Journal article
Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease
- Abstract:
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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, Aβ-42, p-tau, and total tau levels overall and stratified by APOE genotype 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, Aβ-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aβ-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 Aβ-42 levels was found only in APOE ε4 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 1.7MB, Terms of use)
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- Publisher copy:
- 10.1186/s13195-020-00680-9
Authors
- Publisher:
- BioMed Central
- Journal:
- Alzheimer's research & therapy More from this journal
- Volume:
- 12
- Issue:
- 1
- Article number:
- 124
- Publication date:
- 2020-10-02
- Acceptance date:
- 2020-09-09
- DOI:
- EISSN:
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1758-9193
- Pmid:
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33008436
- Language:
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English
- Keywords:
- Pubs id:
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1137413
- Local pid:
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pubs:1137413
- Deposit date:
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2020-12-02
Terms of use
- Copyright holder:
- Ahmad et al.
- Copyright date:
- 2020
- Rights statement:
- ©2020 The Authors.
- Notes:
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Licence:
- CC Attribution (CC BY)
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