Summary of Study ST004057

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 PR002547. The data can be accessed directly via it's Project DOI: 10.21228/M8DR87 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.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST004057
Study TitleMicroglial and Non-Microglial Regulation of Lipid Metabolism in Alzheimer's Revealed by Genetic and Pharmacological Depletion
Study SummaryAbnormal lipid metabolism is observed in Alzheimer’s disease (AD), but its contribution to disease progression remains unclear. Genetic studies indicate that microglia, the brain’s resident immune cells, influence lipid processing during AD. Here we show that, in both mouse models of AD and human postmortem brain tissue, microglia regulate the accumulation of specific lipids associated with disease pathology. Using multidimensional mass spectrometry-based shotgun lipidomics and histological analysis, we find that arachidonic acid-containing bis(monoacylglycero)phosphate (BMP) accumulates in response to amyloid plaques, and this buildup depends on microglial function and the AD risk gene progranulin (GRN). In contrast, lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) accumulate independently of microglia, instead associating with astrocyte activation and oxidative stress. These findings connect dysregulated lipid metabolism in AD to distinct brain cell types and molecular pathways. The results suggest that microglial regulation of lipid homeostasis is a potential therapeutic target for AD.
Institute
UT Health San Antonio
DepartmentDepartment of Medicine
LaboratoryXianlin Han Lab
Last NameHan
First NameXianlin
Address7703 Floyd Curl Drive
Emailhanx@uthscsa.edu
Phone2105624104
Submit Date2025-07-07
Raw Data AvailableYes
Raw Data File Type(s)mzML, raw(Thermo)
Analysis Type DetailMS(Dir. Inf.)
Release Date2025-08-14
Release Version1
Xianlin Han Xianlin Han
https://dx.doi.org/10.21228/M8DR87
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002547
Project DOI:doi: 10.21228/M8DR87
Project Title:Microglial and Non-Microglial Regulation of Lipid Metabolism in Alzheimer's Revealed by Genetic and Pharmacological Depletion
Project Summary:Abnormal lipid metabolism is observed in Alzheimer’s disease (AD), but its contribution to disease progression remains unclear. Genetic studies indicate that microglia, the brain’s resident immune cells, influence lipid processing during AD. Here we show that, in both mouse models of AD and human postmortem brain tissue, microglia regulate the accumulation of specific lipids associated with disease pathology. Using multidimensional mass spectrometry-based shotgun lipidomics and histological analysis, we find that arachidonic acid-containing bis(monoacylglycero)phosphate (BMP) accumulates in response to amyloid plaques, and this buildup depends on microglial function and the AD risk gene progranulin (GRN). In contrast, lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) accumulate independently of microglia, instead associating with astrocyte activation and oxidative stress. These findings connect dysregulated lipid metabolism in AD to distinct brain cell types and molecular pathways. The results suggest that microglial regulation of lipid homeostasis is a potential therapeutic target for AD.
Institute:UT Health San Antonio
Department:Department of Medicine
Laboratory:Xianlin Han Lab
Last Name:Han
First Name:Xianlin
Address:7703 Floyd Curl Drive
Email:hanx@uthscsa.edu
Phone:2105624104

Subject:

Subject ID:SU004203
Subject Type:Mammal
Subject Species:Homo sapiens; Mus musculus
Taxonomy ID:9606; 10090
Gender:Male and female

Factors:

