Abstract
Alzheimer’s disease (AD) is a progressive and incurable brain disorder that has been associated with structural changes in brain phospholipids (PLs), including diacyl species and ether-linked PLs known as plasmalogens. Most studies have characterized total changes in brain PL pools (e.g., choline plasmalogens), particularly in prefrontal cortex, but detailed and quantitative information on the molecular PL species impacted by the disease is limited. In this study, we used a comprehensive mass-spectrometry method to quantify diacyl and plasmalogen species, alkyl synthetic precursors of plasmalogens, and lysophospholipid degradation products of diacyl and plasmalogen PLs, in postmortem samples of prefrontal cortex from 21 AD patients and 20 age-matched controls. Total PLs were also quantified with gas-chromatography analysis of bound fatty acids following thin layer chromatography isolation. There was a significant 27% reduction in the concentration (nmol/g wet weight) of choline plasmalogen containing stearic acid (alkenyl group) and docosahexaenoic acid in AD compared to controls. Stearic acid concentration in total PLs was reduced by 26%. Our findings suggest specific changes in PLs containing stearic acid and docosahexaenoic acid in AD prefrontal cortex, highlighting structural and turnover PL pathways that could be targeted.
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Abbreviations
- AD:
-
Alzheimer’s disease
- BHT:
-
Butylated hydroxytoluene
- CV:
-
Coefficient of variation
- DHA:
-
Docosahexaenoic acid
- DHAP:
-
Dihydroxyacetonephosphate
- EDTA:
-
Ethylenediaminetetraacetic acid
- GC:
-
Gas-chromatography
- HPLC:
-
High-performance liquid chromatography
- Lyso PakCho:
-
1-alkyl-2-hydroxy phosphatidylcholine
- Lyso PtdCho:
-
Lyso phsphatidylcholine
- Lyso PakEtn:
-
1-alkyl-2-hydroxy phosphatidylethanolamine
- Lyso PtdEtn:
-
Lyso phosphatidylethanolamine
- Lyso PlsCho:
-
Lyso plasmenylcholine
- Lyso PlsEtn:
-
Lyso plasmenylethanolamine
- PakCho:
-
Alkyl-acyl phosphatidylcholine
- PakEtn:
-
Alkyl-acyl phosphatidylethanolamine
- PtdCho:
-
Diacyl phosphatidylcholine
- PtdEtn:
-
Diacyl phosphatidylethanolamine
- PLs:
-
Phospholipids
- PlsCho:
-
Choline plasmalogens
- PlsEtn:
-
Ethanolamine plasmalogens
- PMI:
-
Postmortem interval
- PUFAs:
-
Polyunsaturated fatty acids
- Sn:
-
Stereospecifically numbered
- TLC:
-
Thin layer chromatography
- UPLC-MS/MS:
-
Ultra-high-performance liquid chromatography tandem mass-spectrometry
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Acknowledgements
The authors would like to thank the families and participants of the UCD ADRC for their generous donations. Research reported in this publication was supported by the National Institute On Aging of the National Institutes of Health under Award Number P30AG010129, Alzheimer’s Association (2018-AARGD-591676) and by the Project of the NARO Bio-oriented Technology Research Advancement Institution (R&D matching funds on the field for Knowledge Integration and innovation) under Award number 1074345. Y.O. is a recipient of a fellowship from the Japan Society for the Promotion of Science Core-to-Core Program, A (Advanced Research Networks entitled “Establishment of international agricultural immunology research-core for a quantum improvement in food safety”). The authors would like to thank Dr. Shinichi Sakasegawa and Mr. Kenji Konishi in Asahi Kasei Pharma Corporation for providing phospholipase A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding agencies involved.
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Study design—all authors, Experimental work—Y.O., S.K., Data analysis— Y.O., A.T., D.H., B.D L.J, Writing manuscript—Y.O., A.T., Funding acquisition, A.T. and K.N.
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The study was approved by the Institutional Review Board of the University of California Davis, and written consent was obtained for each participant for autopsy evaluations (Protocol # 215830).
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Otoki, Y., Kato, S., Nakagawa, K. et al. Lipidomic Analysis of Postmortem Prefrontal Cortex Phospholipids Reveals Changes in Choline Plasmalogen Containing Docosahexaenoic Acid and Stearic Acid Between Cases With and Without Alzheimer’s Disease. Neuromol Med 23, 161–175 (2021). https://doi.org/10.1007/s12017-020-08636-w
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DOI: https://doi.org/10.1007/s12017-020-08636-w