Veterans Affairs Puget Sound Health Care System, Seattle,WA98108, USA.
JAMA Neurol. 2013 Feb;70(2):223-8. doi: 10.1001/jamaneurol.2013.600.
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). MAIN OUTCOME MEASURE The APOE allele frequencies. RESULTS 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 χ(2)(4)=185.25; 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). CONCLUSIONS 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.
检验载脂蛋白 E（APOE）ε4 等位基因与伴有神经原纤维缠结的突触核病性痴呆之间的关联。
遗传病例对照关联研究。
学术研究。
对尸检患者进行分类，分为 5 组：伴有高水平阿尔茨海默病（AD）神经病理改变（NCs）但无路易体病（LBD）NCs 的痴呆（AD 组；n=244），伴有 LBDNCs 和高水平 ADNCs 的痴呆（LBD-AD 组；n=224），伴有 LBDNCs 且无或低水平 ADNCs 的痴呆（单纯 DLB [pDLB] 组；n=91），无或低水平 ADNCs 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 等位基因频率明显高于对照组（7.2%；总 χ2(4)=185.25；P=5.56×10(-39)），pDLB 组明显高于 PDD 组（P=0.01）。在年龄和性别调整的显性模型中，ε4 与 AD（比值比，9.9；95%可信区间，6.4-15.3）、LBD-AD（比值比，12.6；95%可信区间，8.1-19.8）、pDLB（比值比，6.1；95%可信区间，3.5-10.5）和 PDD（比值比，3.1；95%可信区间，1.7-5.6）有很强的关联。
APOE ε4 等位基因是 LBD 谱中一种很强的危险因素，在 pDLB 中比 PDD 中更为常见。这表明，ε4 增加了在单纯突触核病中出现痴呆的可能性。pDLB 和 PDD 组的 ε4 频率升高，而这些组的总脑神经原纤维缠结负担较低，这表明 apoE 可能通过与淀粉样蛋白处理无关的机制促进神经退行性变。
