What can lipidomics tell us about the pathogenesis of Alzheimer disease?

Xiang, Yang; Lam, Sin Man; Shui, Guanghou

doi:10.1515/hsz-2015-0207

Cited by 25 publications

(21 citation statements)

References 88 publications

(106 reference statements)

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“…Lipidomics, a robust method for lipid analysis, has been defined as the characterisation of lipids in biological systems [10]. Oxidative lipidomic techniques offer sensitive and specific methods for high throughput analyses of oxPLs [11] such as 1-palmitoyl-2-(5′-oxo-valeroyl)- sn -glycero-3-phosphocholine (POVPC) and fatty acid oxidation, such as 8-iso-PGF2a (IsoP) [4]. POVPC is a truncated oxidation product of 1-palmitoyl-2-arachidonoyl- sn -phosphatidylcholine (PAPC); and IsoP belongs to the prostaglandin family that is formed by free radical peroxidation of arachidonic acid in membrane lipids.…”

Section: Introductionmentioning

confidence: 99%

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Ademowo

Dias

Milic

et al. 2017

Free Radical Biology and Medicine

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Alzheimer's disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age-matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8-isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay.AD patients (n=21) and healthy age-matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso-zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months.The MRM-MS method determined serum POVPC sensitively (from 10 µl serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age-matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003).In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function.

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Section: Introductionmentioning

confidence: 99%

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Ademowo

Dias

Milic

et al. 2017

Free Radical Biology and Medicine

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“…Of the lipid changes reported in the CSF, plasma, and serum of patients with AD, many do not necessarily correlate with those described previously in the CNS [6]. For instance, free cholesterol and ChoE were reported to be downregulated in the CSF although they are increased in the brain of patients with AD [86] (see Section 3.1.).…”

Section: Specific Lipid Alterations As Potential Biomarkers In Admentioning

confidence: 91%

“…On the one hand, therapeutic approaches focused on combating amyloid pathology have generally failed to prevent AD progression in clinical trials (see Section 4, [17,18]), while on the other hand, transgenic AD animal models, mostly created by incorporating human mutated APP and/or PS1 into the animal genome, do not recapitulate all the neuropathological features of AD, and not even the large scale neuronal death that occurs during this pathology [19]. Moreover, the alterations to membrane lipids in neurons of patients with AD suggest that the changes to lipid bilayer could be the first event in the amyloid cascade and related pathways [6]. Indeed, the normalization of membrane lipids is associated with cognitive restoration (see Section 5.2).…”

Section: Historical Perspective On the Pathophysiology Of Alzheimer'smentioning

confidence: 99%

“…Since mutations in both APP and presenilins are the major causal factors in FAD etiology, altered APP metabolism was assumed to be the principal cause triggering AD, leading to the formulation of the amyloid cascade hypothesis more than 20 years ago. Finally, it is notable that all these participants in APP metabolism, APP and secretases, are membrane-associated proteins influenced by the composition and structure of cell membrane lipids that in turn modulate APP metabolism [6]. Figure 1.…”

Section: Introductionmentioning

confidence: 99%

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Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

Torres¹,

Busquets²,

Escribá³

2016

Update on Dementia

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Alzheimer's disease (AD) is a neurodegenerative disorder that causes severe and progressive cognitive impairment. The discovery of specific mutations related to AD supported the amyloid cascade hypothesis, which postulates that the accumulation of the amyloid-β (Aβ) peptide triggers neuronal death and dementia. However, most drugs that aim to prevent Aβ accumulation or tau phosphorylation have consistently failed in clinical trials. This would suggest that the amyloid pathology lies downstream of (an)other cellular event(s) that is/are responsible for AD pathogenesis. In this context, several lipid alterations have been described in the brain and in peripheral fluids of patients with AD, suggesting the involvement of lipids in the etiology of this condition. Indeed, the central nervous system (CNS) has the highest lipid content in the body, next to adipose tissue, and it is thought that normalization of brain membrane lipid levels would revert AD-related pathogenic events. In this sense, novel hydroxylated derivatives of docosahexaenoic acid (DHA) such as natural resolvins or synthetic hydroxy-DHA (HDHA, DHALifort) can modulate membrane lipid composition and show remarkable beneficial effects on AD hallmarks, such as prevention of amyloid production and tau phosphorylation, and cognitive restoration in animal models. Therefore, normalization of the neuronal lipid environment by hydroxyl-DHA and/or other lipids may constitute a promising therapy for AD treatment, memory loss and, possibly, other types of dementia.

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“…A comprehensive list of vast lipids classes and subclasses combined with their common abbreviations can be found in the classification system provided by Lipid MAPS consortium [8]. Lipidomics studies can provide critical insights toward the development of an improved understanding of lipids metabolism and for the identification of new biomarkers or therapeutic targets of related diseases mentioned above [3,[9][10][11][12][13]. In the past 5 years, a variety of reviews have been published on the applications of lipidomics in different aspects, such as infection and inflammation [14], biology and medicine [10,15,16], clinical lipidomics [17,18], and lipid peroxidation-related diseases [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Recent progresses of derivatization approaches in the targeted lipidomics analysis by mass spectrometry

Zhao

Zhu

Liu

2020

J of Separation Science

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Lipidomics plays an essential role in the development of an improved understanding of lipids metabolism and the identification of new biomarkers or therapeutic targets of related diseases. The strong analytical power of mass spectrometry and its rapid developments in the respect of instruments and techniques have significantly accelerated the emerging lipidomics and related application fields in biology, medicine, and pharmacy. The strategy of chemical derivatization can remarkably improve the shortcomings of mass spectrometric analytical technologies of shotgun lipidomics and liquid chromatography mass spectrometry, and in the past decade many related studies have been reported for fatty acids, glycerophospholipids, sphingomyelins, monoglycerides, diacylglycerols, long-chain bases, steroids, and so on. Therefore, this review will focus on new chemical derivatization approaches about the research progresses of shotgunbased and liquid chromatography mass spectrometry-based targeted lipidomics (from 2005 to July 2019, most of reports emerged in the past 5 years), and put forward the problems and prospects in this field. It is expected to be helpful for the design and synthesis of new derivatization reagents, especially the outstanding stable isotope labeling derivatization reagents, and the development and application of new chemical derivatization strategies and matched mass spectrometric analysis methods. K E Y W O R D Schemical derivatization, lipidomics, liquid chromatography mass spectrometry, shotgun lipidomics, stable isotope labeling 1838

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What can lipidomics tell us about the pathogenesis of Alzheimer disease?

Cited by 25 publications

References 88 publications

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Brain Lipids in the Pathophysiology and Treatment of Alzheimer’s Disease

Recent progresses of derivatization approaches in the targeted lipidomics analysis by mass spectrometry

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