Abeta levels in APP Tg mice with mixed genetic backgrounds
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE40330 | GEO | 2014/01/15
SECONDARY ACCESSION(S): PRJNA173543
REPOSITORIES: GEO
Similar Datasets
Project description:We combined a mouse model of Abeta accumulation and transcriptomics, and identified Klc1 as an Abeta accumulation modifier in vivo. For this transcriptomics analysis, we used 12 arrays (one mouse mRNA sample per array) for inbred mice analyses and 28 arrays for the APP Tg mice of mixed genetic backgrounds. First, 13309 probes whose signals were reliably detectable in all 40 arrays were selected from 25967 probes on the Illumina mouse Ref-8 Expression BeadChip. Second, to select the probes whose expression levels were affected by the DBA genetic background, we compared the expression levels of the 13309 probes in DBA, B6 and SJL inbred (non-Tg) mice (unpaired t-test).M-cM-^@M-^@Using inbred mice means that any change in gene expression is based on their genetic background, not the secondary effects of Abeta accumulation. To minimize the chance of false positives, we applied strict criteria in this selection: the fold change was equal to or more than 1.5 and the false discovery rate (FDR) was set to 0.001. In total 54 probes were identified, with the signals of 47 probes being lower and 7 probes being higher in DBA mice than those in either B6 or SJL. In the final step, we examined the correlation between the expression levels of these 54 probes and Abeta40 levels in the GuHCl fraction in APP Tg mice. Using strict selection criteria (PearsonM-bM-^@M-^Ys product-moment correlation FDR=0.001), we identified a total of four probes which correlated with Abeta levels. Two of these probes were higher in DBA and negatively correlated with the levels of Abeta accumulation. The other two probes were lower in DBA and positively correlated with the levels of Abeta accumulatio. Notably, the two probes (probe ID 4050133 and 6130468) that positively correlated with Abeta accumulation both detected the same transcript: kinesin light chain 1 (Klc1; also known as Kns2).
2014-01-15 | E-GEOD-40330 | biostudies-arrayexpress
Project description:Our previous work in a Drosophila model of Alzheimer's disease (AD) has shown that we can intervene into the pathways to slow or prevent AD progression. Lithium was able to rescue toxicity in the Drosophila AD model which corresponded with a reduction in Abeta levels. Furthermore, we have demonstrated that Lithium affects Abeta protein translation. To this end, we were interested in studying the effect of Lithium on Abeta using microarray analyses, to determine if we could uncover any interesting downstream pathways. Flies were expressing a mutant version of Abeta, the Arctic mutation, which increases the aggregation or production of Abeta (UAS-ArcAb42/+;elavGS/+). We collected flies 2 days post eclosion that either had no Arctic Abeta protein, or expressed Arctic with or without Lithium treatment for 17 days post eclosion. Samples were homogenised using RLT buffer with betamercaptoethanol.
2017-01-26 | E-MTAB-4611 | biostudies-arrayexpress
Project description:We report that local application of Abeta(1-42) for 24h triggers changes in the localized transcriptome, while the transcriptome in cell bodies remains largely unchanged. Axonal and somatic mRNA profiles of rat embryonic hippocampal neurons grown in microfluidic chambers were generated by RNA-Seq in duplicates using an Illumina MiSeq. Axons only were treated for 24 h with soluble oligomeric Abeta(1-42) or vehicle control.
2015-07-14 | E-GEOD-70860 | biostudies-arrayexpress
Project description:We report that local application of Abeta(1-42) for 24h triggers changes in the localized transcriptome, while the transcriptome in cell bodies remains largely unchanged.
