Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA150875 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:There is accumulating evidence that amyloid beta and tau proteins may act synergistically to cause synapse and neural circuit degeneration in Alzheimer’s disease. In order to study this, we designed a new mouse model which lacks endogenous mouse tau, but expresses both the APP/PS1 transgene, which causes well-characterised plaque-associated synapse loss, and also reversibly expresses wild-type human tau (which can be suppressed with doxycycline). We examined the transcriptional changes in the frontal cortex of this mouse model, along with behaviour, pathology, synaptic plasticity, synapse degeneration and accumulation of amyloid beta and tau at synapses, and compared with littermate control genotypes: those lacking endogenous mouse tau, those lacking endogenous mouse tau but expressing the APP/PS1 transgene only, and those lacking endogenous mouse tau but reversibly expressing wild-type human tau only.
2019-11-12 | E-MTAB-7856 | biostudies-arrayexpress
Project description:In this study, using a microarray approach, we investigated the age-dependent changes in the gene expression profile of hippocampi obtained from young and old 3xTg-AD and WT control mice, in order to identify the molecular mechanisms involved in the development of AD and assess the role of aging in the development of the disease. A global gene expression profile in the hippocampi obtained from 3xTgAD (expressing mutant human APP, PS1, and tau) and WT mice at 3 and 12 months of age was studied by employing a Mouse OneArray Whole Genome DNA microarray. Data were analyzed with the Ingenuity Pathways Analysis (IPA) in order to achieve a classification of the results on the basis of their biological functions and disclose functional networks and/or pathways.
2012-06-28 | GSE35210 | GEO
Project description:Alzheimer’s disease (AD) is a common form of dementia characterized by amyloid plaque deposition, TAU pathology, neuroinflammation and neurodegeneration. Mouse models recapitulate some key features of AD. For instance, the B6.APP/PS1 model (carrying human transgenes for mutant forms of APP and PSEN1) shows plaque deposition and associated neuroinflammatory responses involving both astrocytes and microglia beginning around 6 months of age. However, in our colony, TAU pathology, significant neurodegeneration and cognitive decline are not apparent in this model even at older ages. Therefore, this model is ideal for studying neuroinflammatory responses to amyloid deposition. Here, RNA sequencing of brain and retinal tissue, generalized linear modeling (GLM), functional annotation followed by validation by immunofluorescence (IF) was performed in B6.APP/PS1 mice to determine the earliest molecular changes prior to and around the onset of plaque deposition (2-6 months of age).
2019-11-25 | GSE136861 | GEO
Project description:In this study, using a microarray approach, we investigated the age-dependent changes in the gene expression profile of hippocampi obtained from young and old 3xTg-AD and WT control mice, in order to identify the molecular mechanisms involved in the development of AD and assess the role of aging in the development of the disease. A global gene expression profile in the hippocampi obtained from 3xTgAD (expressing mutant human APP, PS1, and tau) and WT mice at 3 and 12 months of age was studied by employing a Mouse OneArray Whole Genome DNA microarray. Data were analyzed with the Ingenuity Pathways Analysis (IPA) in order to achieve a classification of the results on the basis of their biological functions and disclose functional networks and/or pathways. In this study we performed gene expression profiles for a total of 9 experiments. Hippocampi were collected from 2 3xTG and 2 WT mice at 3 months of age and from 2 3xTG and 2 WT mice at 12 months of age. Three MicroArray experiments were performed for each condition (WT 12 moa versus WT 3 moa; 3xTG 3 moa versus WT 3 moa; 3xTG 12 moa versus WT 12moa). On the total of 9 experiments 6 were biological replicates and 3 were technical replicates.
2012-06-27 | E-GEOD-35210 | biostudies-arrayexpress
Project description:In this study, we particularly focused on short ncRNA expression profiling of three, ten and twenty month old triple transgenic mouse model for Alzheimers disease (Oddo et al.; 2003;Neuron). These mice harbor presenilin PS1(M146V), APP(Swedish) and tau(P301L) mutations and develop beta-amyloid plaques and at later stages also a tau pathology. Controls are age matched B6129SF2/J mice.
