Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Preparation and Lipid Extraction
2.2. Lipid Analysis
2.2.1. Analysis of Cholesterol and Derivatives by GC-MS/MS
2.2.2. Phospholipids Analysis by Electrospray Mass Spectrometry (ESI-MS)
2.2.3. Analysis of FA Composition by GC
2.3. Cultures of Primary Neurons
2.4. Aβ 38, 40 and 42 Measurements
2.5. Western Blotting
2.6. Data Processing
3. Results
3.1. APOE Genotype Disturbs Cholesterol Turnover
3.2. Levels of PC and PE and Changes in Their Composition in APOE4-KI Mice
3.3. APOE Genotype and Fatty Acid Profile and Metabolism
3.4. Lipid Dysregulations and Gene Expression in APOE Genotypes
3.5. Neurons of APOE4-KI Mice Produce a Higher Amount of Aβ Peptide
4. Discussion
4.1. Altered Cholesterol Turnover in APOE4-KI Mice
4.2. APOE4 Genotype Is Associated to Lower Levels of Phosphatidylethanolamines Bearing Polyunsaturated Fatty Acids
4.3. Elevated Levels of MUFAs, Particularly Omega-9 FA, in APOE4-KI Mice
4.4. Interrelationship between Lipid Dys-Homeostasis and AD Pathological Markers
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Lazar, A.-N.; Hanbouch, L.; Boussicaut, L.; Fourmaux, B.; Daira, P.; Millan, M.J.; Bernoud-Hubac, N.; Potier, M.-C. Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology. Cells 2022, 11, 3616. https://doi.org/10.3390/cells11223616
Lazar A-N, Hanbouch L, Boussicaut L, Fourmaux B, Daira P, Millan MJ, Bernoud-Hubac N, Potier M-C. Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology. Cells. 2022; 11(22):3616. https://doi.org/10.3390/cells11223616
Chicago/Turabian StyleLazar, Adina-Nicoleta, Linda Hanbouch, Lydie Boussicaut, Baptiste Fourmaux, Patricia Daira, Mark J. Millan, Nathalie Bernoud-Hubac, and Marie-Claude Potier. 2022. "Lipid Dys-Homeostasis Contributes to APOE4-Associated AD Pathology" Cells 11, no. 22: 3616. https://doi.org/10.3390/cells11223616