Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer’s Disease fly models

ABSTRACT: Alzheimer's Disease (AD) is known for its profound impact on the brain, yet its systemic effects, particularly on peripheral tissues, remain underexplored. To address this gap, we utilized Drosophila, an established model for aging and neurodegeneration studies, to create the Alzheimer's Disease Fly Cell Atlas (AD-FCA). This comprehensive atlas comprises whole-organism single-nucleus transcriptomes from 219 cell types in two AD models, where adult flies express human Aβ42 or Tau exclusively in neurons. Our in-depth analyses reveal that Aβ42 prominently affects peripheral sensory neurons, whereas Tau expression leads to notable alterations in several non-neuronal tissues, including the gut, fat body, and reproductive system. The AD-FCA uncovers the nuanced interplay between neuronal pathology and peripheral tissue responses, offering novel insights into potential biomarkers and the systemic nature of AD.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE261656 | GEO | 2024/03/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Comparative gene expression profiling of Drosophila primary neuronal cultures expressing or not the human Tau0N4RWT protein

Project description:Deciphering the pathophysiological mechanisms that lead from the alteration of human Tau biology to neuronal death in tauopathies including Alzheimer's disease (AD), fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease (PiD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) depends notably on the identification of Tau cellular partners and a better understanding of Tau functions. In this aim, we performed gene expression profiling to identify upregulated and downregulated genes in response to ectopic induced expression for 3 days of human Tau0N4RWT protein in Drosophila primary neuronal cultures from Elav-GAL4GS larval brains.

2020-02-11 | E-MTAB-8712 | biostudies-arrayexpress

Phosphoproteomic analysis of brain form Alzheimer’s disease

Project description:Alzheimer's disease (AD), the most common neurodegenerative disorder caused by neuronal loss which results in memory loss. Formation of neurofibrillary tangles composed of abnormal hyper phosphorylation of tau protein is one of the major pathological hallmarks for AD. Several neurodegenerative disorders including AD are associated with abnormal protein phosphorylation events.

2021-09-08 | PXD010807 | Pride

Microglial response to Aβ and prostaglandin-E2 EP4 receptor activation

Project description:A persistent and non-resolving inflammatory response to accumulating Aβ peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating Aβ peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many pro-inflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing Aβ-induced inflammation represent a relatively unexplored area. Here we hypothesized that signaling through the prostaglandin-E2 (PGE2) EP4 receptor potently suppresses microglial inflammatory responses to Aβ42 peptides. In cultured microglial cells, EP4 stimulation attenuated levels of Aβ42-induced inflammatory factors and potentiated phagocytosis of Aβ42. Microarray analysis was performed and demonstrated that EP4 stimulation broadly opposed Aβ42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-κB transcription factors.

2014-04-25 | GSE55627 | GEO

RNA-Seq of human primary microglial cells treated with vehicle or human paired helical filaments (PHFs) purified from human tauopathy autopsy brain

Project description:Neuroinflammation is one of the major neuropathological hallmarks of Alzheimer's disease (AD) and related tauopathies. Activated microglia often co-exist in the same brain regions where tau protein accumulates as hyperphosphorylated and aggregated PHFs or neurofibrillary tangles (NFTs) within neurons in patients with AD and related tauopathies. However, the exact mechanisms how pathological tau could induce neuroinflammatory responses are not clear. In this study, we treated primary human microglia with purified human PHFs and performed RNA-sequence analysis.

2021-09-16 | E-MTAB-5742 | biostudies-arrayexpress

Proteomics of plasma exosomes reveals S100A8 as a novel biomarker for Alzheimer’s disease: a preliminary study

Project description:Levels of blood exosomal Aβ42, total Tau (t-Tau) and phosphorylated Tau (p-Tau) had a high correlation with their concentrations in cerebrospinal fluid (CSF), demonstrating that exosomal biomarkers have equal contribution as those in CSF for the diagnosis of AD. We aimed to comprehensively characterize the proteome of plasma exosomes to identify differentially expressed proteins (DEPs) and pathways in AD. Tandem mass tag (TMT) labeled quantitative proteomics was applied to analyze plasma exosomal proteins in 9 AD patients and 9 healthy controls.

