Summary of Study ST004168

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002628. The data can be accessed directly via it's Project DOI: 10.21228/M8ZC24 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST004168
Study TitleIntegrative brain omics approach highlights sn-1 lysophosphatidylethanolamine in Alzheimer's dementia
Study SummaryThe biology of individual lipid species and their relevance in Alzheimer’s disease (AD) remains incompletely understood. To explore the lipidomic biomarkers associated with cognition function and neuropathological changes in AD, we utilize non-targeted mass spectrometry on 316 post-mortem brains from participants in the Religious Orders Study (ROS) or Rush Memory and Aging Project (MAP) cohorts classified as control, asymptomatic AD (AAD), or symptomatic AD (SAD), and integrate the lipidomics data with untargeted proteomics from the same individuals. We find that lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) species are significantly lower in SAD than controls or AAD. Lipid-protein network analyses reveal that LPE/LPC modules are significantly associated with protein modules involved in MAPK/metabolism, post-synaptic density, and cell-ECM interaction pathways, and correlate with better antemortem cognition and reduced AD neuropathology. Particularly, LPE 22:6 [sn-1] is significantly decreased SAD and exerts a pronounced influence on protein changes relevant to neurotransmitter-driven post synaptic changes and plasticity compared to other lysophospholipids species. These findings suggest LPE 22:6 as a potential lipid signature and therapeutic target for AD.
Institute
Emory University
Last NameChen
First NameChih-Yu
Address1750 Haygood Dr. NE, Room N255, Atlanta, GA30322
Emailchih-yu.chen@emory.edu
Phone7653377809
Submit Date2025-08-01
Num Groups3
Total Subjects316
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2025-09-25
Release Version1
Chih-Yu Chen Chih-Yu Chen
https://dx.doi.org/10.21228/M8ZC24
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002628
Project DOI:doi: 10.21228/M8ZC24
Project Title:Integrative brain omics approach highlights sn-1 lysophosphatidylethanolamine in Alzheimer's dementia
Project Summary:The biology of individual lipid species and their relevance in Alzheimer’s disease (AD) remains incompletely understood. To explore the lipidomic biomarkers associated with cognition function and neuropathological changes in AD, we utilize non-targeted mass spectrometry on 316 post-mortem brains from participants in the Religious Orders Study (ROS) or Rush Memory and Aging Project (MAP) cohorts classified as control, asymptomatic AD (AAD), or symptomatic AD (SAD), and integrate the lipidomics data with untargeted proteomics from the same individuals. We find that lysophosphatidylethanolamine (LPE) and lysophosphatidylcholine (LPC) species are significantly lower in SAD than controls or AAD. Lipid-protein network analyses reveal that LPE/LPC modules are significantly associated with protein modules involved in MAPK/metabolism, post-synaptic density, and cell-ECM interaction pathways, and correlate with better antemortem cognition and reduced AD neuropathology. Particularly, LPE 22:6 [sn-1] is significantly decreased SAD and exerts a pronounced influence on protein changes relevant to neurotransmitter-driven post synaptic changes and plasticity compared to other lysophospholipids species. These findings suggest LPE 22:6 as a potential lipid signature and therapeutic target for AD.
Institute:Emory University
Laboratory:EILMC
Last Name:Chen
First Name:Chih-Yu
Address:1750 Haygood Dr. NE, Room N255, Atlanta, GA30322
Email:chih-yu.chen@emory.edu
Phone:7653377809

Subject:

