Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

APOE3Christchurch modulates tau phosphorylation and β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases

ABSTRACT: APOE3Christchurch modulates tau phosphorylation and β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases

PROVIDER: PRJNA1008178 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25734158_1.fastq.gz	Fastqsanger.gz
	SRR25734158_2.fastq.gz	Fastqsanger.gz
	SRR25734159_1.fastq.gz	Fastqsanger.gz
	SRR25734159_2.fastq.gz	Fastqsanger.gz
	SRR25734160_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

APOE3Christchurch modulates tau phosphorylation and β-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer’s cases

Project description:Alzheimer’s disease (AD) is the most common cause of dementia. A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) was found to have extreme resistance to cognitive decline and tauopathy despite having high amyloid burden. We established induced pluripotent stem cell (iPS)-derived cerebral organoids from this resistant case and a non-protected control. We used CRISPR/Cas9 gene editing to remove or add APOE3Ch from these iPS cells to assess causality. We found a pattern of tau phosphorylation consistent with protection in APOE3Ch cerebral organoids. We identified Cadherin and Wnt signaling regulation by APOE3Ch through scRNA-sequencing and elevated β-catenin protein in APOE3Ch organoids as a potential mediator of protection against tauopathy. We have identified that ApoE3Ch acts as a Wnt signaling enhancer. Our study found that APOE3Ch is necessary and sufficient to confer resistance to tauopathy, a hallmark of AD. This establishes the premise for development of novel, protected case-inspired therapeutics for AD and tauopathies.

2024-03-20 | GSE241453 | GEO

Z-RNA drives Tau-mediated neurodegeneration of Alzheimer’s disease [RIP-Seq]

Project description:Tau aggregates lead to progressive neurodegeneration in Alzheimer’s disease (AD). Neuron death is one of the hallmarks of neurodegeneration.However, the pathological influence of neuronal death is undetermined, and the connection between Tau aggregates and neuronal death remains elusive. Here we demonstrated the essential role of neuron death in Tau-related neurodegeneration. Tau-neurons died in necroptosis, dependent on ZBP1 sensitized by Z-RNAs (an unusual left-handed conformation). Those endogenous Z-RNAs were transcripts of reactivated transposable elements (TEs) originally silenced in heterochromatin.

2023-11-22 | GSE248069 | GEO

Z-RNA drives Tau-mediated neurodegeneration of Alzheimer’s disease [lncRNA-Seq]

Project description:Tau aggregates lead to progressive neurodegeneration in Alzheimer’s disease (AD) (ref). Neuron death is one of the hallmarks of neurodegeneration (ref). However, the pathological influence of neuronal death is undetermined, and the connection between Tau aggregates and neuronal death remains elusive. Here we demonstrated the essential role of neuron death in Tau-related neurodegeneration. Tau-neurons died in necroptosis, dependent on ZBP1 sensitized by Z-RNAs (an unusual left-handed conformation). Those endogenous Z-RNAs were transcripts of reactivated transposable elements (TEs) originally silenced in heterochromatin.

2023-11-22 | GSE248068 | GEO

Z-RNA drives Tau-mediated neurodegeneration of Alzheimer’s disease [RNA-Seq]

2023-11-22 | GSE248067 | GEO

Z-RNA drives Tau-mediated neurodegeneration of Alzheimer’s disease

Project description:Z-RNA drives Tau-mediated neurodegeneration of Alzheimer’s disease

| PRJNA1041713 | ENA

Distinct tau neuropathology and cellular profiles of a APOE3 Christchurch homozygote protected against Autosomal Dominant Alzheimer’s dementia

Project description:We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer’s disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer’s symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant impacts the distribution of tau pathology, modulates age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.

2022-08-26 | GSE206744 | GEO

Increased G3BP2-Tau interaction in Tauopathies is a natural defense against Tau aggregation

Project description:Many RNA-binding proteins (RBPs), particularly those associated with RNA granules, promote pathological protein aggregation in neurodegenerative diseases. Here, we demonstrate that G3BP2, a core component of stress granules, directly interacts with Tau and inhibits Tau aggregation. In the human brain, the interaction of G3BP2 and Tau is dramatically increased in multiple Tauopathies and precedes neurofibrillary tangle (NFT) formation in Alzheimer’s disease (AD). Surprisingly, Tau pathology is significantly elevated upon loss of G3BP2 in human neurons and brain organoids. Moreover, we find that G3BP2 masks the microtubule-binding region (MTBR) of Tau, thereby inhibiting Tau aggregation. Our study defines a novel role for RBPs as a line of defense against Tau aggregation in Tauopathies.

2023-05-17 | GSE226624 | GEO

Tau molecular diversity mediates clinical heterogeneity in Alzheimer’s disease

Project description:Alzheimer’s disease (AD) causes unrelenting, progressive cognitive impairments, but its course is heterogeneous, with a broad range of rates of cognitive decline. The spread of tau aggregates (neurofibrillary tangles) across the cerebral cortex parallels symptom severity. We hypothesized that the kinetics of tau spread may vary if the properties of the propagating tau proteins varied across individuals. We carried out biochemical, biophysical, and both cell- and animal-based bioactivity assays, and mass spectrometry, to characterize tau in 32 AD patients. We found striking patient-to-patient heterogeneity in the hyperphosphorylated species of soluble, oligomeric, seed-competent tau. Tau seeding activity correlates with the aggressiveness of the clinical disease, and some post-translational modification sites appear to be associated with both enhanced seeding activity and worse clinical outcomes, while others are not. These data suggest that different individuals with “typical” AD may have distinct biochemical features of tau. These data are consistent with the possibility that individuals with AD, much like cancer patients, may have multiple molecular drivers of an otherwise common phenotype, and emphasizes the potential for personalized therapeutic approaches for slowing clinical progression in AD.

2020-08-09 | PXD018855 | Pride

The proto-oncogene DEK regulates neuronal excitability and tau accumulation in Alzheimer’s disease vulnerable neurons [RNA-seq_invitro]

Project description:Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease. We used a data-driven functional genomics approach to model ECII neurons in silico that led us to the prediction that the proto-oncogene DEK is a driver of tau pathology in these neurons. In order to understand the function of DEK in vulnerable neurons, we modulated its expression in ECII neurons in vitro and in vivo in the mouse. The present GEO entry includes all of the data we collected from DEK-silenced and DEK-overexpressing ECneurons in vitro and in vivo.

2022-05-22 | GSE203365 | GEO

The proto-oncogene DEK regulates neuronal excitability and tau accumulation in Alzheimer’s disease vulnerable neurons [RNA-seq_invivo]

Project description:Neurons from layer II of the entorhinal cortex (ECII) are the first to accumulate tau protein aggregates and degenerate during prodromal Alzheimer’s disease. We used a data-driven functional genomics approach to model ECII neurons in silico that led us to the prediction that the proto-oncogene DEK is a driver of tau pathology in these neurons. In order to understand the function of DEK in vulnerable neurons, we modulated its expression in ECII neurons in vitro and in vivo in the mouse. The present GEO entry corresponds to cell-type specific RNA-sequencing of ECII neurons in vivo 1 week after DEK silencing using AAV vectors.

2022-05-22 | GSE203366 | 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