Subject type: Mammal; Subject species: Homo sapiens; Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Subject_ID Treatment Subject Species Sex Sample source
SA469180LP_5xFAD-85xFAD OSD chow Mus musculus Female Cerebrum
SA469181G_5xFAD-35xFAD OSD chow Mus musculus Female Cerebrum
SA469182G_5xFAD-45xFAD OSD chow Mus musculus Female Cerebrum
SA469183LP_5xFAD-15xFAD OSD chow Mus musculus Female Cerebrum
SA469184LP_5xFAD-35xFAD OSD chow Mus musculus Female Cerebrum
SA469185LP_5xFAD-45xFAD OSD chow Mus musculus Female Cerebrum
SA469186LP_5xFAD-55xFAD OSD chow Mus musculus Female Cerebrum
SA469187LP_5xFAD-65xFAD OSD chow Mus musculus Female Cerebrum
SA469188LP_5xFAD-75xFAD OSD chow Mus musculus Female Cerebrum
SA469189SP_5xFAD-15xFAD OSD chow Mus musculus Female Cerebrum
SA469190G_5xFAD-15xFAD OSD chow Mus musculus Female Cerebrum
SA469191SP_5xFAD-25xFAD OSD chow Mus musculus Female Cerebrum
SA469192SP_5xFAD-35xFAD OSD chow Mus musculus Female Cerebrum
SA469193SP_5xFAD-45xFAD OSD chow Mus musculus Female Cerebrum
SA469194SP_5xFAD-55xFAD OSD chow Mus musculus Female Cerebrum
SA469195SP_5xFAD-65xFAD OSD chow Mus musculus Female Cerebrum
SA469196SP_5xFAD-75xFAD OSD chow Mus musculus Female Cerebrum
SA469197SP_5xFAD-85xFAD OSD chow Mus musculus Female Cerebrum
SA469198SP_5xFAD-95xFAD OSD chow Mus musculus Female Cerebrum
SA469199SP_5xFAD-105xFAD OSD chow Mus musculus Female Cerebrum
SA469200G_5xFAD-25xFAD OSD chow Mus musculus Female Cerebrum
SA469201LP_5xFAD-25xFAD OSD chow Mus musculus Female Cerebrum
SA469202G_5xFAD-65xFAD OSD chow Mus musculus Male Cerebrum
SA469203G_5xFAD-55xFAD OSD chow Mus musculus Male Cerebrum
SA469204G_5xFAD-75xFAD OSD chow Mus musculus Male Cerebrum
SA469205G_5xFAD-85xFAD OSD chow Mus musculus Male Cerebrum
SA469206LP_5xFAD+PLX5622-65xFAD PLX5622 Mus musculus Female Cerebrum
SA469207SP_5xFAD+PLX5622-25xFAD PLX5622 Mus musculus Female Cerebrum
SA469208LP_5xFAD+PLX5622-55xFAD PLX5622 Mus musculus Female Cerebrum
SA469209LP_5xFAD+PLX5622-45xFAD PLX5622 Mus musculus Female Cerebrum
SA469210LP_5xFAD+PLX5622-35xFAD PLX5622 Mus musculus Female Cerebrum
SA469211LP_5xFAD+PLX5622-25xFAD PLX5622 Mus musculus Female Cerebrum
SA469212LP_5xFAD+PLX5622-15xFAD PLX5622 Mus musculus Female Cerebrum
SA469213LP_5xFAD+PLX5622-85xFAD PLX5622 Mus musculus Female Cerebrum
SA469214SP_5xFAD+PLX5622-15xFAD PLX5622 Mus musculus Female Cerebrum
SA469215LP_5xFAD+PLX5622-75xFAD PLX5622 Mus musculus Female Cerebrum
SA469216SP_5xFAD+PLX5622-35xFAD PLX5622 Mus musculus Female Cerebrum
SA469217SP_5xFAD+PLX5622-55xFAD PLX5622 Mus musculus Female Cerebrum
SA469218SP_5xFAD+PLX5622-105xFAD PLX5622 Mus musculus Female Cerebrum
SA469219SP_5xFAD+PLX5622-95xFAD PLX5622 Mus musculus Female Cerebrum
SA469220SP_5xFAD+PLX5622-85xFAD PLX5622 Mus musculus Female Cerebrum
SA469221SP_5xFAD+PLX5622-75xFAD PLX5622 Mus musculus Female Cerebrum
SA469222SP_5xFAD+PLX5622-65xFAD PLX5622 Mus musculus Female Cerebrum
SA469223SP_5xFAD+PLX5622-45xFAD PLX5622 Mus musculus Female Cerebrum
SA469224G_5xFIRE-35xFIRE OSD chow Mus musculus Female Cerebrum
SA469225G_5xFIRE-25xFIRE OSD chow Mus musculus Female Cerebrum
SA469226G_5xFIRE-15xFIRE OSD chow Mus musculus Female Cerebrum
SA469227G_5xFIRE-45xFIRE OSD chow Mus musculus Male Cerebrum