2014-10-31 | E-MTAB-2738 | biostudies-arrayexpress
Project description:Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia, characterized by deposition of extracellular amyloid-beta (Aβ) aggregates and intraneuronal hyperphosphorylated Tau. Many AD risk genes, identified in genome-wide association studies (GWAS), are expressed in microglia, the innate immune cells of the central nervous system. Specific subtypes of microglia emerged in relation to AD pathology, such as disease-associated microglia (DAMs), which increased in number with age in amyloid mouse models and in human AD cases. However, the initial transcriptional changes in these microglia in response to amyloid are still unknown. Here, to determine early changes in microglia gene expression, hippocampal microglia from APPswe/PS1dE9 (APP/PS1) mice and wildtype littermates were isolated and analyzed by RNA sequencing (RNA-seq). By bulk RNA-seq, transcriptomic changes were detected in hippocampal microglia from 6-months-old APP/PS1 mice. By performing single cell RNA-seq of CD11c-positive and negative microglia from 6-months-old APP/PS1 mice and analysis of the transcriptional trajectory from homeostatic to CD11c-positive microglia, we identified a set of genes that potentally reflect the initial response of microglia to Aβ.
2024-04-01 | GSE226938 | GEO
Project description:Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia, characterized by deposition of extracellular amyloid-beta (Aβ) aggregates and intraneuronal hyperphosphorylated Tau. Many AD risk genes, identified in genome-wide association studies (GWAS), are expressed in microglia, the innate immune cells of the central nervous system. Specific subtypes of microglia emerged in relation to AD pathology, such as disease-associated microglia (DAMs), which increased in number with age in amyloid mouse models and in human AD cases. However, the initial transcriptional changes in these microglia in response to amyloid are still unknown. Here, to determine early changes in microglia gene expression, hippocampal microglia from APPswe/PS1dE9 (APP/PS1) mice and wildtype littermates were isolated and analyzed by RNA sequencing (RNA-seq). By bulk RNA-seq, transcriptomic changes were detected in hippocampal microglia from 6-months-old APP/PS1 mice. By performing single cell RNA-seq of CD11c-positive and negative microglia from 6-months-old APP/PS1 mice and analysis of the transcriptional trajectory from homeostatic to CD11c-positive microglia, we identified a set of genes that potentally reflect the initial response of microglia to Aβ.
2024-04-01 | GSE226937 | GEO
Project description:Bulk RNA-sequencing of astrocytes in the APP NL-F and APP PS1 models of ß-amyloidopathy, in which aspects of AD-related pathology progress at different speed, shows age-dependent gene expression changes. However, bulk RNA-seq does not provide insight into the heterogeneity of expression within this cell type, particularly relevant for such models, where reactive astrogliosis is most prominent in the vicinity of plaques. To investigate astrocyte heterogeneity in ß-amyloidopathy models, we thus performed single cell RNA-sequencing on astrocytes separated by FACS.
2024-03-21 | E-MTAB-13937 | biostudies-arrayexpress
Project description:Transgenic mouse models have been widely used to investigate the pathology of Alzheimer’s disease (AD). To elucidate underlying mechanisms of AD pathogenesis by amyloid beta (Aβ) and tau, we have generated a novel animal model of AD; ADLP - APT mice (Alzheimer’s Disease-Like Pathology) – carrying mutations of human amyloid precursor protein (APP), human presenilin-1 (PS1) and human tau. We profiled 9,824 proteins in the hippocampus of ADLP model mice using quantitative proteomics. To identify functional signatures in pathology of ADLP - APT mice, in-depth bioinformatics analysis was performed. For a longitudinal change of differentially expressed proteins (DEPs), we identified ADLP - APT mice hippocampal proteome in an age-dependent manner. Network maps of interactome between Aβ and tau in newly generated ADLP - APT mice reveal relationship between accelerated NFT pathology of AD and proteomic changes.
2018-01-25 | PXD006214 | Pride
Project description:Alzheimer’s disease (AD) is characterized by memory loss and neuropsychiatric symptoms associated with cerebral accumulation of amyloid-β (Aβ) and tau, but how memory and emotional neural circuits are disrupted by AD pathology remains unclear. Here, we investigated the transcriptional vulnerability of memory and emotional circuits to concomitant Aβ and tau pathologies in transgenic mice expressing mutant human amyloid precursor protein (APP) and Tau (APP/Tau mice) in excitatory neurons. At 9 months, we detected common and region-specific transcriptional responses in the hippocampus and basolateral amygdala (BLA) of APP/Tau mice, including astrocytic, microglia and 63 AD-associated genes. These findings suggest that Aβ and tau pathologies disrupt region-specific gene expression programs underlying vulnerability of memory and emotional circuits to AD neuropathology.
2025-02-07 | GSE279050 | GEO