The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.
The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease.
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DOI：
10.1186/s13195-016-0194-x
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发表时间：
2016-06-30
期刊：
影响因子：
--
通讯作者：
Schneider LS
中科院分区：
文献类型：
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作者：
Yassine HN;Rawat V;Mack WJ;Quinn JF;Yurko-Mauro K;Bailey-Hall E;Aisen PS;Chui HC;Schneider LS
载脂蛋白E（APOE）β 4和脑脊液（CSF）淀粉样蛋白-β42（Aβ42）水平低是阿尔茨海默病（AD）发生的预测因子。几项研究的结果表明，二十二碳六烯酸（DHA）的消费和APOE基因型的认知结果之间的相互作用。本研究的目的是在阿尔茨海默病合作研究赞助的DHA临床试验中，检查APOE β 4基因型和低CSF Aβ42水平是否与DHA向CSF的递送减少相关。在基线时，在384名参与者的血浆和70名参与者的CSF中测定了磷脂DHA。70名参与者中有44名在分配到安慰剂组（n = 15）或DHA组（n = 29）后完成了18个月的随访。在基线和18个月干预后测量血浆和CSF DHA水平、CSF Aβ42、Tau和磷酸化Tau。根据基线Aβ42 CSF水平将受试者分为三分位数。为了评估穿过血脑屏障的DHA递送，计算CSF与血浆DHA水平的比率。基线时，按CSF Aβ42三分位数或β 4状态划分的CSF或血浆磷脂DHA水平之间无显著差异。在补充DHA 18个月后，与其他三分位数相比，Aβ42最低三分位数的参与者CSF DHA水平显著降低（p = 0.01），CSF与血浆DHA比率显著降低（p = 0.05）。基线CSF Aβ42水平在104携带者中显著低于104非携带者（p = 0.01）。与非携带者（n = 4）相比，携带APOE 4等位基因的参与者（n = 25）的CSF DHA水平增加不太明显，治疗和APOE基因型之间可能存在相互作用（p = 0.07）。APOE β 4等位基因和较低的CSF Aβ42水平与DHA向CSF的转运较少相关。脑淀粉样蛋白病理学可能限制了AD患者DHA向脑的输送。Clinicaltrials.gov标识符：NCT 00440050。于2007年2月22日注册。
Apolipoprotein E (APOE) ɛ4 and low cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels are predictors for developing Alzheimer’s disease (AD). The results of several studies indicate an interaction between docosahexaenoic acid (DHA) consumption and cognitive outcomes by APOE genotype. Our objective in the present study was to examine whether APOE ɛ4 genotype and low CSF Aβ42 levels were associated with reduced delivery of DHA to CSF in the Alzheimer’s Disease Cooperative Study-sponsored DHA clinical trial. Phospholipid DHA was assayed in the plasma of 384 participants and CSF of 70 participants at baseline. Forty-four of the 70 participants completed the 18-month follow-up visit after allocation to placebo (n = 15) or DHA (n = 29). Plasma and CSF DHA levels, CSF Aβ42, Tau, and phosphorylated Tau were measured at baseline and after the 18-month intervention. Participants were divided into tertiles based on baseline Aβ42 CSF levels. To assess DHA delivery across the blood-brain barrier, the ratio of CSF to plasma DHA levels was calculated. At baseline, there were no significant differences between CSF or plasma phospholipid DHA levels by CSF Aβ42 tertiles or ɛ4 status. After 18 months of DHA supplementation, participants at the lowest Aβ42 tertile had significantly lower CSF DHA levels (p = 0.01) and lower CSF-to-plasma DHA ratios (p = 0.05) compared to the other tertiles. Baseline CSF Aβ42 levels were significantly lower in ɛ4 carriers than in ɛ4 noncarriers (p = 0.01). Participants carrying the ɛ4 allele (n = 25) demonstrated a less pronounced increase in CSF DHA level compared with noncarriers (n = 4), with a possible interaction effect between treatment and APOE genotype (p = 0.07). APOE ɛ4 allele and lower CSF Aβ42 levels were associated with less transport of DHA to CSF. Brain amyloid pathology may limit the delivery of DHA to the brain in AD. Clinicaltrials.gov identifier: NCT00440050. Registered on 22 Feb 2007.