TY  - JOUR
AU  - Ahmad, Shahzad
AU  - Yang, Wei
AU  - Orellana, Adelina
AU  - Frölich, Lutz
AU  - de Rojas, Itziar
AU  - Cano, Amanda
AU  - Boada, Mercè
AU  - Hernández, Isabel
AU  - Hausner, Lucrezia
AU  - Harms, Amy C.
AU  - Bakker, Margot H. M.
AU  - Cabrera-Socorro, Alfredo
AU  - Amin, Najaf
AU  - Ramírez, Alfredo
AU  - Ruiz, Agustín
AU  - Van Duijn, Cornelia M.
AU  - Hankemeier, Thomas
TI  - Association of oxidative stress and inflammatory metabolites with Alzheimer’s disease cerebrospinal fluid biomarkers in mild cognitive impairment
JO  - Alzheimer's research & therapy
VL  - 16
IS  - 1
SN  - 1758-9193
CY  - London
PB  - BioMed Central
M1  - DZNE-2024-00947
SP  - 171
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Cognitive Dysfunction: cerebrospinal fluid
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Oxidative Stress: physiology
KW  - Biomarkers: cerebrospinal fluid
KW  - Female
KW  - Male
KW  - Aged
KW  - tau Proteins: cerebrospinal fluid
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Peptide Fragments: cerebrospinal fluid
KW  - Isoprostanes: cerebrospinal fluid
KW  - Disease Progression
KW  - Middle Aged
KW  - Inflammation: cerebrospinal fluid
KW  - Metabolomics: methods
KW  - Aged, 80 and over
KW  - Prostaglandins: cerebrospinal fluid
KW  - APOE (Other)
KW  - Alzheimer’s disease (Other)
KW  - Cerebrospinal fluid (Other)
KW  - Isoprostane (Other)
KW  - Mild cognitive impairment (Other)
KW  - Oxidative stress (Other)
KW  - Prostaglandin (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - Isoprostanes (NLM Chemicals)
KW  - amyloid beta-protein (1-42) (NLM Chemicals)
KW  - Prostaglandins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39080778
C2  - pmc:PMC11287840
DO  - DOI:10.1186/s13195-024-01542-4
UR  - https://pub.dzne.de/record/271075
ER  -