Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alzheimer’s disease risk and the isoform dependence of phospholipid-apolipoprotein E interaction

ABSTRACT: The ε4 allele of the APOE gene, encoding the E4 isoform of apolipoprotein E, is the leading genetic risk factor for late-onset Alzheimer’s disease. While many potential mechanisms have been proposed to explain this risk, no dominant or unifying process has yet emerged. Here, we explore the primary function of apolipoprotein E in lipid transport and metabolism, by examining its lipid association properties, to establish whether they show isoform dependence and thereby could mediate Alzheimer’s risk. We focus on ethanolamine plasmalogen, a phospholipid subclass known to be depleted in Alzheimer’s disease brain.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Jenny Hallqvist

LAB HEAD: Kevin Mills

PROVIDER: PXD068681 | Pride | 2026-03-09

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Discovery_MSE_Identifications.txt	Txt
	JH_20220310_APOE_Screening_IP_01.raw.zip	Raw
	JH_20220310_APOE_Screening_IP_02.raw.zip	Raw
	JH_20220310_APOE_Screening_IP_03.raw.zip	Raw
	JH_20220310_APOE_Screening_IP_04.raw.zip	Raw

Items per page:

1 - 5 of 34

Similar Datasets

Microarray gene expression profiling of heart failure induced in apolipoprotein E-deficient mice by treatment with rosiglitazone

Project description:The anti-diabetic drug and agonist of the peroxisome proliferator-activated receptor gamma (Pparg), rosiglitazone, was recently withdrawn in many countries because the drug use was associated with an increased risk of heart failure. To investigate underlying pathomechanisms, we chose 6-month-old apolipoprotein E (apoE)-deficient mice, which are prone to atherosclerosis and insulin resistance, and thereby mimic the risk profile of patients with cardiovascular disease. After 8 weeks of rosiglitazone treatment (30 mg/kg/day), echocardiography and histology analyses demonstrated that rosiglitazone had induced heart failure with cardiac dilation. Concomitantly, cardiac lipid overload and lipid-induced cardiomyocyte death developed. The microarray gene expression study of heart tissue from rosiglitazone-treated apoE-deficient mice relative to untreated apoE-deficient mice and non-transgenic B6 mice identified cardiac Pparg-dependent lipid metabolism genes in rosiglitazone-treated mice, which seem to trigger a major heart failure promoting pathway. Microarray gene expression profiling was performed with heart tissue isolated from three study groups: (i) rosiglitazone-treated 8-month-old apolipoprotein (apoE)-deficient mice with symptoms of heart failure, (ii) untreated 8-month-old apoE-deficient mice, and (iii) age-matched, untreated, non-transgenic B6 control mice.

2011-03-18 | E-GEOD-28031 | biostudies-arrayexpress

LC-MS/MS analysis of NGF proteins purified from cerebrospinal fluid

Project description:The aim of the project is to develop and validate a new method to measure proNGF in the cerebrospinal fluid of living patients, and to use it as a biomarker of Alzheimer’s disease (AD). This method, a novel proNGF immunoassay, is based on molecular size separation by capillary electrophoresis and is performed with Simple Wes: this technique produces different immunoreactive peaks whose area can be calculated to search for a quantitative relation with AD. Our purpose was to confirm and validate by mass spectrometry analysis the presence of NGF in the selected peaks

2022-02-17 | PXD025883 | Pride

Convergent Cerebrospinal Fluid Proteomes and Metabolic Ontologies in Humans and Animal Models of Rett Syndrome

Project description:We measured the proteome of wild type and Mecp2 KO rat cerebral cortex, hippocampus and cerebrospinal fluid of animals aged 25 days postnatal age. We measured the proteome of human cerebrospinal fluid from Rett syndrome patients before and after treatment with recombinant IGF-1. We measured the proteome of wild type and Mecp2 KO as well as disease associated Mecp2 point mutations in LUHMEs dopaminergic postmitotic neurons. Project details can be found in doi: https://doi.org/10.1101/2021.11.30.470580

2022-10-14 | PXD030426 | Pride

Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation

Project description:Alzheimer’s disease (AD) is characterized by neuroinflammation, accumulation of amyloid-β (Aβ) plaques and neuronal degeneration in the brain. The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset AD. ApoE interacts with complement regulator factor H (FH) but the role of this interaction in AD pathogenesis is unknown.

2023-05-03 | GSE193513 | GEO

Detecting single amino acids and small peptides by combining isobaric tags and peptidomics

Project description:Single amino acids and small endogenous peptides play important roles in maintaining a properly functioning organism. These molecules are however currently only routinely identified in targeted approaches. In a small proof-of-concept mass spectrometry experiment we found that by combining isobaric tags and peptidomics, and by targeting singly charged molecules, we were able to identify a significant amount of single amino acids and small endogenous peptides using a basic mass-based identification approach. While there is still room for improvement, our simple test indicates that a limited amount of extra work when setting up the mass spectrometry experiment could potentially lead to a wealth of additional information.