Subject ID:SU004319
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Diagnosis Sample source
SA481371ROSMAP_73Asymptomatic AD Brain
SA481372ROSMAP_209Asymptomatic AD Brain
SA481373ROSMAP_122Asymptomatic AD Brain
SA481374ROSMAP_123Asymptomatic AD Brain
SA481375ROSMAP_208Asymptomatic AD Brain
SA481376ROSMAP_276Asymptomatic AD Brain
SA481377ROSMAP_77Asymptomatic AD Brain
SA481378ROSMAP_206Asymptomatic AD Brain
SA481379ROSMAP_202Asymptomatic AD Brain
SA481380ROSMAP_88Asymptomatic AD Brain
SA481381ROSMAP_71Asymptomatic AD Brain
SA481382ROSMAP_287Asymptomatic AD Brain
SA481383ROSMAP_289Asymptomatic AD Brain
SA481384ROSMAP_197Asymptomatic AD Brain
SA481385ROSMAP_65Asymptomatic AD Brain
SA481386ROSMAP_185Asymptomatic AD Brain
SA481387ROSMAP_134Asymptomatic AD Brain
SA481388ROSMAP_182Asymptomatic AD Brain
SA481389ROSMAP_211Asymptomatic AD Brain
SA481390ROSMAP_89Asymptomatic AD Brain
SA481391ROSMAP_307Asymptomatic AD Brain
SA481392ROSMAP_239Asymptomatic AD Brain
SA481393ROSMAP_110Asymptomatic AD Brain
SA481394ROSMAP_109Asymptomatic AD Brain
SA481395ROSMAP_108Asymptomatic AD Brain
SA481396ROSMAP_116Asymptomatic AD Brain
SA481397ROSMAP_230Asymptomatic AD Brain
SA481398ROSMAP_233Asymptomatic AD Brain
SA481399ROSMAP_213Asymptomatic AD Brain
SA481400ROSMAP_245Asymptomatic AD Brain
SA481401ROSMAP_262Asymptomatic AD Brain
SA481402ROSMAP_99Asymptomatic AD Brain
SA481403ROSMAP_246Asymptomatic AD Brain
SA481404ROSMAP_252Asymptomatic AD Brain
SA481405ROSMAP_118Asymptomatic AD Brain
SA481406ROSMAP_94Asymptomatic AD Brain
SA481407ROSMAP_258Asymptomatic AD Brain
SA481408ROSMAP_260Asymptomatic AD Brain
SA481409ROSMAP_119Asymptomatic AD Brain
SA481410ROSMAP_304Asymptomatic AD Brain
SA481411ROSMAP_177Asymptomatic AD Brain
SA481412ROSMAP_308Asymptomatic AD Brain
SA481413ROSMAP_368Asymptomatic AD Brain
SA481414ROSMAP_346Asymptomatic AD Brain
SA481415ROSMAP_169Asymptomatic AD Brain
SA481416ROSMAP_146Asymptomatic AD Brain
SA481417ROSMAP_360Asymptomatic AD Brain
SA481418ROSMAP_361Asymptomatic AD Brain
SA481419ROSMAP_22Asymptomatic AD Brain
SA481420ROSMAP_168Asymptomatic AD Brain
SA481421ROSMAP_366Asymptomatic AD Brain
SA481422ROSMAP_369Asymptomatic AD Brain
SA481423ROSMAP_143Asymptomatic AD Brain
SA481424ROSMAP_17Asymptomatic AD Brain
SA481425ROSMAP_379Asymptomatic AD Brain
SA481426ROSMAP_13Asymptomatic AD Brain
SA481427ROSMAP_10Asymptomatic AD Brain
SA481428ROSMAP_8Asymptomatic AD Brain
SA481429ROSMAP_381Asymptomatic AD Brain
SA481430ROSMAP_4Asymptomatic AD Brain
SA481431ROSMAP_153Asymptomatic AD Brain
SA481432ROSMAP_311Asymptomatic AD Brain
SA481433ROSMAP_340Asymptomatic AD Brain
SA481434ROSMAP_216Asymptomatic AD Brain
SA481435ROSMAP_324Asymptomatic AD Brain
SA481436ROSMAP_313Asymptomatic AD Brain
SA481437ROSMAP_314Asymptomatic AD Brain
SA481438ROSMAP_174Asymptomatic AD Brain
SA481439ROSMAP_47Asymptomatic AD Brain
SA481440ROSMAP_333Asymptomatic AD Brain
SA481441ROSMAP_317Asymptomatic AD Brain
SA481442ROSMAP_44Asymptomatic AD Brain
SA481443ROSMAP_39Asymptomatic AD Brain
SA481444ROSMAP_140Asymptomatic AD Brain
SA481445ROSMAP_36Asymptomatic AD Brain
SA481446ROSMAP_328Asymptomatic AD Brain
SA481447ROSMAP_331Asymptomatic AD Brain
SA481448ROSMAP_2Control Brain
SA481449ROSMAP_163Control Brain
SA481450ROSMAP_161Control Brain
SA481451ROSMAP_187Control Brain
SA481452ROSMAP_160Control Brain
SA481453ROSMAP_204Control Brain
SA481454ROSMAP_172Control Brain
SA481455ROSMAP_159Control Brain
SA481456ROSMAP_180Control Brain
SA481457ROSMAP_217Control Brain
SA481458ROSMAP_170Control Brain
SA481459ROSMAP_274Control Brain
SA481460ROSMAP_218Control Brain
SA481461ROSMAP_347Control Brain
SA481462ROSMAP_306Control Brain
SA481463ROSMAP_316Control Brain
SA481464ROSMAP_327Control Brain
SA481465ROSMAP_329Control Brain
SA481466ROSMAP_336Control Brain
SA481467ROSMAP_337Control Brain
SA481468ROSMAP_354Control Brain
SA481469ROSMAP_303Control Brain
SA481470ROSMAP_364Control Brain
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Collection:

