Phospholipid oxidation and carotenoid supplementation in Alzheimer's disease patients.
Phospholipid oxidation and carotenoid supplementation in Alzheimer's disease patients.
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DOI：
10.1016/j.freeradbiomed.2017.03.008
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发表时间：
2017-07
影响因子：
7.4
通讯作者：
Griffiths HR
中科院分区：
文献类型：
--
作者：
Ademowo OS;Dias HKI;Milic I;Devitt A;Moran R;Mulcahy R;Howard AN;Nolan JM;Griffiths HR
阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，其特征是记忆力、认知功能下降和行为改变。 AD 中脂质过氧化的一般标志物增加，并且活性氧被认为与认知能力下降的病因有关。 AD 血清中的类胡萝卜素已耗尽，因此我们比较了 AD 和年龄匹配的对照受试者在补充类胡萝卜素之前和之后的血清脂质氧化情况。使用电喷雾电离串联质谱 (MS) 和多反应监测 (MRM) 分析新型氧化磷脂生物标志物 1-棕榈酰-2-(5'-氧代-戊酰)-sn-甘油-3-磷酸胆碱 (POVPC)，通过 ELISA 测量 8-异前列腺素 (IsoP)，通过比色测定测量铁还原抗氧化电位 (FRAP)。 AD 患者 (n=21) 和健康年龄匹配的对照受试者 (n=16) 补充 Macushield™（10 毫克内消旋玉米黄质、10 毫克叶黄素、2 毫克玉米黄质）或安慰剂（葵花籽油）六个月。 MRM-MS 方法可灵敏（来自 10 µl 血清）且可重复地测定血清 POVPC（CV=7.9%）。在基线时，与年龄匹配的对照组相比，AD 受试者的血清 POVPC 较高（p=0.017），并且认知功能与 POVPC 呈负相关（r=-0.37；p=0.04）。经过六个月的类胡萝卜素干预后，AD 患者的血清 POVPC 与健康对照者没有差异。然而，在类胡萝卜素干预六个月后，对照组受试者的 POVPC 显着高于基线 (p=0.03)。血清 IsoP 浓度与疾病或补充剂无关。 AD 患者的血清 FRAP 显着低于健康对照，但类胡萝卜素干预后血清 FRAP 没有变化 (p=0.003)。总之，与对照受试者相比，AD 患者的血清 POVPC 较高，并且不会因补充类胡萝卜素而降低，并且与认知功能相关。可以使用稳健且灵敏的 MS-MRM 方法测定血清中的 POVPC。与年龄匹配的对照相比，AD 患者血清中的 POVPC 较高。 POVPC 与简易精神状态检查呈负相关。补充类胡萝卜素后，对照血清中的 POVPC 增加。
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. POVPC can be determined in serum using a robust and sensitive MS-MRM method. POVPC is higher in AD patient serum compared to age-matched controls. POVPC correlates inversely with mini-mental state examination. POVPC is increased in control sera after carotenoid supplementation.