National Reference Center for TSE Surveillance at Department of Neurology, University Medical School, Göttingen, Germany.
J Alzheimers Dis. 2011;23(4):717-26. doi: 10.3233/JAD-2010-101527.
The presence of apolipoprotein E (ApoE) ε4 allele is a risk factor for Alzheimer's disease (AD) and associated with a more pronounced reduction of amyloid-β 1-42 (Aβ1-42) in the cerebrospinal fluid (CSF). Because a decrease of Aβ1-42 and increase of tau protein levels, both important biomarkers for AD, are also reported in Creutzfeldt-Jakob disease (CJD), we analyzed if a similar relationship can be observed in this rapid progressive dementia. Our study included 309 patients with sporadic CJD (147 neuropathologically confirmed and 162 probable cases). We analyzed the role of ApoE ε4 in sporadic CJD (sCJD), in particular the influence on the CSF-markers 14-3-3 protein, tau protein, neuron-specific enolase, S100 protein, Aβ1-42, and Aβ1-40. No differences in the ApoE ε4 allele frequency and ApoE genotype distribution between sCJD and published healthy controls were observed. The ApoE ε4 allele had no effect on disease duration or age at onset. We detected a dose-dependent ApoE ε4 effect on the decrease of Aβ1-42 in sCJD. ApoE ε4 carriers with one ApoE ε4 allele showed significantly reduced Aβ1-42 values (p < 0.0001) in comparison with non-carriers. ApoE ε4 allele is not a risk factor for sCJD but modifies the Aβ1-42 levels in CSF in a similar manner as in AD. Based on our results in sCJD patients, we hypothesize that the ApoE ε4 effect on Aβ1-42 values might not be disease-specific.
载脂蛋白 E（ApoE）ε4 等位基因的存在是阿尔茨海默病（AD）的危险因素，与脑脊液（CSF）中淀粉样蛋白-β1-42（Aβ1-42）的明显减少有关。由于 Creutzfeldt-Jakob 病（CJD）也报道了 Aβ1-42 和 tau 蛋白水平的降低，这两者都是 AD 的重要生物标志物，我们分析了在这种快速进展性痴呆中是否也可以观察到类似的关系。我们的研究包括 309 例散发性 CJD 患者（147 例经神经病理学证实，162 例可能病例）。我们分析了 ApoE ε4 在散发性 CJD（sCJD）中的作用，特别是对 CSF 标志物 14-3-3 蛋白、tau 蛋白、神经元特异性烯醇化酶、S100 蛋白、Aβ1-42 和 Aβ1-40 的影响。在 sCJD 和已发表的健康对照组之间，ApoE ε4 等位基因频率和 ApoE 基因型分布没有差异。ApoE ε4 等位基因对疾病持续时间或发病年龄没有影响。我们在 sCJD 中检测到 ApoE ε4 等位基因对 Aβ1-42 降低的剂量依赖性效应。与非携带者相比，携带一个 ApoE ε4 等位基因的 ApoE ε4 携带者 Aβ1-42 值显著降低（p < 0.0001）。ApoE ε4 等位基因不是 sCJD 的危险因素，但以与 AD 相似的方式修饰 CSF 中的 Aβ1-42 水平。基于我们在 sCJD 患者中的结果，我们假设 ApoE ε4 对 Aβ1-42 值的影响可能不是疾病特异性的。
