Summary of Study ST002453
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 PR001580. The data can be accessed directly via it's Project DOI: 10.21228/M8G711 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.
Study ID | ST002453 |
Study Title | APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge (Part 3 of 3) |
Study Summary | The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNAseq highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic, while spatial transcriptomics and MALDI mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism. |
Institute | University of Kentucky |
Department | Physiology |
Laboratory | Lance Johnson; Josh Morganti |
Last Name | Devanney |
First Name | Nicholas |
Address | Physiology, 760 Press Ave, Healthy Kentucky Research Bldg, Rm152, Lexington, Kentucky, 40508, USA |
Nicholas.Devanney@uky.edu | |
Phone | 8593238083 |
Submit Date | 2022-11-14 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Waters) |
Analysis Type Detail | MALDI-MS |
Release Date | 2023-01-25 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
mb_sample_id | local_sample_id | Brain Region | Group | APOE genotype | 5XFAD Genotype | Age |
---|---|---|---|---|---|---|
SA245312 | JJ3_73_Cerebral Nuclei | Cerebral Nuclei | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245313 | JJ3_76_Cerebral Nuclei | Cerebral Nuclei | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245314 | JJ3_66_Cerebral Nuclei | Cerebral Nuclei | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245315 | B427_Cerebral Nuclei | Cerebral Nuclei | E3_old | E3/E3 | Wild-type | 24 months |
SA245316 | B354_Cerebral Nuclei | Cerebral Nuclei | E3_old | E3/E3 | Wild-type | 24 months |
SA245317 | B425_Cerebral Nuclei | Cerebral Nuclei | E3_old | E3/E3 | Wild-type | 24 months |
SA245318 | B647_Cerebral Nuclei | Cerebral Nuclei | E3_young | E3/E3 | Wild-type | 3 months |
SA245319 | B648_Cerebral Nuclei | Cerebral Nuclei | E3_young | E3/E3 | Wild-type | 3 months |
SA245320 | B652_Cerebral Nuclei | Cerebral Nuclei | E3_young | E3/E3 | Wild-type | 3 months |
SA245321 | KK4_116_Cerebral Nuclei | Cerebral Nuclei | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245322 | KK4_96_Cerebral Nuclei | Cerebral Nuclei | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245323 | KK4_40_Cerebral Nuclei | Cerebral Nuclei | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245324 | C202_Cerebral Nuclei | Cerebral Nuclei | E4_old | E4/E4 | Wild-type | 24 months |
SA245325 | C384_Cerebral Nuclei | Cerebral Nuclei | E4_old | E4/E4 | Wild-type | 24 months |
SA245326 | C362_Cerebral Nuclei | Cerebral Nuclei | E4_old | E4/E4 | Wild-type | 24 months |
SA245327 | C763_Cerebral Nuclei | Cerebral Nuclei | E4_young | E4/E4 | Wild-type | 3 months |
SA245328 | C762_Cerebral Nuclei | Cerebral Nuclei | E4_young | E4/E4 | Wild-type | 3 months |
SA245329 | C761_Cerebral Nuclei | Cerebral Nuclei | E4_young | E4/E4 | Wild-type | 3 months |
SA245330 | JJ3_73_Cortical Subplate | Cortical Subplate | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245331 | JJ3_76_Cortical Subplate | Cortical Subplate | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245332 | JJ3_66_Cortical Subplate | Cortical Subplate | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245333 | B425_Cortical Subplate | Cortical Subplate | E3_old | E3/E3 | Wild-type | 24 months |
SA245334 | B354_Cortical Subplate | Cortical Subplate | E3_old | E3/E3 | Wild-type | 24 months |
