Project description:The amyloidogenic processing of APP to A-beta is known to play a central role in Alzheimer’s disease pathogenesis. Despite this, however, the physiological role of APP and its processing still remains elusive. In the current study we utilzed a transcriptional profiling approach, to determine the pathways that may become dysregulated in the brains of APPswe transgenic mice (Tg2576). As many pathways linked to Alzheimer’s disease are also linked to cholesterol metabolism, we also treated the Tg2576 mice with LXR agonist TO901317, to determine the effects of LXR agonists on the hippocampal transcriptome of Tg2576 mice. We used microarrays to identify gene expression modulated in hippocampus of transgenic TG2576 mice that express human APP containing the Swedish mutation and the transcriptional responses to treatment with an LXR agonist.
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from Tg2576 mice respect to age matched wild-type littermates (2 and 6 months of age).
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) respect to age matched wild-type (WT) littermates
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) respect to age matched wild-type (WT) littermates.
Project description:Olfaction is often deregulated in Alzheimer's disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from Tg2576 mice (2, and 6 months of age) respect to age-matched wild-type (WT) littermates.
Project description:MicroRNAs influence restorative physiological or degenerative pathological processes in several neurological disorders, yet their role in Alzheimer’s disease remains unclear. Here we compared microRNAs expression in the period of AD pathogenesis when mice first begin to have detectable extracellular Aβ deposition. Tg2576 mice aged 9-10 months and their wild type littermates, as well as a double transgenic model of AD, APP/ PS1M146V/+ and wild type C57BL/6J mice both at 3-4 age months (n=3) were used. Hippocampus tissue miRNAs were detected by hybridization to microarrays having 924 mammalian miRNA probes.The result indicated that some of the deregulated miRNAs in AD mice have been implicated in amyloid beta production.
Project description:MicroRNAs influence restorative physiological or degenerative pathological processes in several neurological disorders, yet their role in AlzheimerM-bM-^@M-^Ys disease remains unclear. Here we compared microRNAs expression in the period of AD pathogenesis when mice first begin to have detectable extracellular AM-NM-2 deposition. Tg2576 mice aged 9-10 months and their wild type littermates, as well as a double transgenic model of AD, APP/ PS1M146V/+ and wild type C57BL/6J mice both at 3-4 age months (n=3) were used. Hippocampus tissue miRNAs were detected by hybridization to microarrays having 924 mammalian miRNA probes.The result indicated that some of the deregulated miRNAs in AD mice have been implicated in amyloid beta production. AD mice vs. control mice
Project description:The purpose of this project was to compare whole genome expression in 5 transgenic mice with human genes for dementia that result in either plaques or tangle pathology to the expression in wild-type control mice and to each other at different stages of disease progression. Total RNA was obtained from hippocampus, cortex and cerebellum in four lines of ‘amyloid’ transgenic mice (mutant human APP and APP/PSEN1 genes) and ‘TAU’ transgenic mice (mutant human MAPT gene) as well as wild-type control mice at 8,16, 32 and 72 weeks
Project description:We assessed astrocyte diversity in the cortex, hippocampus, and striatum using sing cell RNA-seq (scRNA-seq). We also assessed cortical astrocytes in wild type control and transgenic APP/PS1dE9 mice using scRNA-seq.
Project description:Brain samples (left hippocampus) from APP/PS1 transgenic mice and wild-type littermate at 15-months were processed for simultaneous coding and non-coding RNA-Seq analysis using a novel RNA-Seq protocol. These data were then analyzed for differential expression.