APOE ε4 increases risk for dementia in pure synucleinopathies.
APOE ε4 increases risk for dementia in pure synucleinopathies.
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DOI：
10.1001/jamaneurol.2013.600
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发表时间：
2013-02
期刊：
影响因子：
29
通讯作者：
Zabetian, Cyrus P.
中科院分区：
文献类型：
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作者：
Tsuang, Debby;Leverenz, James B.;Lopez, Oscar L.;Hamilton, Ronald L.;Bennett, David A.;Schneider, Julie A.;Buchman, Aron S.;Larson, Eric B.;Crane, Paul K.;Kaye, Jeffrey A.;Kramer, Patricia;Woltjer, Randy;Trojanowski, John Q.;Weintraub, Daniel;Chen-Plotkin, Alice S.;Irwin, David J.;Rick, Jacqueline;Schellenberg, Gerard D.;Watson, G. Stennis;Kukull, Walter;Nelson, Peter T.;Jicha, Gregory A.;Neltner, Janna H.;Galasko, Doug;Masliah, Eliezer;Quinn, Joseph F.;Chung, Kathryn A.;Yearout, Dora;Mata, Ignacio F.;Wan, Jia Y.;Edwards, Karen L.;Montine, Thomas J.;Zabetian, Cyrus P.
检测载脂蛋白E（APOE）ε4等位基因与痴呆伴突触核蛋白病的相关性。遗传病例对照关联研究。学术研究。尸检对象分为5类：痴呆伴高水平阿尔茨海默病（AD）神经病理学改变（NC），但无路易体病（LBD）NC（AD组; n=244），痴呆伴LBDNF和高水平ADNC（LBD-AD组; n=224），痴呆伴LBDNF和无或低水平ADNC（纯DLB [pDLB]组; n=91）、没有或低水平ADNC的帕金森病痴呆（PDD）（n=81）和对照组（n=269）。APOE等位基因频率AD（38.1%）、LBD-AD（40.6%）、pDLB（31.9%）和PDD（19.1%）组的APOE ε4等位基因频率显著高于对照组（7.2%;总体; P=5.56×10−39），pDLB组高于PDD组（P= 0.01）。在年龄校正和性别校正显性模型中，ε4与AD（比值比，9.9; 95%CI，6.4-15.3）、LBD-AD（比值比，12.6; 95%CI，8.1-19.8）、pDLB（比值比，6.1; 95%CI，3.5-10.5）和PDD（比值比，3.1; 95%CI，1.7-5.6）强相关。APOE ε4等位基因是LBD谱中的一个强风险因素，并且相对于PDD，在pDLB中的发生频率增加。这表明ε4增加了在纯突触核蛋白病的背景下表现为痴呆的可能性。pDLB和PDD组中ε4频率升高，其中总体脑神经炎斑块负荷较低，表明apoE可能通过与淀粉样蛋白加工无关的机制促进神经变性。
To test for an association between the apolipoprotein E (APOE) ε4 allele and dementias with synucleinopathy. Genetic case-control association study. Academic research. Autopsied subjects were classified into 5 categories: dementia with high-level Alzheimer disease (AD) neuropathologic changes (NCs) but without Lewy body disease (LBD) NCs (AD group; n=244), dementia with LBDNCs and high-level ADNCs (LBD-AD group; n=224), dementia with LBDNCs and no or low levels of ADNCs (pure DLB [pDLB] group; n=91), Parkinson disease dementia (PDD) with no or low levels of ADNCs (n=81), and control group (n=269). The APOE allele frequencies. The APOE ε4 allele frequency was significantly higher in the AD (38.1%), LBD-AD (40.6%), pDLB (31.9%), and PDD (19.1%) groups compared with the control group (7.2%; overall ; P=5.56×10−39), and it was higher in the pDLB group than the PDD group (P=.01). In an age-adjusted and sex-adjusted dominant model, ε4 was strongly associated with AD (odds ratio, 9.9; 95% CI, 6.4–15.3), LBD-AD (odds ratio, 12.6; 95% CI, 8.1–19.8), pDLB (odds ratio, 6.1; 95% CI, 3.5–10.5), and PDD (odds ratio, 3.1; 95% CI, 1.7–5.6). The APOE ε4 allele is a strong risk factor across the LBD spectrum and occurs at an increased frequency in pDLB relative to PDD. This suggests that ε4 increases the likelihood of presenting with dementia in the context of a pure synucleinopathy. The elevated ε4 frequency in the pDLB and PDD groups, in which the overall brain neuritic plaque burden was low, indicates that apoE might contribute to neurodegeneration through mechanisms unrelated to amyloid processing.
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影响因子：
6.4
作者：
Leverenz, James B.;Hamilton, Ronald;Montine, Thomas J.
通讯作者：
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Aarsland, D;Andersen, K;Kragh-Sorensen, P
通讯作者：
Kragh-Sorensen, P
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30.8
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