Abstract
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™ (10mg meso-zeaxanthin, 10mg lutein, 2mg zeaxanthin) or placebo (sunflower oil) for six months.The MRM-MS method determined serum POVPC sensitively (from 10µl 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.
Highlights
Alzheimer’s disease (AD), the most common form of dementia, is a degenerative brain disorder characterised by chronic and disabling memory impairment with cognitive impairment
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
We have extended our earlier investigations that showed an increase in the oxidative damage biomarkers isoprostanes and protein carbonyls in vascular dementia [22], [32] to determine whether (1) oxidised phospholipids (oxPLs) were increased in AD; (2) serum antioxidant potential was lower and; (3) there was any relationship between oxPL and disease activity
Summary
Alzheimer’s disease (AD), the most common form of dementia, is a degenerative brain disorder characterised by chronic and disabling memory impairment with cognitive impairment. Post-mortem investigations of affected brain regions have shown the accumulation of oxidative damage to protein, DNA and lipids in AD and oxidative stress has been considered as important in the pathogenesis of AD [3], [4]. Many lipid hydroperoxides, including oxidised phospholipids (oxPLs), are considered to be biologically relevant lipid signalling molecules [7], [8]. 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. POVPC and IsoP are considered as biomarkers of oxidative stress [13]–[15]
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