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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice

ABSTRACT: Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice

PROVIDER: PRJNA1126281 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29479530_1.fastq.gz	Fastqsanger.gz
	SRR29479530_2.fastq.gz	Fastqsanger.gz
	SRR29479531_1.fastq.gz	Fastqsanger.gz
	SRR29479531_2.fastq.gz	Fastqsanger.gz
	SRR29479673_1.fastq.gz	Fastqsanger.gz

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (Spatial Transcriptomics)

Project description:Unique microglial states have been identified in Alzheimer’s disease (AD) model mice and postmortem AD brains. Although it has been well documented that amyloid-β accumulation induces the alteration of microglial states, the relationship between tau pathology and microglial states remains incompletely understood because of a lack of suitable AD models. In the present study, we generated a novel AD model mouse by the intracerebral administration of tau purified from human brains with primary age-related tauopathy into AppNL-G-F/MAPT double knock-in (dKI) mice.

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (snRNA-seq, part 2)

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (snRNA-seq, part 1)

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (Spatial Transcriptomics)

Project description:Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (Spatial Transcriptomics)

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (snRNA-seq, part 1)

Project description:Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (snRNA-seq, part 1)

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (snRNA-seq, part 2)

Project description:Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice (snRNA-seq, part 2)

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Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy [snRNA-Seq]

Project description:Activation of microglia is a prominent pathological feature in tauopathies, including Alzheimer’s disease. How microglia activation contributes to tau toxicity remains largely unknown. Here we show that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, activated by tau, drives microglial-mediated tau propagation and toxicity. Constitutive activation of microglial NF-κB exacerbated, while inactivation diminished, tau seeding and spreading in young PS19 mice. Inhibition of NF-B activation enhanced the retention while reduced the release of internalized pathogenic tau fibrils from primary microglia and rescued microglial autophagy deficits. Remarkably, inhibition of microglial NF-κB in aged PS19 mice rescued tau-mediated learning and memory deficits, restored overall transcriptomic changes while increasing neuronal tau inclusions. Single cell RNA-seq revealed that tau-associated disease states in microglia were diminished by NF-B inactivation and further transformed by constitutive NF-B activation. Our study establishes a central role for microglial NF-B signaling in mediating tau spreading and toxicity in tauopathy.

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Tau accumulation induces microglial state alterations in Alzheimer’s disease model mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-12-15 | GSE270389 | GEO

Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy [bulk RNA-Seq]

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Microglial REV-ERBα regulates inflammation and lipid droplet formation to drive tauopathy

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2023-07-12 | GSE236875 | GEO

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