SA245335 | B427_Cortical Subplate | Cortical Subplate | E3_old | E3/E3 | Wild-type | 24 months |
SA245336 | B647_Cortical Subplate | Cortical Subplate | E3_young | E3/E3 | Wild-type | 3 months |
SA245337 | B648_Cortical Subplate | Cortical Subplate | E3_young | E3/E3 | Wild-type | 3 months |
SA245338 | B652_Cortical Subplate | Cortical Subplate | E3_young | E3/E3 | Wild-type | 3 months |
SA245339 | KK4_96_Cortical Subplate | Cortical Subplate | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245340 | KK4_116_Cortical Subplate | Cortical Subplate | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245341 | KK4_40_Cortical Subplate | Cortical Subplate | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245342 | C202_Cortical Subplate | Cortical Subplate | E4_old | E4/E4 | Wild-type | 24 months |
SA245343 | C362_Cortical Subplate | Cortical Subplate | E4_old | E4/E4 | Wild-type | 24 months |
SA245344 | C384_Cortical Subplate | Cortical Subplate | E4_old | E4/E4 | Wild-type | 24 months |
SA245345 | C763_Cortical Subplate | Cortical Subplate | E4_young | E4/E4 | Wild-type | 3 months |
SA245346 | C762_Cortical Subplate | Cortical Subplate | E4_young | E4/E4 | Wild-type | 3 months |
SA245347 | C761_Cortical Subplate | Cortical Subplate | E4_young | E4/E4 | Wild-type | 3 months |
SA245348 | JJ3_66_Fiber Tracts | Fiber Tracts | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245349 | JJ3_73_Fiber Tracts | Fiber Tracts | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245350 | JJ3_76_Fiber Tracts | Fiber Tracts | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245351 | B427_Fiber Tracts | Fiber Tracts | E3_old | E3/E3 | Wild-type | 24 months |
SA245352 | B425_Fiber Tracts | Fiber Tracts | E3_old | E3/E3 | Wild-type | 24 months |
SA245353 | B354_Fiber Tracts | Fiber Tracts | E3_old | E3/E3 | Wild-type | 24 months |
SA245354 | B648_Fiber Tracts | Fiber Tracts | E3_young | E3/E3 | Wild-type | 3 months |
SA245355 | B647_Fiber Tracts | Fiber Tracts | E3_young | E3/E3 | Wild-type | 3 months |
SA245356 | B652_Fiber Tracts | Fiber Tracts | E3_young | E3/E3 | Wild-type | 3 months |
SA245357 | KK4_40_Fiber Tracts | Fiber Tracts | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245358 | KK4_116_Fiber Tracts | Fiber Tracts | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245359 | KK4_96_Fiber Tracts | Fiber Tracts | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245360 | C384_Fiber Tracts | Fiber Tracts | E4_old | E4/E4 | Wild-type | 24 months |
SA245361 | C202_Fiber Tracts | Fiber Tracts | E4_old | E4/E4 | Wild-type | 24 months |
SA245362 | C362_Fiber Tracts | Fiber Tracts | E4_old | E4/E4 | Wild-type | 24 months |
SA245363 | C762_Fiber Tracts | Fiber Tracts | E4_young | E4/E4 | Wild-type | 3 months |
SA245364 | C763_Fiber Tracts | Fiber Tracts | E4_young | E4/E4 | Wild-type | 3 months |
SA245365 | C761_Fiber Tracts | Fiber Tracts | E4_young | E4/E4 | Wild-type | 3 months |
SA245366 | JJ3_66_Hippocampus | Hippocampus | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245367 | JJ3_73_Hippocampus | Hippocampus | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245368 | JJ3_76_Hippocampus | Hippocampus | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245369 | B425_Hippocampus | Hippocampus | E3_old | E3/E3 | Wild-type | 24 months |
SA245370 | B354_Hippocampus | Hippocampus | E3_old | E3/E3 | Wild-type | 24 months |
SA245371 | B427_Hippocampus | Hippocampus | E3_old | E3/E3 | Wild-type | 24 months |
SA245372 | B652_Hippocampus | Hippocampus | E3_young | E3/E3 | Wild-type | 3 months |
