Evidence map›Paper›PMID 39080778›Full record

ArticleAlzheimer's research & therapy2024

Association of oxidative stress and inflammatory metabolites with Alzheimer's disease cerebrospinal fluid biomarkers in mild cognitive impairment.

Shahzad Ahmad, Wei Yang, Adelina Orellana, Lutz Frölich, Itziar de Rojas, Amanda Cano, Mercè Boada, Isabel Hernández, Lucrezia Hausner, Amy C Harms and 7 more

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  15. A seven-year longitudinal study of the Alzheimer's disease blood metabolome.medRxiv : the preprint server for health sciences · 2025
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  20. Open veterinary journal · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Shahzad Ahmad *Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Wei Yang *Metabolomics and Analytics Center, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Adelina OrellanaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Lutz FrölichDepartment of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany.
Itziar de RojasAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Amanda CanoAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Mercè BoadaAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Isabel HernándezAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Lucrezia HausnerDepartment of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159, Mannheim, Germany.
Amy C HarmsMetabolomics and Analytics Center, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Margot H M BakkerDiscovery Research, AbbVie Deutschland GmbH & Co. KG, 67061, KnollstrasseLudwigshafen, Germany.
Alfredo Cabrera-SocorroJanssen Pharmaceutical NV, Turnhoutseweg 30, 2340, Beerse, Belgium.
Najaf AminDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Alfredo RamírezDepartment for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
Agustín RuizAce Alzheimer Center Barcelona - Universitat Internacional de Catalunya, Barcelona, Spain.
Cornelia M Van DuijnDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. cornelia.vanduijn@ndph.ox.ac.uk.
Thomas HankemeierDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. hankemeier@lacdr.leidenuniv.nl.

Funding

EuroNanoMed III AC17/00100Innovative Medicines Initiative 115975Nederlandse Organisatie voor Wetenschappelijk Onderzoek 184.034.019
6 · The paper itself

Abstract

backgroundIsoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects.

methodsTargeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LCMS) in 147 paired plasma-CSF samples from the Ace Alzheimer Center Barcelona and 58 CSF samples of MCI patients from the Mannheim/Heidelberg cohort. Linear regression was used to evaluate the association of metabolites with CSF levels of ATN biomarkers in the overall sample and stratified by Aβ-42 pathology and APOE genotype. We further evaluated the role of metabolites in MCI to AD dementia progression.

resultsIncreased CSF levels of PGF2α, 8,12-iso-iPF2α VI, and 5-iPF2α VI were significantly associated (False discovery rate (FDR) < 0.05) with higher p-tau levels. Additionally, 8,12-iso-iPF2α VI was associated with increased total tau levels in CSF. In MCI due to AD, PGF2α was associated with both p-tau and total tau, whereases 8,12-iso-iPF2α VI was specifically associated with p-tau levels. In APOE stratified analysis, association of PGF2α with p-tau and t-tau was observed in only APOE ε4 carriers while 5-iPF2α VI showed association with both p-tau and t-tau in APOE ε33 carriers. CSF levels of 8,12- iso-iPF2α VI showed association with p-tau and t-tau in APOE ε33/APOE ε4 carriers and with t-tau in APOE ε3 carriers. None of the metabolites showed evidence of association with MCI to AD progression.

conclusionsOxidative stress (8,12-iso-iPF2α VI) and inflammatory (PGF2α) biomarkers are correlated with biomarkers of AD pathology during the prodromal stage of AD and relation of PGF2α with tau pathology markers may be influenced by APOE genotype.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionOxidative Stresstau ProteinsAgedAged, 80 and overDisease ProgressionFemaleHumansInflammationIsoprostanesMaleMetabolomicsMiddle AgedAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersIsoprostanesPeptide FragmentsProstaglandinstau ProteinsAlzheimer’s diseaseAPOECerebrospinal fluidIsoprostaneMild cognitive impairmentOxidative stressProstaglandin

Identifiers

PMID39080778
PMCPMC11287840

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.