APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease.
APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease.
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DOI：
10.18632/aging.101203
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发表时间：
2017-03-23
期刊：
影响因子：
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通讯作者：
Bachmeier C
中科院分区：
文献类型：
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作者：
Abdullah L;Evans JE;Emmerich T;Crynen G;Shackleton B;Keegan AP;Luis C;Tai L;LaDu MJ;Mullan M;Crawford F;Bachmeier C
本研究旨在探讨载脂蛋白E （APOE）对血磷脂（PL）在预测临床前阿尔茨海默病（AD）中的作用。脂质组学分析还对表达人类APOE亚型（EFAD）和5种AD突变的AD小鼠模型和195名认知正常的参与者的血液进行了分析，其中23人在3年内转化为轻度认知障碍(MCI)/AD。与认知正常的ε4和非ε4携带者相比，APOE ε4携带者转化为MCI/AD的PL中花生四烯酸(AA)/二十二碳六烯酸（DHA）比值较高。含有PL种的花生四烯酸和DHA、ε4-status和a - β42/ a - β40比值检测MCI/AD的准确率为91%。即使在ε4携带者中，鱼油/ ω -3脂肪酸的摄入也与较低的AA/DHA比率相关。与其他亚型EFAD小鼠相比，E4FAD小鼠血浆AA/DHA比值较高。特别是，与E3FAD小鼠相比，E4FAD小鼠的大脑中也观察到血浆中含有PL的AA和DHA的变化。尽管样本量小，随访时间短，但这些结果表明，血液PL可能作为临床前MCI/AD的生物标志物。
This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers. Arachidonic acid and DHA containing PL species, ε4-status and Aβ42/Aβ40 ratios provided 91% accuracy in detecting MCI/AD. Fish oil/omega-3 fatty acid consumption was associated with lower AA/DHA ratios even among ε4 carriers. High plasma AA/DHA ratios were observed in E4FAD compared to EFAD mice with other isoforms. In particular, alterations in plasma AA and DHA containing PL species were also observed in the brains of E4FAD mice compared to E3FAD mice. Despite the small sample size and a short follow-up, these results suggest that blood PL could potentially serve as biomarkers of preclinical MCI/AD.