2023-12-21 | PXD048063 | iProX

Alzheimer's Disease Dataset

Project description:FK506 binding protein 51kDa (FKBP51/FKBP5) is part of a mature heat shock protein 90kDa (Hsp90) chaperone complex that preserves tau. Microarray analysis of human brains reveal that FKBP51 gene expression selectively increased with age and Alzheimer's disease, which correlated with demethylation of the regulatory regions in the FKBP5 gene. Moreover, FKBP51 levels significantly correlated with Braak pathological staging. In addition, we show that in brains devoid of FKBP51, tau levels are reduced. Recombinant FKBP51 and Hsp90 synergize to block tau clearance through the proteasome and produce T22-positive tau oligomers. Overexpression of FKBP51 in a tau transgenic mouse model revealed that FKBP51 preserved tau species, including phosphorylated and oligomeric tau that have been linked to Alzheimer's disease pathogenesis. FKBP51 blocked amyloid formation and decreased tangle load in the brain. These alterations in tau turnover and aggregate structure culminated in enhanced neurotoxicity. We propose a model where age-associated increases in FKBP51 levels can out-compete the association of other pro-degradation Hsp90 co-chaperones, resulting in neurotoxic tau accumulation. Thus, strategies aimed at attenuating FKBP51 levels or its interaction with Hsp90 could be therapeutically relevant for Alzheimer's disease and other tauopathies. These AD cases were processed simultaneously with the control cases (young and aged) included in GSE11882 Postmortem brain tissue was collected from ADRC brain banks. Cases were preferentially selected where 3 or more brain regions were available

2014-04-21 | E-GEOD-48350 | biostudies-arrayexpress

Increased neutrophils in inflammatory bowel disease accelerate the accumulation of amyloid plaques in the mouse model of Alzheimer's disease

Project description:Alzheimer's disease (AD) is one of the neurodegenerative diseases and characterized by the appearance and accumulation of amyloid-β (Aβ) aggregates and phosphorylated tau with aging. We performed scRNAseq of immene cells in the brain from WT and AD mice.

2022-12-01 | GSE214747 | GEO

TREM2 haploinsufficiency impairs microglia’s response to injury and exacerbates tau pathology in a tauopathy mouse model [RNA-Seq]

Project description:Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis. The link between mutations in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a microglia-expressed gene, and the increased risk for developing late-onset AD suggests a detrimental role for microglia in disease pathophyioslogy. Hemizygous TREM2 mutations are posited to increase risk for AD through loss-of-function haploinsufficiency. The effects of TREM2 haploinsufficiency on tau pathology and tau-associated deficits have not yet been characterized. Using in vivo imaging, we showed that TREM2 haploinsufficiency, but not complete loss of TREM2, resulted in a striking agedependent impairment in microglia’s response to injury without affecting baseline motility. This TREM2-dependent effect on microglial motility is consistent with transcriptomic alterations in cell motility uncovered with unbiased RNAsequencing analysis. Moreover, TREM2 haploinsufficiency, but not complete loss of TREM2, exacerbated phosphorylated tau pathology in transgenic mice expressing mutant human tau. In addition, TREM2 haploinsufficiency increased tau inclusions and tau-mediated inflammation without further exacerbating neuronal loss. Our findings demonstrate for the first time that TREM2 haploinsufficiency induces deficits in a tauopathy mouse model, supporting the notion that the hemizygous missense variant results in loss-of-function.

2018-09-20 | GSE107293 | GEO

Stereotypic persistent B cell receptor clonotypes in Alzheimer’s Disease

Project description:The growing evidence suggest that the effect of Alzheimer’s Disease (AD) is not solely restricted to the brain. Numerous groups investigated the relation between the central nervous system and peripheral system, whereupon the peripheral system is closely involved in accordance with the progression of disease and systemic immunity. In our previous report, we identified shared B cell receptor (BCR) sequences among 10 AD patients which showed similar class-switching orientation, identical isotypes and high somatic hypermutation rate. For further investigation, we recruited 44 patients with AD at baseline and 37 patients for second follow-up to identify the shared BCR sequences among patients and persistent BCR within an individual patient. We were able to annotate 3983 unique AD specific BCR clonotypes and one of the clonotype showed binding affinity against human Aβ42 peptide. Our finding can provide evidence of common BCRs in AD patients exposed to antigenic stimulus which are related to AD pathogenesis.

2023-09-13 | GSE242738 | GEO

TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4

Project description:In addition to tau and Aβ pathologies, inflammation plays an important role in Alzheimer's disease (AD). Variants in APOE and TREM2 increase AD risk. ApoE4 exacerbates tau-linked neurodegeneration and inflammation in P301S tau mice and removal of microglia blocks tau-dependent neurodegeneration. Microglia adopt a heterogeneous population of transcriptomic states in response to pathology, at least some of which are dependent on TREM2. Previously, we reported that knockout (KO) of TREM2 attenuated neurodegeneration in P301S mice that express mouse Apoe. Because of the possible common pathway of ApoE and TREM2 in AD, we tested whether TREM2 KO (T2KO) would block neurodegeneration in P301S Tau mice expressing ApoE4 (TE4), similar to that observed with microglial depletion. Surprisingly, we observed exacerbated neurodegeneration and tau pathology in TE4-T2KO versus TE4 mice, despite decreased TREM2-dependent microgliosis. Our results suggest that tau pathology-dependent microgliosis, that is, TREM2-independent microgliosis, facilitates tau-mediated neurodegeneration in the presence of ApoE4.

2022-11-30 | GSE206368 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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