Abstract
Lipids, as the basic component of cell membranes, play an important role in human health as well as brain function. The brain is highly enriched in lipids, and disruption of lipid homeostasis is related to neurologic disorders as well as neurodegenerative diseases such as Alzheimer’s disease (AD). Aging is associated with changes in lipid composition. Alterations of fatty acids at the level of lipid rafts and cerebral lipid peroxidation were found in the early stage of AD. Genetic and environmental factors such as apolipoprotein and lipid transporter carrying status and dietary lipid content are associated with AD. Insight into the connection between lipids and AD is crucial to unraveling the metabolic aspects of this puzzling disease. Recent advances in lipid analytical methodology have led us to gain an in-depth understanding on lipids. As a result, lipidomics have becoming a hot topic of investigation in AD, in order to find biomarkers for disease prediction, diagnosis, and prevention, with the ultimate goal of discovering novel therapeutics.
Highlights
There were ~46.8 million dementia cases worldwide in 2015 according to the world Alzheimer report, with an estimated 9.9 million new cases per year [1], indicating the global burden of dementia
APP/presenilin 1 (PS1) Alzheimer’s disease (AD) mice fed deuterium-reinforced PUFAs (D-PUFAs) showed lower lipid peroxidation products and Aβ40/Aβ38 production in the hippocampus compared to those fed hydrogenated PUFAs (H-PUFAs), there was no change in learning and memory deficits [52]
Using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 17 lipid peroxidation biomarkers in urine samples, 17(RS)-10-epi-SC-∆15-11-dihomo-IsoF, PGE2, NeuroP, IsoP and IsoF showed differences between patients with mild AD and control, which seems promising as potential early AD biomarkers due to their easy accessibility compared to CSF [107]
Summary
There were ~46.8 million dementia cases worldwide in 2015 according to the world Alzheimer report, with an estimated 9.9 million new cases per year [1], indicating the global burden of dementia. Cerebral lipids account for at least 50% of dry brain weight—the most lipid-rich organ next to the adipose tissue [2]. Brain lipids are comprised of 50% phospholipids, below 40% glycolipids, 10% cholesterol, cholesterol ester and traces of triglycerides. Long-chain polyunsaturated fatty acids (LC-PUFAs) account for 25–30% of the total fatty acids (FAs) in the human brain, including docosahexaenoic acid (DHA) and arachidonic acid (AA) [2]. Cerebral lipid peroxidation was found to be an early event in AD. Brains of AD patients display a higher number of lipoid granules (or adipose inclusions) in glia, suggesting aberrant lipid metabolism. Example arachidonic acid (AA), docosahexaenoic acid (DHA) monoacylglycerol (MAG), diacylglycerol (DAG), triacylglycerol ( triglyceride, TG) phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS) sphingomyelin, ceramide, sulfatide, ganglioside cholesterol, vitamin D carotenoid, vitamin E & K lipid A lovastatin
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