Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice [spatial transcriptomics]

ABSTRACT: Peripheral inflammation has been associated with various neurodegeneration, including Alzheimer's Disease (AD). In this study, we employed an AD mouse model nasally infected with Staphylococcus aureus to assess the impact of chronic or acute peripheral inflammation on brain transcriptome and amyloid pathology. The chronic exposure increased the diffuse and compact amyloid plaques and blood cytokine levels. Following a short-term exposure, single-cell and spatial transcriptomics uncovered cell type- and spatial-specific transcriptional changes indicating a dysregulation of the brain barriers, including the blood-brain and the blood-cerebrospinal fluid barriers. Brain macrophages exhibited increased Apoe expression and macrophage-specific genes were upregulated at ventricular areas of infected mice. In addition, we report an increase of disease associated microglia genes around the A plaques, together with disbalances in neuronal expression in response to peripheral inflammation. Overall, results enlighten the mechanisms linking peripheral inflammation to AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE218360 | GEO | 2023/07/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice [scRNA-seq]

Project description:Peripheral inflammation has been associated with various neurodegeneration, including Alzheimer's Disease (AD). In this study, we employed an AD mouse model nasally infected with Staphylococcus aureus to assess the impact of chronic or acute peripheral inflammation on brain transcriptome and amyloid pathology. The chronic exposure increased the diffuse and compact amyloid plaques and blood cytokine levels. Following a short-term exposure, single-cell and spatial transcriptomics uncovered cell type- and spatial-specific transcriptional changes indicating a dysregulation of the brain barriers, including the blood-brain and the blood-cerebrospinal fluid barriers. Brain macrophages exhibited increased Apoe expression and macrophage-specific genes were upregulated at ventricular areas of infected mice. In addition, we report an increase of disease associated microglia genes around the A plaques, together with disbalances in neuronal expression in response to peripheral inflammation. Overall, results enlighten the mechanisms linking peripheral inflammation to AD.

2023-07-15 | GSE218352 | GEO

Multi-transcriptomics reveals brain cellular responses to peripheral infection in Alzheimer's disease model mice [RNA-seq]

2023-07-15 | GSE218346 | GEO

Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease

Project description:While complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here in an AD mouse model the transcriptional changes occurring in tissue domains of 100 μm diameter around the amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIG), while a multicellular gene co- expression network of Plaque-Induced Genes (PIGs) involving the complement system, oxidative stress, lysosomes and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomic analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.

2020-07-22 | GSE152506 | GEO

Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation

Project description:Alzheimer’s disease (AD) is characterized by neuroinflammation, accumulation of amyloid-β (Aβ) plaques and neuronal degeneration in the brain. The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset AD. ApoE interacts with complement regulator factor H (FH) but the role of this interaction in AD pathogenesis is unknown.

2023-05-03 | GSE193513 | GEO

Microglia - astrocyte cross-talk in the amyloid plaque niche of an Alzheimer’s disease mouse model as revealed by spatial transcriptomics (Stereo-seq Spatial Transcriptomics)

Project description:In this study, we characterize the transcriptomic alterations, cellular compositions, and signaling perturbations in the amyloid plaque niche in an AD mouse model using high-resolution spatial transcriptomics (CosMx and Stereo-seq). We discover a wide heterogeneity in the cellular composition of amyloid plaque niches, marked by an increase in microglial accumulation over time. We profile the alterations of glial cells as they are exposed to plaques, and conclude that the microglial response to plaques is consistent across different brain regions, while the astrocytic response is more heterogeneous. In turn, as the microglial density of plaque niches increases, astrocytes acquire a more neurotoxic phenotype and play a key role in inducing GABAergic signaling and decreasing glutamatergic signaling in neurons of the hippocampus. Taken together, we show that astrocytic signaling around plaque pathology is disrupted with increasing microglial density, which in turn induces an imbalance in synaptic signaling in neurons in the hippocampus.

