% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@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},
}