SA469228G_5xFIRE-55xFIRE OSD chow Mus musculus Male Cerebrum
SA469229H_AD-8AD / Human Female Brodmann area 38
SA469230H_AD-10AD / Human Female Brodmann area 38
SA469231H_AD-3AD / Human Female Brodmann area 38
SA469232H_AD-6AD / Human Female Brodmann area 38
SA469233H_AD-1AD / Human Male Brodmann area 38
SA469234H_AD-9AD / Human Male Brodmann area 38
SA469235H_AD-7AD / Human Male Brodmann area 38
SA469236H_AD-5AD / Human Male Brodmann area 38
SA469237H_AD-4AD / Human Male Brodmann area 38
SA469238H_AD-2AD / Human Male Brodmann area 38
SA469239H_Control-9Control / Human Female Brodmann area 38
SA469240H_Control-5Control / Human Female Brodmann area 38
SA469241H_Control-3Control / Human Female Brodmann area 38
SA469242H_Control-10Control / Human Female Brodmann area 38
SA469243H_Control-8Control / Human Male Brodmann area 38
SA469244H_Control-7Control / Human Male Brodmann area 38
SA469245H_Control-4Control / Human Male Brodmann area 38
SA469246H_Control-6Control / Human Male Brodmann area 38
SA469247H_Control-1Control / Human Male Brodmann area 38
SA469248H_Control-2Control / Human Male Brodmann area 38
SA469249G_FIRE-2FIRE OSD chow Mus musculus Female Cerebrum
SA469250G_FIRE-1FIRE OSD chow Mus musculus Female Cerebrum
SA469251G_FIRE-3FIRE OSD chow Mus musculus Female Cerebrum
SA469252G_FIRE-4FIRE OSD chow Mus musculus Female Cerebrum
SA469253G_FIRE-5FIRE OSD chow Mus musculus Male Cerebrum
SA469254G_FIRE-6FIRE OSD chow Mus musculus Male Cerebrum
SA469255G_FIRE-7FIRE OSD chow Mus musculus Male Cerebrum
SA469256SP_Non-Tg-1Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469257LP_Non-Tg-1Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469258G_Non-Tg-3Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469259G_Non-Tg-2Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469260G_Non-Tg-1Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469261SP_Non-Tg-2Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469262G_Non-Tg-4Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469263LP_Non-Tg-2Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469264SP_Non-Tg-7Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469265LP_Non-Tg-4Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469266LP_Non-Tg-5Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469267SP_Non-Tg-10Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469268SP_Non-Tg-3Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469269SP_Non-Tg-4Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469270SP_Non-Tg-5Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469271LP_Non-Tg-3Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469272SP_Non-Tg-6Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469273SP_Non-Tg-9Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469274SP_Non-Tg-8Non-tansgenic OSD chow Mus musculus Female Cerebrum
SA469275G_Non-Tg-5Non-tansgenic OSD chow Mus musculus Male Cerebrum
SA469276G_Non-Tg-6Non-tansgenic OSD chow Mus musculus Male Cerebrum
SA469277G_Non-Tg-7Non-tansgenic OSD chow Mus musculus Male Cerebrum
SA469278G_Non-Tg-8Non-tansgenic OSD chow Mus musculus Male Cerebrum
SA469279SP_Non-Tg+PLX5622-8Non-tansgenic PLX5622 Mus musculus Female Cerebrum
Showing page 1 of 2     Results:    1  2  Next     Showing results 1 to 100 of 108

