Ahmad, Shahzad ORCID: 0000-0002-8658-3790, Orellana, Adelina, Kohler, Isabelle ORCID: 0000-0002-3629-1597, Froelich, Lutz, de Rojas, Itziar, Gil, Silvia, Boada, Merce, Hernandez, Isabel, Hausner, Lucrezia, Bakker, Margot H. M., Cabrera-Socorro, Alfredo, Amin, Najaf, Ramirez, Alfredo ORCID: 0000-0003-4991-763X, Ruiz, Agustin, Hankemeier, Thomas and Van Duijn, Cornelia M. (2020). Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease. Alzheimers Res. Ther., 12 (1). LONDON: BMC. ISSN 1758-9193

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Abstract

Background Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer's disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD. Methods The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, A beta-42,p-tau, and total tau levels overall and stratified byAPOEgenotype and with MCI to AD progression. Results Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, A beta-42,p-tau, and total tau, while LPA C14:0 and C20:1 associated only with A beta-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with A beta-42 levels was found only in APOE epsilon 4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort. Conclusions Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ahmad, ShahzadUNSPECIFIEDorcid.org/0000-0002-8658-3790UNSPECIFIED
Orellana, AdelinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kohler, IsabelleUNSPECIFIEDorcid.org/0000-0002-3629-1597UNSPECIFIED
Froelich, LutzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Rojas, ItziarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gil, SilviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boada, MerceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez, IsabelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hausner, LucreziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bakker, Margot H. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabrera-Socorro, AlfredoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amin, NajafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramirez, AlfredoUNSPECIFIEDorcid.org/0000-0003-4991-763XUNSPECIFIED
Ruiz, AgustinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hankemeier, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Duijn, Cornelia M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-315846
DOI: 10.1186/s13195-020-00680-9
Journal or Publication Title: Alzheimers Res. Ther.
Volume: 12
Number: 1
Date: 2020
Publisher: BMC
Place of Publication: LONDON
ISSN: 1758-9193
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MILD COGNITIVE IMPAIRMENT; TRAUMATIC BRAIN-INJURY; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; VASCULAR DEMENTIA; MOLECULAR-CLONING; LIPID MEDIATORS; LPA RECEPTORS; TAU; BETA-AMYLOID(1-42)Multiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31584

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