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Omega6/omega3 ethanolamin‐containing plasmalogen (PlsEtn) ratio as a biomarker of Alzheimer's disease progression
Author(s) -
Lorenzi Marco,
Fleuriot Lucile,
Debayle Delphine,
Barelli Helene
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.046040
Subject(s) - docosahexaenoic acid , polyunsaturated fatty acid , arachidonic acid , eicosapentaenoic acid , chemistry , myelin , medicine , fatty acid , endocrinology , biochemistry , central nervous system , enzyme
Abstract Background Single‐cell transcriptomic analysis of AD has revealed that myelination‐related processes are perturbed in brain, suggesting a key role in AD pathophysiology. Oligodendrocytes support neurons and signal transmission in the central nervous system by wrapping axons with myelin, a lipid‐rich membrane structure that depend on fatty acid synthesis and metabolism. Beside galactolipids, the major lipids of myelin are cholesterol and ethanolamin‐containing plasmalogens (PlsEtn). Polyunsaturated fatty acids (PUFA) such as docosahexaenoic acid (DHA, 22:6, omega3), eicosapentaenoic acid (EPA, 20:5, omega3), arachidonic acid (20:4, omega6), and monounsaturated fatty acid oleic acid (18:1, omega9) are the major constituent FA at the sn‐2 position of Pls. Among them, DHA is the most efficient to confer very specific physicochemical properties and membrane fluidity (Pinot et al., 2014). Method Our results in lipidomics reveal that brain PUFAs‐Pls levels decrease importantly in cortex T1 and particularly in the frontal white matter (FWM) of AD individuals. Result We hypothesized that blood and brain phospholipids deficits could be closely associated with disease progression in AD. This hypothesis is corroborated by our previous results showing statistical association between PUFA‐phospholipids (PC, PE, PS) blood concentrations and brain atrophy and cognition in the ADNI cohort (previous communication at AAIC 2018). In follow‐up analyses, we further demonstrated that blood PUFAs‐PlsEtn deficits specifically related to demyelination present the most significative statistical association between an increase of the ratio omega6/omega3 and the increase of AD severity (high disease stage). Conclusion Blood omega6/omega3 PUFAs‐PlsEtn ratio could be a biomarker of the demyelination process observed in AD progression.