Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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

PROVIDER: PRJNA851960 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19792154_1.fastq.gz	Fastqsanger.gz
	SRR19792154_2.fastq.gz	Fastqsanger.gz
	SRR19792155_1.fastq.gz	Fastqsanger.gz
	SRR19792155_2.fastq.gz	Fastqsanger.gz
	SRR19792156_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

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

Distinct tau neuropathology and cellular profiles of an 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 may impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies.

| S-EPMC9381462 | biostudies-literature

Differential Neuropathology, Genetics, and Transcriptomics in two kindred cases with Alzheimer’s Disease and Lewy Body Dementia

Project description:Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two different forms of dementia but their pathology may involve the same cortical areas with overlapping cognitive manifestation. Dementia cases within the same family share a common genetic background. Nonetheless, the clinical phenotype may be different due to the different underlying molecular processes that come-up apart from genetics, causing diverse neurodegeneration. Through neuropathological, genetic and transcriptomic comparison of four different brain areas (substantia nigra, hippocampus, parietal lobe and basal ganglia), we defined commonalities and differences in the pathological processes of dementia in two kindred cases, a mother and a son, who developed a classical AD and an aggressive form of AD/LBD respectively. Genetic analysis did not reveal any pathogenic variants in the principal AD/LBD-causative genes. RNA sequencing highlighted high transcriptional dysregulation within the substantia nigra in LBD pathology, while AD underwent lower degree of transcriptional dysregulation, with the parietal lobe being the most involved brain area. Conversely, hippocampus (the most degenerated area) and basal ganglia (lacking specific lesions) expressed the lowest level of dysregulation. Our data suggest that there is a link between the transcriptional dysregulation and the amount of tissue damage accumulated across time, assessed through neuropathology. Moreover, we highlight that the molecular bases of AD and LBD follow very different pathways, which underlie their neuropathological signatures. Indeed, the transcriptome profiling through RNA sequencing may be an important tool in flanking the neuropathological analysis for a deeper understanding of AD and LBD pathogenesis.

2022-08-03 | GSE193438 | GEO

Cortex DNA methylation profiles for the Brains for Dementia research cohort

Project description:Genome-wide patterns of DNA methylation were quantified using the Illumina Infinium HumanMethylationEPIC BeadChip (“EPIC array”) in DNA samples isolated from cortex (dorsolateral prefrontal cortex and occipital cortex) for individuals with various amounts of dementia neuropathology.

2022-06-27 | GSE197305 | GEO

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

Differential Neuropathology, Genetics, and Transcriptomics in two kindred cases with Alzheimer’s Disease and Lewy Body Dementia

Project description:Differential Neuropathology, Genetics, and Transcriptomics in two kindred cases with Alzheimer’s Disease and Lewy Body Dementia

| PRJNA796229 | ENA

Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology

Project description:Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease. For the first (discovery) stage of our analysis, we used multiple tissues from donors (N = 122) archived in the MRC London Brainbank for Neurodegenerative Disease. From each donor, we isolated genomic DNA from four brain regions (EC, superior temporal gyrus (STG), prefrontal cortex (PFC) and CER) and, where available, from whole blood obtained pre-mortem. Our analyses focused on identifying differentially methylated positions (DMPs) associated with Braak staging, a standardized measure of neurofibrillary tangle burden determined at autopsy.

2014-08-17 | E-GEOD-59685 | biostudies-arrayexpress

Methylomic signatures of tau and beta amyloid in transgenic mouse models of Alzheimer’s disease neuropathology [RRBS]

Project description:We identified widespread DNA methylation changes associated with the development of both tau and amyloid neuropathology, including differentially methylated positions (DMPs) and regions (DMRs) at loci previously implicated in AD and overlapping changes identified in our ongoing analyses of human post-mortem AD brains.

2024-10-30 | GSE246560 | GEO

Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology

2014-08-17 | GSE59685 | GEO

Methylomic signatures of tau and beta amyloid in transgenic mouse models of Alzheimer’s disease neuropathology [HorvathMammalMethylChip40 Methylation Beadchip]

2024-10-30 | GSE246559 | GEO