Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microglial microRNAs mediate sex-specific responses to tau pathology

ABSTRACT: Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by miRNAs, but it is unknown whether microglial miRNAs have sex-specific influences on disease. We show that microglial miRNA expression differs in males and females, and loss of miRNAs leads to sex-specific changes in the microglial transcriptome and to tau pathology. These findings suggest microglial miRNAs influence tau pathogenesis in a sex-specific manner.

ORGANISM(S): Mus musculus

PROVIDER: GSE122663 | GEO | 2019/11/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Microglial microRNAs mediate sex-specific responses to tau pathology

Project description:Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by miRNAs, but it is unknown whether microglial miRNAs have sex-specific influences on disease. We show that microglial miRNA expression differs in males and females, and loss of miRNAs leads to sex-specific changes in the microglial transcriptome and to tau pathology. These findings suggest microglial miRNAs influence tau pathogenesis in a sex-specific manner.

2019-11-05 | GSE135330 | GEO

Microglial microRNAs mediate sex-specific responses to tau pathology

Project description:Microglial microRNAs mediate sex-specific responses to tau pathology

| PRJNA505915 | ENA

Microglial microRNAs mediate sex-specific responses to tau pathology

Project description:Microglial microRNAs mediate sex-specific responses to tau pathology

| PRJNA558410 | ENA

Sex and life experience shape locus coeruleus pretangle tau pathology

Project description:The locus coeruleus (LC) is the earliest site of tau pathology in Alzheimer’s disease (AD), yet how modifiable environmental factors influence its vulnerability, particularly in a sex-specific manner, remains unclear. Using a rat model expressing pseudophosphorylated human tau (htauE14) in the LC, we show that tau accumulation induces anxiety-like behavior, cognitive deficits, and tau spread, shaped by sex and life history. Early-life enrichment attenuated tau propagation, reduced neuroinflammation, and increased hippocampal BDNF expression, while late enrichment reduced anxiety and improved learning. In contrast, late-life stress exacerbated LC degeneration. Single-nucleus RNA sequencing revealed female-biased transcriptional dysregulation in hippocampal excitatory neurons and glia cells following htauE14 expression. Environmental exposures drove distinct cell type-specific transcriptomic signatures: early stress further disrupted mitochondrial and synaptic programs, whereas early enrichment conferred transcriptional stability. These findings position the LC as a sexually dimorphic and environmentally sensitive node of early AD vulnerability and highlight the preventive potential of early-life interventions.

2026-03-18 | GSE306235 | GEO

Enhancing TREM2 expression activates microglia and modestly mitigates Tau pathology and neurodegeneration

Project description:TREM2, a microglia-specific receptor, is strongly associated with Alzheimer’s disease (AD) risk and modulates microglial responses critical to AD pathogenesis. However, its role in tauopathy and neurodegeneration remains unclear. Here, by using a PS19 tauopathy mouse model with inducible overexpression of human wild-type TREM2 (TREM2-WT) or the R47H variant (TREM2-R47H), we show that TREM2-WT overexpression modestly reduces soluble phosphorylated tau (p-tau) levels and mildly preserves neuronal integrity, whereas TREM2-R47H fails to impact p-tau levels or neurodegeneration. Single-cell RNA sequencing revealed that TREM2-WT enhances disease-associated microglia (DAM) signatures, while TREM2-R47H drives the MHCII+ microglial phenotypes. These findings demonstrate that TREM2-WT confers modest benefits in tauopathy models, whereas TREM2-R47H exhibits reduced functionality. Our study underscores the therapeutic potential of enhancing TREM2 activity to modulate microglial responses and mitigate neurodegeneration in AD.

2025-04-02 | GSE285713 | GEO

STING–IFN–CH25H lipid axis links innate immune activation to tau pathology [RNA-seq]

Project description:Genetic risk for Alzheimer’s disease is strongly enriched in pathways governing microglial activation and cholesterol metabolism, yet how these processes converge to drive neurodegeneration remains unclear. Here, we identify the oxysterol 25-hydroxycholesterol (25-HC) as a pathogenic lipid downstream of the cGAS-STING–IFN pathway. In models of tau pathology, interferon signaling induces Cholesterol 25-hydroxylase (CH25H) expression in microglia. Ch25h deletion in female P301S mice suppressed tau aggregation, preserved synapses, prevented brain atrophy, and rescued memory. Mechanistically, loss of CH25H disrupted STING trafficking, attenuated IFN activation, dampened self-perpetuating microglial inflammation. Strikingly, 25HC directly accelerated tau propagation in human iPSC derived neurons. It also disrupted lysosomal and mitochondrial lipid composition, driving cholesteryl ester accumulation and promoting apoptosis under tau-induced stress. These findings define a STING–IFN–CH25H lipid axis that bridges innate immune activation to tau pathology and toxicity, offering a tractable therapeutic pathway for inflammation-driven neurodegenerative conditions.

2025-12-09 | GSE313022 | GEO

STING–IFN–CH25H lipid axis links innate immune activation to tau pathology [scRNA-seq]

2025-12-09 | GSE313021 | GEO

APOE3-R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition

Project description:The Christchurch mutation (R136S) on the APOE3 (E3S/S) gene is associated with attenuation of tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high levels of amyloid beta pathology in the carrier. However, the specific molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse ApoE with wild-type human E3 or E3S/S on a tauopathy background. The R136S mutation markedly decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in theta and gamma powers. Additionally, the R136S mutation reduced interferon response to tau pathology in both mouse and human microglia, suppressing cGAS-STING activation. Treating tauopathy mice carrying wild-type E3 with a cGAS inhibitor protected against tau-induced synaptic loss and induced similar transcriptomic alterations to those induced by the R136S mutation across brain cell types. Thus, suppression of microglial cGAS-STING-IFN pathway plays a central role in mediating the protective effects of R136S against tauopathy.

2025-06-15 | GSE297721 | GEO

APOE3-R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition [bulk RNA-seq]

2025-06-15 | GSE297743 | GEO

Overexpressing low-density lipoprotein receptor reduces tau-associated neurodegeneration via apoE-dependent and independent mechanisms

Project description:APOE is the strongest genetic risk factor for late-onset Alzheimer’s disease. ApoE exacerbates tau-associated neurodegeneration by driving microglial activation. However, how apoE regulates microglial activation and whether targeting apoE is therapeutically beneficial in tauopathy is unclear. Here we show that overexpressing a low-density lipoprotein receptor (LDLR) transgene in P301S tau transgenic mice markedly reduces brain apoE and ameliorates tau pathology and neurodegeneration. ApoE specifically interacts with a high-molecular-weight tau species, and highly correlates with phospho-tau and insoluble tau levels. Microglial expression of the LDLR transgene reduces intracellular apoE and is associated with less microglial activation. snRNA-seq analysis of apoE-deficient or LDLR-overexpressing brains reveals that apoE deficiency drives microglial catabolism and increases the oligodendrocyte progenitor cell population. LDLR overexpression shares overlapping mechanisms, but uniquely upregulates microglial expression of specific ion channels and neurotransmitter receptors in tauopathy. A subset of disease-associated astrocytes with both neuroprotective and neurotoxic gene signatures is also identified.

2021-02-06 | GSE166261 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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