Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review.
Association of Docosahexaenoic Acid Supplementation With Alzheimer Disease Stage in Apolipoprotein E ε4 Carriers: A Review.
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DOI：
10.1001/jamaneurol.2016.4899
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发表时间：
2017-03-01
期刊：
影响因子：
29
通讯作者：
Chui HC
中科院分区：
文献类型：
--
作者：
Yassine HN;Braskie MN;Mack WJ;Castor KJ;Fonteh AN;Schneider LS;Harrington MG;Chui HC
载脂蛋白E ε4（APOE 4）等位基因鉴定了一个独特的人群，该人群具有患阿尔茨海默病（AD）的显著风险。二十二碳六烯酸（DHA）是一种必需的ω-3脂肪酸，对神经元突触和膜流动性的形成至关重要。观察性研究表明，ω-3摄入量（包括DHA）与AD发病风险降低有关。相比之下，ω-3脂肪酸的随机临床试验产生了混合和不一致的结果。DHA、APOE基因型和AD病理变化阶段之间的相互作用可以解释文献中报道的DHA补充剂的混合结果。虽然ω-3在症状性AD中的随机临床试验结果是负面的，但在AD痴呆前期阶段的几项ω-3观察和临床试验表明，补充ω-3可能减缓APOE 4携带者的早期记忆衰退。APOE 4等位基因改变DHA向大脑传递的几种机制可能适用于AD痴呆前期阶段的DHA补充剂。加速DHA催化作用的证据（例如，磷脂酶和氧化途径的活化）可以解释补充ω-3对AD痴呆缺乏疗效。在痴呆前期而非AD痴呆患者中，DHA补充与认知益处的相关性表明，早期补充ω-3可降低APOE 4携带者AD症状的风险或延迟其发作。脑成像的最新进展可能有助于确定未来DHA临床试验的最佳时机。在AD痴呆发作前对APOE 4携带者补充大剂量DHA可能是降低AD发病率的一种有希望的方法。考虑到DHA补充剂的安全性、可用性和可负担性，有必要对APOE 4携带者进行ω-3干预。
The apolipoprotein E ε4 (APOE4) allele identifies a unique population that is at significant risk for developing Alzheimer disease (AD). Docosahexaenoic acid (DHA) is an essential ω-3 fatty acid that is critical to the formation of neuronal synapses and membrane fluidity. Observational studies have associated ω-3 intake, including DHA, with a reduced risk for incident AD. In contrast, randomized clinical trials of ω-3 fatty acids have yielded mixed and inconsistent results. Interactions among DHA, APOE genotype, and stage of AD pathologic changes may explain the mixed results of DHA supplementation reported in the literature. Although randomized clinical trials of ω-3 in symptomatic AD have had negative findings, several observational and clinical trials of ω-3 in the predementia stage of AD suggest that ω-3 supplementation may slow early memory decline in APOE4 carriers. Several mechanisms by which the APOE4 allele could alter the delivery of DHA to the brain may be amenable to DHA supplementation in predementia stages of AD. Evidence of accelerated DHA catabolism (eg, activation of phospholipases and oxidation pathways) could explain the lack of efficacy of ω-3 supplementation in AD dementia. The association of cognitive benefit with DHA supplementation in predementia but not AD dementia suggests that early ω-3 supplementation may reduce the risk for or delay the onset of AD symptoms in APOE4 carriers. Recent advances in brain imaging may help to identify the optimal timing for future DHA clinical trials. High-dose DHA supplementation in APOE4 carriers before the onset of AD dementia can be a promising approach to decrease the incidence of AD. Given the safety profile, availability, and affordability of DHA supplements, refining an ω-3 intervention in APOE4 carriers is warranted.
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影响因子：
5.3
作者：
Boehm-Cagan, Anat;Michaelson, Daniel M.
通讯作者：
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DOI：
10.1073/pnas.0308627101
发表时间：
2004-03-30
影响因子：
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作者：
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