Summary of study ST001820

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001150. The data can be accessed directly via it's Project DOI: 10.21228/M82690 This work is supported by NIH grant, U2C- DK119886.


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Study IDST001820
Study TitleWT neurons treated with APOE3/3 and APOE4/4 ACM
Study SummaryWe performed a targeted lipidomic analysis on WT neurons treated with astrocyte conditioned media (ACM) from APOE3/3 or APOE4/4 astrocytes.
Columbia University
Last NameNuriel
First NameTal
Address630 W 168th St., P&S 12-430
Submit Date2021-06-02
Analysis Type DetailLC-MS
Release Date2021-06-10
Release Version1
Tal Nuriel Tal Nuriel application/zip

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Project ID:PR001150
Project DOI:doi: 10.21228/M82690
Project Title:APOE4-associated differences in lipidomics signatures in mouse brain and cultured neurons
Project Type:Lipidomics analysis
Project Summary:Apolipoprotein E ε4 (APOE4) is the primary genetic risk factor for the late-onset form of Alzheimer's disease (AD). Although the reason for this association is not completely understood, researchers have uncovered numerous effects of APOE4 expression on AD-relevant brain processes, including amyloid beta (Aβ) accumulation, lipid metabolism, endosomal-lysosomal processing and bioenergetics. In this study, we aimed to determine the effect of APOE4 allelic dosage on regional brain lipid composition in aged mice, as well as in cultured neurons. We performed a targeted lipidomic analysis on the entorhinal cortex (EC) and primary visual cortex (PVC) from 14–15 month-old APOE3/3, APOE3/4, and APOE4/4 targeted replacement mice, as well as on WT neurons cultured with conditioned media from APOE3/3 or APOE4/4 astrocytes. Our results reveal that the EC possesses increased susceptibility to APOE4-associated lipid alterations compared to the PVC. In the EC, APOE4 expression showed a dominant effect in decreasing diacylglycerol (DAG) levels, and a semi-dominant additive effect in the upregulation of multiple ceramide, glycosylated sphingolipid and bis(monoacylglycerol)phosphate (BMP) species, lipids known to accumulate as a result of endosomal-lysosomal dysfunction and defective lysosomal clearance. Neurons treated with conditioned media from APOE4 vs. APOE3 astrocytes also showed similar alterations of DAG and BMP species as those observed in the mouse EC. Our results suggest that APOE4 expression differentially modulates regional and neuronal lipid signatures, which may underlie the increased susceptibility of EC-localized neurons to AD pathology.
Institute:Columbia University
Last Name:Nuriel
First Name:Tal
Address:630 W 168th St., P&S 12-430