Phospholipid oxidation and carotenoid supplementation in Alzheimer's disease patients.
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.
Life & Health Sciences, Aston University, Birmingham, UK.
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Ademowo
Life & Health Sciences, Aston University, Birmingham, UK.
H K I
HKI
Dias
Life & Health Sciences, Aston University, Birmingham, UK.
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Milic
Life & Health Sciences, Aston University, Birmingham, UK.
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A
Devitt
Nutrition Research Centre Ireland, Health Science, Waterford Institute of Technology, Cork Road, Waterford, Ireland.
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Moran
Waterford University Hospital, Age-related Care Unit, Waterford, Ireland.
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Mulcahy
Howard Foundation, Cambridge, UK; Downing College, University of Cambridge, Cambridge, UK.
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Howard
Nutrition Research Centre Ireland, Health Science, Waterford Institute of Technology, Cork Road, Waterford, Ireland.
J M
JM
Nolan
Life & Health Sciences, Aston University, Birmingham, UK; Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. Electronic address: h.r.griffiths@surrey.ac.uk.
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Griffiths
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000628:therapy; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002338:Carotenoids / Q000737:chemistry / Q000627:therapeutic use; D003072:Cognition Disorders / Q000378:metabolism* / Q000628:therapy; D003131:Combined Modality Therapy; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D014975:Lutein / Q000627:therapeutic use; D008297:Male; D010084:Oxidation-Reduction; D010742:Phospholipid Ethers / Q000097:blood*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D065146:Zeaxanthins / Q000627:therapeutic use
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; D000975:Antioxidants; D015415:Biomarkers; D010742:Phospholipid Ethers; D010743:Phospholipids; D017382:Reactive Oxygen Species; D065146:Zeaxanthins; D002338:Carotenoids; C584722:meso-zeaxanthin; D014975:Lutein
Cognitive function; Lipid peroxidation; Lutein; Mass spectrometry; Meso-zeaxanthin; Oxidative stress; POVPC; Supplementation; Zeaxanthin