2024-04-19 | GSE263789 | GEO

Peripherally-expressed apoE4 impairs brain functions and exacerbates amyloid pathogenesis by compromising cerebrovascular functions

Project description:The apolipoprotein E4 (APOE4) gene is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). ApoE is a lipid carrier abundantly expressed in both brain and periphery. As peripheral apoE is separated from brain apoE by the blood-brain barrier, it remains unclear whether peripheral apoE impacts brain functions and AD pathogenesis. To investigate this, we developed novel mouse models that conditionally express human APOE3 or APOE4 only in the liver with no detectable apoE in the brain. We found that liver-expressed apoE4 compromised synaptic plasticity and cognitive behaviors likely by impairing cerebrovascular functions. Remarkably, liver-expressed apoE4 exacerbated brain amyloid pathology, whereas apoE3 reduced it. Our findings demonstrate a pathogenic effect of peripheral apoE4, providing strong rationale for targeting peripheral apoE to treat AD.

2022-06-15 | GSE125501 | GEO

Distinct amyloid-b and tau associated microglia profiles in Alzheimer's disease

Project description:Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-b and intraneuronal hyperphosphorylated, tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-b and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-b plaques or both amyloid-b plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-b load and localized to amyloid-b plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with over tau pathology. This full characterization of human disease associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies.

2021-02-20 | GSE148822 | GEO

Spatiotemporal heterogeneity of inflammatory changes in Alzheimer's disease analyzed spatially resolved transcriptome

Project description:We investigated spatiotemporal molecular patterns related to AD pathophsiology using spatially resolved transcriptome of the AD mouse model. The late change of gray matters of AD was commonly related to neuroinflammation, while the early change in the white matter of AD represented neuronal projection and ensheathment of axons before the amyloid plaques accumulation. Disease-associated microglia and astrocyte signatures were spatially differently enriched. Our results provide a key spatiotemporally heterogeneous molecular change particularly related to inflammation in AD.

2024-01-10 | GSE174321 | GEO

The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Project description:Alzheimerâs disease (AD) is a neurodegenerative disease characterized by a marked decline in cognition and memory formation. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, namely the ones that are produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (AÎ²) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways that are relevant for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive AÎ² accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12 months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3 months, which became lower than WT at 5-6 and 11-12 months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3 months. Altogether, these findings provide new insights on a possible interplay between type I and type II IFN responses in AD and point to IFNs as mediators of cognitive decline in aging and in AD. The CP transcriptome of at least 3 mice of each age (3, 5-6 and 11-12 months) and of each genotype (WT or J20) was analyzed and compared.

2015-12-31 | E-GEOD-66598 | biostudies-arrayexpress

Autophagy restricts senescence and enables microglia to engage amyloid plagues in neuroprotection

Project description:Microglia are essential to maintain brain homeostasis, but when dysregulated, exert pathogenic functions in Alzheimer’s disease (AD). Recent evidence has implicated senescent/dystrophic microglia in the pathological process of AD. Whether microglial senescence is a cause or consequence of AD pathogenesis however is unclear. Here we report that autophagy, a lysosomal degradation pathway, restricts cellular senescence of microglia and confer neuroprotection in AD mouse model. Autophagy-deficient microglia show hallmarks of cellular senescence evidenced by reduced proliferation, increased Cdkn1a/p21Cip, dystrophy, and typical secretory phenotype. While disease-associated microglia (DAM) surrounding amyloid plaques exhibit heightened autophagy, autophagy deficient, senescent microglia (SAM) disengage from and thus fail to limit the diffusive amyloid plaques, causing enhanced tau phosphorylation and neurotoxicity in AD model. Treatment of senolytic drugs removes senescent microglia and alleviates neuropathology. Our study demonstrates a causal role of autophagy impairment in microglial senescence and neurotoxicity and suggests therapeutic potential of senolytic treatment for AD.

2023-04-24 | GSE192964 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data