Englander Institute for Precision Medicine

Metabolomics profiling reveals distinct, sex-specific signatures in the serum and brain metabolomes in the mouse models of Alzheimer's disease.

TitleMetabolomics profiling reveals distinct, sex-specific signatures in the serum and brain metabolomes in the mouse models of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2023
AuthorsPandey RS, Arnold M, Batra R, Krumsiek J, Kotredes KP, Garceau D, Williams H, Sasner M, Howell GR, Kaddurah-Daouk R, Carter GW
JournalbioRxiv
Date Published2023 Dec 22
Abstract

INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species provides a promising entry point for translation. METHODS: We investigated differences of serum and brain metabolites between the early-onset 5XFAD and late-onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls at six months of age.

RESULTS: We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more pronounced differences in serum.

DISCUSSION: Several of our findings were consistent with results in humans, showing glycerophospholipids reduction in serum of APOE4 carriers and replicating the serum metabolic imprint of the APOE4 genotype. Our work thus represents a significant step towards translating metabolic dysregulation from model organisms to human AD.

DOI10.1101/2023.12.22.573059
Alternate JournalbioRxiv
PubMed ID38187571
PubMed Central IDPMC10769366
Grant ListU54 AG054345 / AG / NIA NIH HHS / United States
U19 AG063744 / AG / NIA NIH HHS / United States
RC2 AG036547 / AG / NIA NIH HHS / United States
U01 AG061359 / AG / NIA NIH HHS / United States
R01 AG048015 / AG / NIA NIH HHS / United States
R01 AG046171 / AG / NIA NIH HHS / United States
U01 AG046152 / AG / NIA NIH HHS / United States
U01 AG061356 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
R01 AG069901 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
RF1 AG059093 / AG / NIA NIH HHS / United States
RF1 AG057473 / AG / NIA NIH HHS / United States
RF1 AG057452 / AG / NIA NIH HHS / United States
U01 AG046161 / AG / NIA NIH HHS / United States
RF1 AG058942 / AG / NIA NIH HHS / United States
RF1 AG051550 / AG / NIA NIH HHS / United States
R01 AG036836 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States

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