2019-06-26 | PXD012872 | Pride

Single-cell RNA and TCR sequencing of IgG4-related disease cerebrospinal fluid

Project description:Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder signified by aberrant infiltration of IgG4-restricted plasma cells in a variety of organs. Clinical presentation is heterogeneous and pathophysiological mechanisms of IgG4-related autoimmunity remain elusive. Secondary parenchymal lesions of IgG4-RD in the central nervous system (CNS) are rare and there are very few cases of IgG4-RD with isolated CNS manifestation. Patients suffering from IgG4-RD frequently require prolonged treatment with glucocorticoids and are often unable to taper these medications. By leveraging single-cell sequencing of the cerebrospinal fluid (CSF) of a patient with an unusual inflammatory intracranial pseudotumor we provide novel insights into the immuno-pathophysiology of IgG4-RD by illustrating an IgG4-RD-associated polyclonal T cell response in the CSF and multifaceted cell-cell interaction between immune cell subsets and pathogenic B cells.

2021-06-19 | E-MTAB-10479 | biostudies-arrayexpress

Human astrocyte secretome data

Project description:In late-onset sporadic Alzheimer’s disease (AD), the most prevalent and strongest risk factor is the ε4 allele of the apolipoprotein E (APOE4). To investigate the pathophysiological effects of the APOE4 genotype in the human cellular context, we generated isogenic iPSC-derived astrocytes bearing APOE4 alleles from APOE3 control iPSC. Next, to identify astrocytic APOE4-specific secreted proteomes, we performed a mass spectrometry using culture media from human astrocytes carrying APOE3 or APOE4.

2023-09-01 | PXD044308 | JPOST Repository

Phospholipid composition of APOE lipoproteins affects microglia activation in an isoform-specific manner

Project description:Apolipoprotein E4 (APOE) is the strongest genetic risk factor for Alzheimer's disease (AD). Our lipidomic analysis identified a common phospholipid signature with a high level of correlation between APOEε3/3 and APOEε4/4 AD postmortem brain samples and native lipoproteins isolated from astrocyte conditioned media of mice expressing human APOE3 or APOE4. Behavioral testing demonstrated that native E3 lipoproteins were more effective than E4 at ameliorating the harmful effects of Aβ on cognition. We posit that APOE isoform-specific differences in the phospholipid composition of native lipoproteins prompt a differential microglial response. Using time-lapse in vivo two-photon imaging, we compared the effect of E3 or E4 infused with Aβ and determined that E3 lipoproteins induced a faster microglial migration towards Aβ. To determine how E3 and E4 lipoproteins affect microglial transcriptome in response to Aβ, we performed bulk and single cell RNA-seq of WT and Trem2ko mice. We show that compared to E4, cortical infusion of E3 lipoproteins upregulated a higher proportion of genes associated with an activated immune response accompanied by a downregulation of homeostatic genes. scRNA-seq identified microglia-specific clusters affected by Trem2 deficiency, suggesting that lack of Trem2 impairs the transition of microglia from homeostatic to an activated state. Compared to E3, E4-expressing microglia showed a reduced Aβ uptake that was additionally aggravated by Trem2 deficiency. Together, our findings have elucidated unique phenotypic and transcriptional differences in the microglial response to Aβ in the presence of E3 or E4 lipoproteins which could impact AD pathogenesis.

2021-04-30 | GSE158962 | GEO

Sleep deprivation leads to non-adaptive alterations in sleep microarchitecture and amyloid-β accumulation in a murine Alzheimer model

Project description:Impaired sleep is a common aspect of aging and often precedes the onset of Alzheimer's disease. Here, we compare the effects of sleep deprivation in young wild-type mice and their APP/PS1 littermates, a murine model of Alzheimer's disease. After 7 h of sleep deprivation, both genotypes exhibit an increase in EEG slow-wave activity. However, only the wild-type mice demonstrate an increase in the power of infraslow norepinephrine oscillations, which are characteristic of healthy non-rapid eye movement sleep. Notably, the APP/PS1 mice fail to enhance norepinephrine oscillations 24 h after sleep deprivation, coinciding with an accumulation of cerebral amyloid-β protein. Proteome analysis of cerebrospinal fluid and extracellular fluid further supports these findings by showing altered protein clearance in APP/PS1 mice. We propose that the suppression of infraslow norepinephrine oscillations following sleep deprivation contributes to increased vulnerability to sleep loss and heightens the risk of developing amyloid pathology in early stages of Alzheimer's disease.

2025-01-30 | PXD054763 | Pride

APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition

Project description:Compared to individuals carrying two copies of the ε4 allele of Apolipoprotein E (APOE), ε2 homozygotes have a ~99% reduction in late-onset Alzheimer’s disease (AD) risk. Here, we developed a transgenic mice model which allows for an inducible ‘switch’ between risk and protective alleles (APOE4s2). Gene expression and proteomic analyses confirm that APOE4s2 mice synthesize E4 at baseline and E2 after tamoxifen administration. A whole-body allelic switch results in a metabolic profile resembling E2/E2 humans and drives AD-relevant alterations in the lipidome and single-cell transcriptome, particularly in astrocytes.

2025-09-01 | GSE300079 | GEO