APOE ε 4 allele and CSF APOE on cognition in HIV-infected subjects.
APOE ε 4 allele and CSF APOE on cognition in HIV-infected subjects.
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DOI：
10.1007/s11481-010-9254-3
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发表时间：
2011-09
期刊：
影响因子：
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通讯作者：
Chang L
中科院分区：
文献类型：
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作者：
Andres MA;Feger U;Nath A;Munsaka S;Jiang CS;Chang L
目前尚不清楚脑脊液载脂蛋白E水平的意义以及载脂蛋白Eε4等位基因(S)的存在是否会对脑功能产生不同程度的影响。然而，载脂蛋白Eε4等位基因与更高的艾滋病毒相关性痴呆的发生率和艾滋病毒感染的加速进展有关。在这里，我们展示了载脂蛋白ε4在促进认知障碍中的作用的进一步证据。我们测量了HIV感染者脑脊液中的载脂蛋白E水平。HIV感染者的脑脊液载脂蛋白含量低于SN对照组(−为19%，p=0.03)。ε4等位基因携带者和无ε4等位基因携带者的脑脊液载脂蛋白E水平无明显差异，但ε4+−阳性携带者的脑脊液载脂蛋白E水平高于SLE携带者(+34%，P=0.0 1)。此外，携带ε2或ε3等位基因的ε+受试者(S)的脑脊液载脂蛋白水平与其在加工速度领域的认知表现呈正相关(r=+0.35，p=0.0 5)，而携带脑脊液载脂蛋白E(4)水平的受试者则表现出负相关关系，表现为脑脊液载脂蛋白E(4)水平较高者在艾滋痴呆量表上的表现较差(r=−0.61，p=0.0 2)，整体认知得分较低(r=−0.5 7，p=0.0 3)，在涉及学习的测试中表现较差(ε4等位基因×[apoe]交互作用，p=0.0 1)。我们的研究结果还表明，ε4+ε+中相对较高的脑脊液载脂蛋白E水平(主要是APOE4亚型)可能会对大脑产生负面影响，导致较差的认知结果，而那些没有APO4等位基因(主要是APOE2或APOE3亚型)的个体可能会出现代偿反应，从而导致更好的认知表现。
The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE ε4 allele(s) in HIV-infected patients are unknown. However, APOE ε4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE ε4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (−19%, p=0.03). While SN subjects with or without ε4 allele showed no difference in CSF APOE levels, ε4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε4− HIV+ subjects (+34%, p=0.01). Furthermore, while HIV+ subjects with ε2 or ε3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r=+0.35, p=0.05), ε4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r=−0.61, p=0.02), had lower Global Cognitive Scores (r=−0.57, p=0.03), and had poorer performance on tests involving learning (ε4 allele × [APOE] interaction, p=0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.