Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

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™ (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.

Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention

“…The excessive intake of vitamin A in the body causes poisoning, and b-carotene is a safe source of vitamin A because it can be converted to vitamin A after entering the body when needed. Studies have shown that b-carotene significantly improves behavioral abilities, learning, memory, and cognitive function in mice and rats through its antioxidant effect by scavenging free radicals (3,457).…”

Partial Mitigation of Oxidized Phospholipid-Mediated Mitochondrial Dysfunction in Neuronal Cells by Oxocarotenoids

“…Our own work has shown that lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD patients with vascular co-morbidities compared to healthy subjects [18]. In another study we have shown that the serum phospholipid oxidation product POVPC was higher in AD compared with age-matched control subjects but was not reduced by carotenoid supplementation in extant disease [19]. Taken together these studies indicate an inverse relationship between carotenoid concentration and the oxidised phospholipid POVPC in AD.…”

Stress causes cognitive impairment by affecting cholesterol efflux and reuptake leading to abnormalities in lipid metabolism of rats

“…Glycerophospholipids, which are the most common phospholipids in vivo, comprise PC, PE, phosphatidylserine (PS), phosphatidylglycerol (PG), and phosphatidylinositol (PI). It was known that patients with AD have higher serum levels of PC, indicating that elevated PC may contribute to cognitive impairment (Ademowo et al, 2017), and higher brain levels of PC may lead to the impairment of the brain synapses. The elevated PC causes a decrease in acetylcholine release, which affects synaptic plasticity (Ulus et al, 1989;Wurtman, 2015).…”