Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA123155 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Expression profiling of laser-microdissected tissue from Tg2576 plaque-depositing mouse model of Alzheimer's disease
| PRJNA123153 | ENA
Project description:This study has investigated several parameters to obtain increased detection of the amyloid plaque intact protein profile, including a comparison of commonly used MALDI matrices, acid based reduction of signal suppression as well as the combination of strong acid based protein aggregate extraction from laser microdissection plaques to increase detection of proteoforms. Female APPPS1-21 transgenic mice were analyzed by MALDI Imaging with different matrices on a Ultraflextreme MALDI TOF/TOF instrument followed by data analysis in SCiLS Lab software. A combination of formic acid treatment of laser capture microdissected plaques was further utilized to expand the analysis and validation of amyloid plaques.
2021-03-25 | PXD009353 | Pride
Project description:While mouse models of ß-amyloidopathy recapitulate aspects of Alzheimer's disease pathology, including plaque formation and synapse loss, most progress at a speed such that outcomes are studied in the mature mouse, rather than the aged mouse. Here we investigated Aß-dependent changes to astrocytes in a knock-in model of ß-amyloidopathy (APP NL-F) that is known to progress more slowly.
2024-03-21 | E-MTAB-13936 | biostudies-arrayexpress
Project description:The e4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer's disease and has been shown to increase amyloid pathology relative to the presence of the e2 and e3 alleles. In the brain, apoE is primarily produced by astrocytes and under pathological conditions also by microglia. The cell-type-specific role of apoE in amyloid pathology, especially after amyloid plaque deposition, has not been fully elucidated. We generated APPPS1-21/Aldh1l1-Cre/ERT2/apoE4flox/flox and APPPS1-21/apoE4flox/flox mice. At 3.8-months-of-age, during the phase of rapid plaque growth, we administered tamoxifen to reduce astrocytic APOE4 and assessed mice at 6-months-of-age. One day before tamoxifen treatment, mice were injected with methoxy-X04, a blood-brain-barrier permeant fluorescent marker that labeled the pre-existing fibrillar amyloid plaques. By using this strategy, we were able to characterize pre-existing plaques prior to the loss of astrocytic APOE4 and to also analyze newly-formed amyloid plaques after the loss of astrocytic APOE4. Interestingly, astrocytic APOE4 deletion strongly reduced pre-existing plaques. It also prevented new plaque formation and decreased glial reactivity. Importantly, the removal of astrocytic APOE4 resulted in enhanced microglial and astrocytic phagocytic ability, which may contribute to the reduction of the amyloid pathology.
2021-09-30 | GSE183050 | GEO
Project description:Amyloid plaques (Aβ plaques) are one of the hallmarks of Alzheimer’s disease (AD). The main constituent of Aβ plaques is beta-amyloid peptides but a complex interplay of other infiltrating proteins also co-localizes. We focused on proteomic differences between Aβ plaques and adjacent control tissue in the transgenic mouse model of AD (APPPS1-21) and in similar regions from non-transgenic littermates. A microproteomic strategy included isolation of regions of interest by laser capture microdissection and analyzed by label-free liquid chromatography mass spectrometry. An in-solution digest protocol with a buffer containing an acid-labile surfactant was used to increase protein solubilization and protease efficiency.
2021-03-25 | PXD014274 | Pride
Project description:Liquid chromatography mass spectrometry was used to study tumor matrisome from laser capture microdissected FFPE tissue sections of human neck and squamous cell carcinoma (HnSCC) xenograft grown in mouse.
2023-10-21 | PXD033023 | Pride
Project description:It is well-established that women are disproportionately affected by Alzheimer’s disease (AD). The mechanisms underlying this sex-specific disparity are not fully understood, but several factors that are often associated-including interactions of sex hormones, genetic factors, and the gut microbiome-likely contribute to the disease's etiology. Here, we have examined the role of sex hormones and the gut microbiome in mediating A amyloidosis and neuroinflammation in APPPS1-21 mice. We report that postnatal gut microbiome perturbation in female APPPS1-21 mice leads to an elevation in levels of circulating estradiol. Early stage ovariectomy (OVX) leads to a reduction of plasma estradiol that is correlated with a significant alteration of gut microbiome composition and reduction in A pathology. On the other hand, supplementation of OVX-treated animals with estradiol restores A burden and influences gut microbiome composition. The reduction of A pathology with OVX is paralleled by diminished levels of plaque-associated MGnD-type microglia while estradiol supplementation of OVX-treated animals leads to a restoration of activated microglia around plaques. In summary, our investigation elucidates the complex interplay between sex-specific hormonal modulations, gut microbiome dynamics, metabolic perturbations, and microglial functionality in the pathogenesis of Alzheimer's disease.
2024-02-08 | GSE245831 | GEO
Project description:Alzheimer’s disease (AD) is the most comment type of dementia and is characterized by neuronal loss and cognitive decline. Aggregation and accumulation of Aβ proteoforms into senile plaques (SP) is one of the key hallmarks of the disease. The accumulation of Aβ in particular in hippocampus has been observed prior to cognitive decline, indicating a potential link between Aβ and the subsequent pathological events in AD. Several clinical trials have used immunotherapies targeting Aβ for degradation but have had diverging outcome in AD patients. We therefore set to determine the molecular profile of SP and surrounding tissue following biologics based immunotherapy using two antibodies, gantenerumab and aducanumab, that have high binding affinity to different Aβ epitopes for investigating the antibody Aβ-clearing properties. We used two cohorts of the APPPS1-21 PD mouse model that overexpresses human mutated APP (KM670/671NL) and PSEN1 (L166P). After chronic treatment for 4-month with weekly dose (20 and 10 mg/kg gantenerumab or aducanumab, respectively), we investigated SP load in two brain regions using thioflavin-S staining. A significant reduction of SP was observed in hippocampus of aducanumab treated mice while only a partial reduction was observed in same region of gantenerumab treated mice compared to respective control (irrelevant IgG and vehicle (PBS) treated mice). To determine the molecular changes associated with the aducanumab treatment, we applied two mass spectrometry (MS) methods, matrix-assisted laser desorption-ionization (MALDI) imaging, and microproteomics by combining laser microdissection and liquid chromatography-tandem MS (LC-MS/MS). We microdissected three subregions, containing SP, SP penumbra (SPP1), and an additional penumbra (SPP2) to the SPP1 extract from the hippocampus of the treated mice.
2021-03-25 | PXD021918 | Pride
Project description:Microglial dysfunction is a key pathological feature of Alzheimer´s disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their consequences for microglial function. Here, we performed an in-depth proteomic characterization of microglia in two AD mouse models, the overexpression APPPS1 and the knock-in AppNL-G-F (APP-KI) model. Proteome changes were followed from pre-deposition to early, middle and advanced stages of amyloid plaque pathology, revealing a large panel of Microglial Amyloid Response Proteins (MARPs) that reflect a heterogeneity of microglial alterations triggered by Adeposition. We demonstrate that the occurrence of MARPs coincided with the deposition of fibrillar A, recruitment of microglia to amyloid plaques and phagocytic dysfunction. While the proteomic and functional microglial changes were already markedly seen in 3 months old APPPS1 mice, they were delayed in the APP-KI model that generates substantially less fibrillar A. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy.
2020-06-09 | PXD016075 | Pride