Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer’s disease mouse model.

ABSTRACT: Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer’s disease mouse model.

PROVIDER: PRJNA1107236 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR28878921_1.fastq.gz	Fastqsanger.gz
	SRR28878921_2.fastq.gz	Fastqsanger.gz
	SRR28878922_1.fastq.gz	Fastqsanger.gz
	SRR28878922_2.fastq.gz	Fastqsanger.gz
	SRR28878923_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 64

Similar Datasets

Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer’s disease mouse model.

Project description:Background: In Alzheimer’s disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue. Methods: Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113). Results: Treatment resulted in significant reductions in amyloid-beta (Aβ) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice. Conclusions: This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.

2024-05-07 | GSE266470 | GEO

Analysis of Amyloid Plaque Composition in two mouse models of Alzheimer’s disease

Project description:MALDI mass spectrometry imaging (MSI) enables label-free, spatially resolved analysis of a wide range of analytes in tissue sections. Quantitative analysis of MSI datasets is typically performed on single pixels or manually assigned regions of interest (ROI). However, many sparse, small objects such as Alzheimer’s disease (AD) brain deposits of amyloid peptides called plaques are neither single pixels nor ROI. Here, we propose a new approach to facilitate comparative computational evaluation of amyloid plaque-like objects by MSI: a fast PLAQUE PICKER tool that enables statistical evaluation of heterogeneous amyloid peptide composition. Comparing two AD mouse models, APP NL-G-F and APP PS1, we identified distinct heterogeneous plaque populations in the NL-G-F model, but only one class of plaques in the PS1 model. We propose quantitative metrics for the comparison of technical and biological MSI replicates.

2020-10-15 | PXD020824 | Pride

Single nucleus RNA-seq of brain regions showing high-low Abeta plaque pathology in a mouse model of Alzheimer’s disease

Project description:Alzheimer’s Disease (AD) pathology and amyloid-beta plaque deposition progress slowly in the cerebellum compared to other regions, while the entorhinal cortex (EC) is one of the most vulnerable regions. Using a knock-in mouse model (App KI) of preclinical AD, we show that within the cerebellum, the deep cerebellar nuclei (DCN) show particularly low Aβ plaque accumulation. To identify factors that might underlie differences in the progression of AD-associated neuropathology across regions, we profiled gene expression in single nuclei (snRNAseq) across all celltypes in the DCN and EC of wild-type and App KI male mice at age 7 months.

2023-08-31 | GSE214244 | GEO

microRNA-132/212 deficiency enhances Ab production and senile plaque deposition in Alzheimer’s disease triple transgenic mice

Project description:The abnormal regulation of amyloid-b (Ab) metabolism (e.g., production, cleavage, clearance) plays a central role in Alzheimer’s disease (AD). Among endogenous factors believed to participate in AD progression are the small regulatory non-coding microRNAs (miRs). In particular, the miR-132/212 cluster is severely reduced in the AD brain. In previous studies we have shown that miR-132/212 deficiency in mice leads to impaired memory and enhanced Tau pathology as seen in AD patients. Here we demonstrate that the genetic deletion of miR-132/212 promotes Ab deposition and amyloid (senile) plaque formation in triple transgenic AD (3xTg-AD) mice. Using RNA-Seq and bioinformatics, we identified genes of the miR-132/212 network with documented roles in the regulation of Ab metabolism, including Tau, Mapk, and Sirt1.

2016-07-17 | GSE84481 | GEO

Integrative single-plaque analysis reveals signature Aβ and lipid profiles in the Alzheimer’s brain

Project description:Utilizing multimodal mass spectrometry imaging (MSI) combined with machine learning techniques, this study investigates the molecular heterogeneity of amyloid-β (Aβ) plaques and associated lipid profiles in post-mortem brain samples from Alzheimer’s disease (AD) and amyloid-positive cognitively unaffected (AP-CU) individuals. Our analytical approach permitted single-plaque level investigation, revealing distinct populations of amyloid plaques characterized by differential Aβ and lipid compositions. Notably, the integration of MSI data with machine learning based feature extraction enabled the identification of Aβ38 and ganglioside GM1 as significant molecular markers differentiating AD from AP-CU pathology. These findings suggest that the heterogeneity in Aβ metabolism and lipid homeostasis, as revealed through precise analysis, is a key factor in the pathogenesis of AD and implies that total amyloid burden alone is an insufficient marker for the disease. The application of MSI and machine learning based feature extraction in this context exemplifies a progressive analytic strategy to unravel complex biochemical phenomena, offering potential pathways for the refinement of diagnostic tools and deepening the understanding of neurodegenerative diseases from an analytical chemistry perspective.

2024-06-06 | PXD049325 | Pride

Gene expression profiling of human atherosclerotic plaque

Project description:This SuperSeries is composed of the following subset Series: GSE23303: Gene expression profiling of human atherosclerotic plaque: Laser capture microscopy of smooth muscle cells and macrophages GSE23304: Gene expression profiling of human atherosclerotic plaque: 101 peripheral plaques GSE24495: Gene expression profiling of human atherosclerotic plaque: Carotid plaque GSE24702: Gene expression profiling of human atherosclerotic plaque: 290 peripheral plaques Refer to individual Series

2011-09-30 | E-GEOD-23314 | biostudies-arrayexpress

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model

Project description:Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model

| PRJNA554106 | ENA

Dental plaque

Project description:Dental plaque Genome sequencing

| PRJNA890880 | ENA

Target knockdown after systemic OTV administration in mice

Project description:Using single nucleus RNA sequencing, we knockdown of Malat1 across all cell types upon peripheral administration of OTV:Malat1.

2024-02-12 | GSE201741 | GEO

Gene expression profiling of human atherosclerotic plaque: Carotid plaque

Project description:In order to identify potential new biomarkers of atherosclerotic plaque composition we performed a large scale analysis of gene expression patterns in human atherosclerotic lesions. Whole genome expression analysis of 101 peripheral plaques identified a robust gene signature (1514 genes) dominated by inflammatory processes, and cholesterol metabolism and storage genes. Specific pathways enriched in this signature included activation of the Toll-like receptor signaling pathway, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction and lysosomal activity. Analysis of gene expression in plaque micro-dissected material revealed that the signature is strongly up-regulated in macrophage-rich regions and down-regulated in regions with high smooth muscle cell content. A smaller qPCR biomarker panel and inflammatory composite score (ICS) were developed to facilitate clinical translation of discoveries from gene expression profiling. We found that ICS correlates with histological features related to plaque vulnerability. In addition, ICS is able to separate groups of plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarerectomy. In summary, we identified a robust mRNA biomarker panel associated with histo-pathological as well as clinical hallmarks of vulnerable atherosclerotic plaque. This panel may be used as a diagnostic and prognostic tool in clinical setting to evaluate novel anti-atherosclerotic therapies. 6 human carotid plaques were sectioned in 1 mm thick slices. Alternative slices were used for gene expression profiling in Affymetrix/Merck custom 1.0 arrays (GPL10687), or for immunohistochemistry studies (CD68, Actin)

2011-09-30 | E-GEOD-24495 | biostudies-arrayexpress