurons at impeded, yet mechanisms involved are unknown. Here we identify miR-132, one most consistently downregulated microRNAs AD, as a potent regulator AHN, exerting cell-autonomous proneurogenic effects neural their progeny. Using distinct AD...
<h3>Objective:</h3> We evaluated microRNAs (miRNAs) as potential biomarkers for Alzheimer disease (AD) by analyzing the expression level of miRNAs in CSF patients with AD dementia and nonaffected control subjects. <h3>Methods:</h3> Using quantitative PCR, we profiled 728 subjects clinically ascertained dementia, further compared candidate 37 35 dementia. <h3>Results:</h3> The hsa-miR-27a-3p is reduced due to 2 different cohorts (cohort 1: <i>p</i> = 0.008; cohort 2: 0.015; 2-tailed unpaired...
Abstract Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer’s disease, by its enrichment in transcriptional networks expressed microglia. However, function OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic disease and 1234 control individuals, confirm variant, rs1131454, is associated increased for disease. The same locus has been recently severe coronavirus 2019 (COVID-19) outcomes, linking both diseases....
Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are main source pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating oligodendrocytes an important human brain and play a key role promoting abnormal neuronal hyperactivity AD knock-in mouse model. We show selectively suppressing oligodendrocyte production improves pathology restores function model vivo. Our findings...
Overwhelming evidence indicates that the Aβ (amyloid β-peptide) plays a critical role in pathogenesis of Alzheimer's disease. is derived from APP precursor protein) by action two aspartyl proteases (β- and γ-secretases) are leading candidates for therapeutic intervention. member multigene family includes APLP1 precursor-like protein 1) APLP2. Both APLPs processed manner analogous to APP, with all three proteins subject ectodomain shedding subsequent cleavage γ-secretase. Careful study has...
The cause of sporadic Alzheimer's disease (AD) remains unclear. Given the growing evidence that protein aggregates can spread in a "prion-like" fashion, we reasoned small population brain cells producing such particles due to postzygotic acquired mutation would be sufficient trigger disease. Deep DNA sequencing technology should principle allow detection mosaics.To detect somatic mutations genes causing AD present number cells, developed targeted deep approach scrutinize genomic loci APP,...
IL-22 plays a critical role in defending against mucosal infections, but how production is regulated incompletely understood. Here, we show that mice lacking IL-33 or its receptor ST2 (IL-1RL1) were more resistant to Streptococcus pneumoniae lung infection than wild-type animals and single-nucleotide polymorphisms IL33 IL1RL1 associated with pneumococcal pneumonia humans. The effect of on S. was mediated by negative regulation innate lymphoid cells (ILCs) independent ILC2s as well IL-4 IL-13...
Amyloid β-protein (Aβ) sequence length variants with varying aggregation propensity coexist in vivo, where coaggregation and cross-catalysis phenomena may affect the process. Until recently, naturally occurring amyloid were believed to begin at or after canonical β-secretase cleavage site within precursor. However, N-terminally extended forms of Aβ (NTE-Aβ) recently discovered contribute Alzheimer's disease. Here, we have used thioflavin T fluorescence study kinetics Aβ42 N-terminal...
RNA analysis at the cellular resolution in human brain is challenging. Here, we describe an optimised approach for detecting single transcripts a cell-type specific manner frozen tissue using multiplexed fluorescent RNAscope probes. We developed new robust analytical quantification. Our method shows that low integrity does not significantly affect signal, recapitulates bulk and provides spatial context to transcriptomic of post-mortem single-cell resolution. In summary, our allows usage...
Abstract Ageing underlies functional decline of the brain and is primary risk factor for several neurodegenerative conditions, including Alzheimer’s disease (AD). However, molecular mechanisms that cause during ageing, how these contribute to AD pathogenesis, are not well understood. The objective this study was identify biological processes altered ageing in hippocampus modify Ad lifespan, then putative gene drivers programmes. We integrated common human genetic variation associated with...
Neurodegenerative diseases are characterized by the localized loss of neurons. Why cell death is triggered only in specific neuronal populations and whether it response to toxic insults or initial cellular state that determines their vulnerability unknown. To understand individual responses disease, we profiled transcriptional signatures throughout disease development a Drosophila model C9orf72 (G4C2) repeat expansion (C9), most common genetic cause frontotemporal dementia amyotrophic...