SA245373 | B647_Hippocampus | Hippocampus | E3_young | E3/E3 | Wild-type | 3 months |
SA245374 | B648_Hippocampus | Hippocampus | E3_young | E3/E3 | Wild-type | 3 months |
SA245375 | KK4_116_Hippocampus | Hippocampus | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245376 | KK4_96_Hippocampus | Hippocampus | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245377 | KK4_40_Hippocampus | Hippocampus | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245378 | C384_Hippocampus | Hippocampus | E4_old | E4/E4 | Wild-type | 24 months |
SA245379 | C202_Hippocampus | Hippocampus | E4_old | E4/E4 | Wild-type | 24 months |
SA245380 | C362_Hippocampus | Hippocampus | E4_old | E4/E4 | Wild-type | 24 months |
SA245381 | C761_Hippocampus | Hippocampus | E4_young | E4/E4 | Wild-type | 3 months |
SA245382 | C762_Hippocampus | Hippocampus | E4_young | E4/E4 | Wild-type | 3 months |
SA245383 | C763_Hippocampus | Hippocampus | E4_young | E4/E4 | Wild-type | 3 months |
SA245384 | JJ3_76_Hypothalamus | Hypothalamus | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245385 | JJ3_73_Hypothalamus | Hypothalamus | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245386 | JJ3_66_Hypothalamus | Hypothalamus | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245387 | B425_Hypothalamus | Hypothalamus | E3_old | E3/E3 | Wild-type | 24 months |
SA245388 | B354_Hypothalamus | Hypothalamus | E3_old | E3/E3 | Wild-type | 24 months |
SA245389 | B427_Hypothalamus | Hypothalamus | E3_old | E3/E3 | Wild-type | 24 months |
SA245390 | B647_Hypothalamus | Hypothalamus | E3_young | E3/E3 | Wild-type | 3 months |
SA245391 | B648_Hypothalamus | Hypothalamus | E3_young | E3/E3 | Wild-type | 3 months |
SA245392 | B652_Hypothalamus | Hypothalamus | E3_young | E3/E3 | Wild-type | 3 months |
SA245393 | KK4_116_Hypothalamus | Hypothalamus | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245394 | KK4_96_Hypothalamus | Hypothalamus | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245395 | KK4_40_Hypothalamus | Hypothalamus | E4_FAD | E4/E4 | Hemizygous | 12 months |
SA245396 | C384_Hypothalamus | Hypothalamus | E4_old | E4/E4 | Wild-type | 24 months |
SA245397 | C202_Hypothalamus | Hypothalamus | E4_old | E4/E4 | Wild-type | 24 months |
SA245398 | C362_Hypothalamus | Hypothalamus | E4_old | E4/E4 | Wild-type | 24 months |
SA245399 | C763_Hypothalamus | Hypothalamus | E4_young | E4/E4 | Wild-type | 3 months |
SA245400 | C761_Hypothalamus | Hypothalamus | E4_young | E4/E4 | Wild-type | 3 months |
SA245401 | C762_Hypothalamus | Hypothalamus | E4_young | E4/E4 | Wild-type | 3 months |
SA245402 | JJ3_73_Iso Cortex | Iso Cortex | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245403 | JJ3_76_Iso Cortex | Iso Cortex | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245404 | JJ3_66_Iso Cortex | Iso Cortex | E3_FAD | E3/E3 | Hemizygous | 12 months |
SA245405 | B427_Iso Cortex | Iso Cortex | E3_old | E3/E3 | Wild-type | 24 months |
SA245406 | B425_Iso Cortex | Iso Cortex | E3_old | E3/E3 | Wild-type | 24 months |
SA245407 | B354_Iso Cortex | Iso Cortex | E3_old | E3/E3 | Wild-type | 24 months |
SA245408 | B647_Iso Cortex | Iso Cortex | E3_young | E3/E3 | Wild-type | 3 months |
SA245409 | B652_Iso Cortex | Iso Cortex | E3_young | E3/E3 | Wild-type | 3 months |
SA245410 | B648_Iso Cortex | Iso Cortex | E3_young | E3/E3 | Wild-type | 3 months |
SA245411 | KK4_96_Iso Cortex | Iso Cortex | E4_FAD | E4/E4 | Hemizygous | 12 months |