2015-07-14 | GSE70860 | GEO
Project description:Oligomeric forms of amyloid-beta peptide (Abeta) are presumed to play a pivotal role in the pathogenesis of Alzheimer’s disease (AD). However, it is still unclear how Abeta oligomers contribute to AD pathogenesis in patient neural cells. We generated induced pluripotent stem cells (iPSCs) from a familial AD patient and differentiated them into neural cells. Abeta oligomers were accumulated in neural cells of AD bearing amyloid precursor protein (APP)-E693delta mutation. To uncover Abeta oligomers in AD(APP-E693delta) neural cells, we analyzed gene expression profiles of control and the AD neural cells
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Project description:We used TALEN editing to insert a direct expression cassette of either Abeta42 or Abeta 40 eliminating any requirement for amyloidogenic processing of APP to produce Abeta.
2018-12-31 | GSE119527 | GEO
Project description:Microglia activation is a hallmark in Alzheimer Disease. Non-active and Active microglia were isolated from young and aged WT mice and before- and after- pathology mouse models of Alzheimer Disease. Microarray analysis was used to determine the global gene expression programe in microglia during pathological (Abeta or TAU pathology) versus control state.
2021-03-03 | GSE129296 | GEO
Project description:Abnormal metal accumulation is associated with Alzheimer’s disease (AD) and has a relevant role in affecting amyloid beta-peptide (Abeta) aggregation and neurotoxicity.In the present study, employing a microarray analysis of 35,129 genes, we analyzed gene expression profile changes due to exposure to Abeta-Zn or Abeta-Cu complexes in neuronal-like cells (SH-SY5Y). Microarray data indicated that Abeta-Zn or Abeta-Cu complexes selectively alter expression of genes mainly related to cell death, inflammatory responses, and apoptosis.Taken together these findings indicate that Abeta-Zn or Abeta-Cu show some commonalities in affecting AD-related target functions. The overall modulatory activity on these genes supports the idea of a possible net result leading to mechanisms that counteract toxic effects of Abeta-Zn or Abeta-Cu.
2012-05-01 | GSE37661 | GEO
Project description:The organic anion transporter Adenosine triphosphate Binding Cassette subfamily C member 1 (ABCC1), also known as MRP1, has been demonstrated in murine models of Alzheimer's disease (AD) to export amyloid beta (Abeta) from the endothelial cells of the blood-brain barrier to the periphery, and that pharmaceutical activation of ABCC1 can reduce amyloid plaque deposition in the brain. Here, we show that ABCC1 is not only capable of exporting Abeta from the cytoplasm of human cells, but also that it's overexpression significantly reduces Abeta production and increases the ratio of alpha- versus beta-secretase mediated cleavage of the Amyloid Precursor Protein (APP), likely via indirect modulation of alpha-, beta-, and gamma-secretase activity.
2021-01-13 | GSE164642 | GEO
Project description:Accumulation of aggregated amyloid beta in the brain is believed to impair multiple cellular pathways and play a central role in Alzheimer disease pathology. But how this process is regulated remains unclear. In theory, measuring protein synthesis is the most direct way to evaluate a cell response to stimuli, but to date there have been few reliable methods to do this. To identify the protein regulatory network during the development of Abeta deposition in AD, we applied a new proteomic technique to quantitate newly synthesized protein (NSP) changes in the cerebral cortex and hippocampus of 2-, 5- and 9-month-old APP/PS1 AD transgenic mice. This bioorthogonal non-canonical amino acid tagging analysis combined PALM (Pulse Azidohomoalanine Labeling in Mammals) and HILAQ (Heavy Isotope Labeled AHA Quantitation) to reveal a comprehensive dataset of NSPs prior to and post Abeta deposition, including the identification of proteins not previously associated with AD, and demonstrated that the pattern of differentially expressed NSPs is age dependent. We also found dysregulated vesicle transportation networks including endosomal subunits, coat protein complex I (COPI) and mitochondrial respiratory chain throughout all time points and two brain regions. These results point to a pathological dysregulation of vesicle transportation that occurs prior to Abeta accumulation and the onset of AD symptoms, which may progressively impact the entire protein network and thereby drive neurodegeneration. This study illustrates key pathway regulation responses to the development of AD pathogenesis by directly measuring the changes in protein synthesis and provides unique insights into the mechanisms that underlie AD.
2020-10-03 | MSV000086234 | MassIVE