Collection ID:CO004312
Collection Summary:Brain tissues were from the dorsolateral prefrontal cortex (DLPFC) from 316 subjects in the ROSMAP cohort studies of aging and dementia.
Sample Type:Brain

Treatment:

Treatment ID:TR004328
Treatment Summary:No treatment

Sample Preparation:

Sampleprep ID:SP004325
Sampleprep Summary:Approximately 50 mg of gray matter dissected from DLPFC were added to a 96-well plate with 250 µl PBS and 1.4 mm ceramic beads, and homogenized for 4.0 m/s for 20 sec at 4°C. After homogenization, the samples were centrifuged at 3220 x g for 10 min to pellet cell debris and the supernatant was extracted using a combination of Methyl tert-butyl ether (MTBE) and methanol using an automated sample handling manifold, Biotage Extrahera (Biotage, Uppsala, Sweden). For this, the homogenate was added to preconditioned 96-well plates, each well containing 10 µl internal standard obtained from Splash Lipidomix (Avanti Polar, Birmingham, AL). To each well, 200 µl methanol containing 50 µg/ml butylhydroxytoluene (BHT) was added. The sample was mixed by 3 up and down passes of the automated sample handling pipette arm. The samples were then centrifuged at 3220 x g for 10 minutes to pellet precipitated protein. The supernatant was then transferred to a separate deep well 96-well plate. To this, 250 µl MTBE:methanol (3:1 v/v) was added and mixed by 3 up and down passes. The sample plate was then centrifuged at 1000 x g for 3 minutes and the supernatant filtered through a 0.25 µm polytetrafluoroethylene (PFTE) filter plate (Biotage, ISOLUTE® FILTER+, Uppsala, Sweden). The extract was then dried under nitrogen for lipidomic analysis. Dried lipids were reconstituted in 200 μl 1:1 acetonitrile: isopropanol for LC-MS/MS analysis.
Processing Storage Conditions:-80℃
Extract Storage:4℃

Chromatography:

Chromatography ID:CH005255
Instrument Name:Thermo Vanquish
Column Name:Thermo Accucore C18 (100 x 4.6mm, 2.6um).
Column Temperature:40°C
Flow Gradient:0-0.2 min: 40% B; 0.2-1.5 min: 40-60% B; 1.5-6 min: 60-70% B; 6-9 min: 70-85% B; 9-11 min:85-100% B; 11-12.5 min: 100% B; 12.5-13 min:100-40% B; 13-16 min: 40% B
Flow Rate:0.4 ml/min
Solvent A:60% acetonitrile/40% water; 10 mM ammonium formate; 0.1% formic acid
Solvent B:10% acetonitrile/90% isopropanol; 10 mM ammonium formate; 0.1% formic acid
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN006919
Analysis Type:MS
Chromatography ID:CH005255
Num Factors:3
Num Metabolites:343
Units:peak area
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