A5101692389- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Bioinformatics and Genomic Networks
- Inflammation biomarkers and pathways
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Genomics and Chromatin Dynamics
- Extracellular vesicles in disease
- Photoreceptor and optogenetics research
- Genomics and Rare Diseases
- RNA regulation and disease
- Endoplasmic Reticulum Stress and Disease
- Gene expression and cancer classification
- Genetic Associations and Epidemiology
- Retinal Development and Disorders
- RNA and protein synthesis mechanisms
- Advanced battery technologies research
- Nuclear Receptors and Signaling
- Cancer-related molecular mechanisms research
- Memory and Neural Mechanisms
University College London
2015-2021
Nanjing Medical University
2021
GlaxoSmithKline (United Kingdom)
2018
We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) "TAU" MAPT gene). Microarray were validated by qPCR comparison to studies, including association study (GWAS) hits. Immune gene correlated tightly with plaques whereas synaptic genes negatively neurofibrillary tangles. Network analysis immune modules revealed six hub hippocampus amyloid mice, common cortex....
Abstract Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer’s disease (AD). We investigated role primary cultures from wild type mice by using siRNA to decrease Trem2 expression, and parallel knock-in heterozygous or homozygous for R47H AD risk variant. The prevailing phenotype was decreased expression levels microglia, which resulted density microglia hippocampus. Overall, with...
Detecting and treating Alzheimer’s disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels different soluble amyloid-β peptides hippocampus, preceding deposition, relate to genomic changes. Immunoprecipitation-mass spectrometry was used measure early rise a mouse model...
Growing evidence suggests that human gene annotation remains incomplete; however, it is unclear how this affects different tissues and our understanding of disorders. Here, we detect previously unannotated transcription from Genotype-Tissue Expression RNA sequencing data across 41 tissues. We connect to known genes, confirming incomplete, even among well-studied genes including 63% the Online Mendelian Inheritance in Man-morbid catalog 317 neurodegeneration-associated genes. find greatest...
The laying down of memory requires strong stimulation resulting in specific changes synaptic strength and corresponding size dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing shrinking the synapse to prevent damage from too much Ca 2+ influx. But do all types spines serve both these apparently opposite functions? Using confocal microscopy organotypic slices mice expressing green fluorescent protein hippocampal neurones, individual along...
Abstract Background Late stage Alzheimer’s disease and other dementias are associated with neurofibrillary tangles neurodegeneration. Here we describe a mouse (TauD35) carrying human Tau the P301L mutation that results in hyperphosphorylation tangles. Previously have compared gene expression TauD35 mice to which develop plaques but no A similar comparison of pathological features throughout progression is made here between amyloidβ described Parts I II this study. Methods In vitro CA1 patch...
Abstract Genome-wide association studies have reported that, amongst other microglial genes, variants in TREM2 can profoundly increase the incidence of developing Alzheimer’s disease (AD). We investigated role primary cultures from wild type mice by using siRNA to decrease Trem2 expression, and parallel knock-in heterozygous or homozygous for R47H AD risk variant. The prevailing phenotype was decreased expression levels microglia, which resulted density microglia hippocampus. Overall, with...
Abstract There is growing evidence to suggest that human gene annotation remains incomplete, with a disproportionate impact on the brain transcriptome. We used RNA-sequencing data from GTEx detect novel transcription in an annotation-agnostic manner across 13 regions and 28 tissues. found genes highly expressed are significantly more likely be re-annotated, as associated Mendelian complex neurodegenerative disorders. improved of 63% known OMIM-morbid 65% those neurological phenotype....
Abstract Background Progression of Alzheimer’s disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APP Swe / PSEN1 M146V ) show altered transmission, compatible with increased physiological function amyloidβ, before plaques are detected. Recently, the importance microglia has become apparent in human disease. Similarly, TASTPM a close association plaque load upregulated microglial genes. Methods CA1 Synaptic transmission...