Collection:

Collection ID:CO004196
Collection Summary:This study includes lipidomic profiling of cerebrum from mouse models and BA-38 from postmortem human brain samples. Mouse right hemi-cerebra were dissected out, placed in cryotubes, and flash-frozen in liquid nitrogen. Human BA-38 samples were obtained from brain bank, received as frozon tissue. Frozen brains (both mice and human) were lyophilized using a benchtop freeze dryer (Labconco, Kansas City, MO, USA) under 0.5 vacuum for 48 hours. Lyophilized brain samples were weighted and transferred to Precellys 0.5 ml tubes pre-filled with small beads. Dried tissues were powdered using Precellys® Evolution Tissue Homogenizer (Bertin technologies, Montigny-le-Bretonneux, France) through one round of manufacture’s “soft program” at 0 °C. Powdered dry cerebrum tissues were weighted around 5mg for lipidomics using disposable anti-static spatulas. Dried and powdered tissues were homogenized in 0.1X PBS. Protein concentrations were measured using a bicinchoninic acid (BCA) assay.
Sample Type:Brain

Treatment:

Treatment ID:TR004212
Treatment Summary:5xFAD mice (Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax), were obtained from the Mutant Mouse Resource and Research Center (MMRRC) at The Jackson Laboratory in two different genetic backgrounds (B6SJL: MMRRC_034840-JAX; and C57BL6: MMRRC_034848-JAX). Mice were housed under 12/12 h light/dark cycles with free access to food and water ad libitum. Only female mice were used for the pharmacological (PLX5622-treated) partial microglial elimination cohorts and both male and female mice were used for the genetic (FIRE) full microglial elimination cohort. For the long-term pharmacological group, 1,200 mg of PLX5622 (free base)/kg was added to OpenStandard Diet (OSD) with 15 kcal% fat (Research diets, INC., New Brunswick, NJ, USA). Control mice were fed with OSD, and experimental mice with OSD+ PLX5622 from 6 weeks of age until 5 months when tissues were harvested. For the short-term pharmacological group, 1,200 mg of PLX5622 (free base)/kg was added to OpenStandard Diet (OSD) with 15 kcal% fat (Research diets, INC., New Brunswick, NJ, USA). Control mice were fed with OSD, and experimental mice with OSD+ PLX5622 from 6 weeks of age until 8 weeks when tissues were harvested.

Sample Preparation:

Sampleprep ID:SP004209
Sampleprep Summary:Lipid extraction from the homogenates, standardized by protein content, employed a modified Bligh and Dyer procedure with added internal standards. Lipid quantification was achieved using triple-quadrupole and orbitrap mass spectrometers (Thermo Fisher Scientific, Waltham, MA, USA), both coupled with a Nanomate device (Advion, Ithaca, NY, USA) and controlled by the Xcalibur system. Data processing, including ion peak selection, baseline correction, data transfer, peak intensity comparison 13C deisotoping, and quantitation, was facilitated by a custom-programmed Microsoft Excel macro as previously described, ensuring accurate analysis of lipid molecular species.

Chromatography:

Chromatography ID:CH005094
Instrument Name:none
Column Name:none
Column Temperature:none
Flow Gradient:none
Flow Rate:none
Solvent A:none
Solvent B:none
Chromatography Type:None (Direct infusion)

Analysis:

Analysis ID:AN006704
Analysis Type:MS
Chromatography ID:CH005094
Num Factors:14
Num Metabolites:118
Units:nmol/mg protein
  
Analysis ID:AN006705
Analysis Type:MS
Chromatography ID:CH005094
Num Factors:14
Num Metabolites:31
Units:nmol/mg protein
  
Analysis ID:AN006706
Analysis Type:MS
Chromatography ID:CH005094
Num Factors:14
Num Metabolites:133
Units:nmol/mg protein
  logo