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

Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice

Project description:The rare APOE3-Christchurch (APOE3Ch) variant is linked to resistance against PSEN1 p.E280A-driven autosomal dominant Alzheimer’s disease (AD). Recent studies in AD mouse models have demonstrated an effect of APOE3Ch in reducing tau pathology and tau propagation, yet its effects on amyloid pathology and related toxicity are not fully understood. While prior studies have reported reduced amyloid pathology with APOE3Ch, we extended this knowledge by investigating how astrocyte-specific expression of APOE3Ch impacts amyloid pathology and related responses in 5xFAD mice, an amyloid mouse model. Using adeno-associated virus (AAV)-mediated gene delivery, we overexpressed APOE3 or APOE3Ch in astrocytes of 5xFAD mice at the neonatal stage, then analyzed their effects during the advanced stage of amyloid pathology. Astrocytic APOE expression significantly reduced amyloid burden, neuritic dystrophy, and gliosis compared to GFP controls. Notably, astrocytic APOE3Ch expression, relative to APOE3, markedly lowered oligomeric Ab levels and promoted the formation of more compact, fibrillar plaques, suggesting a shift toward a less toxic aggregation profile. Transcriptomic profiling of cortical tissue revealed broad downregulation of immune-related and proteostatic pathways. These findings indicate that astrocytic APOE3Ch sufficiently attenuates Ab pathology and related toxicity, supporting its potential as a therapeutic modifier for AD.

2026-04-08 | GSE319850 | GEO

Microglial APOE3 Christchurch protects neurons through suppression of ferroptosis in a human iPSC-derived Alzheimer’s disease model

Project description:Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder characterized by extracellular amyloid plaque and neuronal tangle formation. A 2019 study discovered an association between the APOE3 Christchurch (APOE3Ch) variant and delayed AD progression in a PSEN1 mutation carrier. However, whether the APOE3Ch variant is causal to the delayed onset of AD and what is the underlying mechanism remains to be explored. In this study, we established neuron-microglia cocultures and neuroimmune organoids using CRISPR/Cas9-edited isogenic APOE3 and APOE3Ch microglia derived from human induced pluripotent stem cells (hiPSCs) along with PSEN1 mutant neurons or brain organoids. We show that APOE3Ch microglia exhibit enhanced phagocytic capacity and increased Tau clearance in neuron-microglia co-cultures. Moreover, APOE3Ch microglia were able to reduce phosphorylated Tau levels in PSEN1 mutant brain organoids. We also demonstrated that APOE3Ch microglia could preserve neural network activity in co-cultured PSEN1 neurons when challenged with synaptosomes prepared from AD patient brains. RNA-seq analysis identified phagocytosis and ferroptosis among pathways of differentially expressed genes from APOE3 and APOE3Ch microglia. Subsequent validation analyses established a causal link between reduced ferroptosis and enhanced phagocytosis including Tau clearance by APOE3Ch microglia, providing mechanistic insights into the neuroprotective role of APOE3Ch microglia. These findings together demonstrate that the APOE3Ch variant plays a causal role in microglial neuroprotection which can be exploited in therapeutic development for AD.

2024-12-27 | GSE240609 | GEO

Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice

Project description:Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice

| PRJNA1425310 | ENA

Plasma Extracellular Vesicles from PSEN1-E280A and APOE3 Christchurch patients

Project description:We isolated plasma EVs from MCI PSEN1E280A-APOE3 (n=10, mean age: 46, range 41-54), non-MCI PSEN1E280A-APOE3 (n=10, mean age: 34, range 22-48), and non-MCI PSEN1E280A-APOE3Ch (n=9, mean age: 35, range 16-51) participants, using differential centrifugation. EVs were characterized by nanoparticle tracking analysis, flow cytometry and LC-MS/MS analysis.

2026-02-02 | PXD068363 | Pride

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

Project description:We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

| S-EPMC6898984 | biostudies-literature

Microglial APOE3 Christchurch protects neurons through suppression of ferroptosis in a human iPSC-derived Alzheimer’s disease model

Project description:Microglial APOE3 Christchurch protects neurons through suppression of ferroptosis in a human iPSC-derived Alzheimer’s disease model

| PRJNA1004304 | ENA

Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease

Project description:Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease

| PRJNA801614 | ENA

Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection.

Project description:In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch.

| S-EPMC10041169 | biostudies-literature

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