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@ARTICLE{Ahmad:271075,
      author       = {Ahmad, Shahzad and Yang, Wei and Orellana, Adelina and
                      Frölich, Lutz and de Rojas, Itziar and Cano, Amanda and
                      Boada, Mercè and Hernández, Isabel and Hausner, Lucrezia
                      and Harms, Amy C. and Bakker, Margot H. M. and
                      Cabrera-Socorro, Alfredo and Amin, Najaf and Ramírez,
                      Alfredo and Ruiz, Agustín and Van Duijn, Cornelia M. and
                      Hankemeier, Thomas},
      title        = {{A}ssociation of oxidative stress and inflammatory
                      metabolites with {A}lzheimer’s disease cerebrospinal fluid
                      biomarkers in mild cognitive impairment},
      journal      = {Alzheimer's research $\&$ therapy},
      volume       = {16},
      number       = {1},
      issn         = {1758-9193},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2024-00947},
      pages        = {171},
      year         = {2024},
      abstract     = {Isoprostanes 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.},
      keywords     = {Humans / Cognitive Dysfunction: cerebrospinal fluid /
                      Alzheimer Disease: cerebrospinal fluid / Oxidative Stress:
                      physiology / Biomarkers: cerebrospinal fluid / Female / Male
                      / Aged / tau Proteins: cerebrospinal fluid / Amyloid
                      beta-Peptides: cerebrospinal fluid / Peptide Fragments:
                      cerebrospinal fluid / Isoprostanes: cerebrospinal fluid /
                      Disease Progression / Middle Aged / Inflammation:
                      cerebrospinal fluid / Metabolomics: methods / Aged, 80 and
                      over / Prostaglandins: cerebrospinal fluid / APOE (Other) /
                      Alzheimer’s disease (Other) / Cerebrospinal fluid (Other)
                      / Isoprostane (Other) / Mild cognitive impairment (Other) /
                      Oxidative stress (Other) / Prostaglandin (Other) /
                      Biomarkers (NLM Chemicals) / tau Proteins (NLM Chemicals) /
                      Amyloid beta-Peptides (NLM Chemicals) / Peptide Fragments
                      (NLM Chemicals) / Isoprostanes (NLM Chemicals) / amyloid
                      beta-protein (1-42) (NLM Chemicals) / Prostaglandins (NLM
                      Chemicals)},
      cin          = {Patient Studies Bonn ; Patient Studies (Bonn)},
      ddc          = {610},
      cid          = {I:(DE-2719)1011101},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39080778},
      pmc          = {pmc:PMC11287840},
      doi          = {10.1186/s13195-024-01542-4},
      url          = {https://pub.dzne.de/record/271075},
}