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000271075 1001_ $$aAhmad, Shahzad$$b0
000271075 245__ $$aAssociation of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment
000271075 260__ $$aLondon$$bBioMed Central$$c2024
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000271075 520__ $$aIsoprostanes 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.Targeted 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.Increased 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.Oxidative 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.
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000271075 650_2 $$2MeSH$$aHumans
000271075 650_2 $$2MeSH$$aCognitive Dysfunction: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aOxidative Stress: physiology
000271075 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aFemale
000271075 650_2 $$2MeSH$$aMale
000271075 650_2 $$2MeSH$$aAged
000271075 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aPeptide Fragments: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aIsoprostanes: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aDisease Progression
000271075 650_2 $$2MeSH$$aMiddle Aged
000271075 650_2 $$2MeSH$$aInflammation: cerebrospinal fluid
000271075 650_2 $$2MeSH$$aMetabolomics: methods
000271075 650_2 $$2MeSH$$aAged, 80 and over
000271075 650_2 $$2MeSH$$aProstaglandins: cerebrospinal fluid
000271075 650_7 $$2Other$$aAPOE
000271075 650_7 $$2Other$$aAlzheimer’s disease
000271075 650_7 $$2Other$$aCerebrospinal fluid
000271075 650_7 $$2Other$$aIsoprostane
000271075 650_7 $$2Other$$aMild cognitive impairment
000271075 650_7 $$2Other$$aOxidative stress
000271075 650_7 $$2Other$$aProstaglandin
000271075 650_7 $$2NLM Chemicals$$aBiomarkers
000271075 650_7 $$2NLM Chemicals$$atau Proteins
000271075 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000271075 650_7 $$2NLM Chemicals$$aPeptide Fragments
000271075 650_7 $$2NLM Chemicals$$aIsoprostanes
000271075 650_7 $$2NLM Chemicals$$aamyloid beta-protein (1-42)
000271075 650_7 $$2NLM Chemicals$$aProstaglandins
000271075 7001_ $$aYang, Wei$$b1
000271075 7001_ $$aOrellana, Adelina$$b2
000271075 7001_ $$aFrölich, Lutz$$b3
000271075 7001_ $$ade Rojas, Itziar$$b4
000271075 7001_ $$aCano, Amanda$$b5
000271075 7001_ $$aBoada, Mercè$$b6
000271075 7001_ $$aHernández, Isabel$$b7
000271075 7001_ $$aHausner, Lucrezia$$b8
000271075 7001_ $$aHarms, Amy C.$$b9
000271075 7001_ $$aBakker, Margot H. M.$$b10
000271075 7001_ $$aCabrera-Socorro, Alfredo$$b11
000271075 7001_ $$aAmin, Najaf$$b12
000271075 7001_ $$0P:(DE-2719)2812825$$aRamírez, Alfredo$$b13$$udzne
000271075 7001_ $$aRuiz, Agustín$$b14
000271075 7001_ $$aVan Duijn, Cornelia M.$$b15
000271075 7001_ $$aHankemeier, Thomas$$b16
000271075 773__ $$0PERI:(DE-600)2506521-X$$a10.1186/s13195-024-01542-4$$gVol. 16, no. 1, p. 171$$n1$$p171$$tAlzheimer's research & therapy$$v16$$x1758-9193$$y2024
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