Department of Neuroscience, University of Genova, Genova, Italy.
J Alzheimers Dis. 2010;19(3):909-14. doi: 10.3233/JAD-2010-1285.
Mild cognitive impairment is often considered a transitional condition prodromal to Alzheimer's disease. The dissection of genetic risk factors predisposing to mild cognitive impairment is paramount to assess the individual predisposition and reliably evaluate the effectiveness of early therapeutic interventions. We designed a cross-sectional analysis to test whether the occurrence of mild cognitive impairment is influenced by variations of the tau protein gene. The genotypes of seven polymorphisms tagging the major tau haplotypes were assayed on 186 patients with amnestic mild cognitive impairment and 191 unrelated controls. Association study was conducted by logistic regression including APOE genotype and age as covariates. Case-control analysis showed that the common H1 haplotype is significantly overrepresented in patients (OR, 95% CI: 2.31, 1.52-3.51; p<0.001), whereas did not provide positive signals for any of the H1 sub-haplotypes that had been described as associated with Alzheimer inverted exclamation mark s disease. This finding was confirmed when the epsilon4 allele of the APOE gene was taken into account (OR, 95% CI: 2.319, 1.492-3.603; p<0.001). These results firstly suggest that the risk of mild cognitive impairment is influenced by tau protein gene variations and that mild cognitive impairment shares a common genetic background with Alzheimer's disease. They may help elucidating the genetic risk to cognitive decline and designing effective clinical trials.
轻度认知障碍通常被认为是阿尔茨海默病的前驱状态。剖析导致轻度认知障碍的遗传风险因素对于评估个体易感性和可靠评估早期治疗干预的效果至关重要。我们设计了一项横断面分析，以测试轻度认知障碍的发生是否受tau 蛋白基因变异的影响。在 186 名遗忘型轻度认知障碍患者和 191 名无关对照中，测定了七个标记主要 tau 单倍型的多态性的基因型。通过包含 APOE 基因型和年龄作为协变量的逻辑回归进行关联研究。病例对照分析表明，常见的 H1 单倍型在患者中明显过度表达（OR，95%CI：2.31，1.52-3.51；p<0.001），而对于任何已描述与阿尔茨海默病相关的 H1 亚单倍型均未提供阳性信号。当考虑 APOE 基因的 epsilon4 等位基因时，这一发现得到了证实（OR，95%CI：2.319，1.492-3.603；p<0.001）。这些结果首次表明，轻度认知障碍的风险受 tau 蛋白基因变异的影响，并且轻度认知障碍与阿尔茨海默病具有共同的遗传背景。它们可能有助于阐明认知衰退的遗传风险，并设计有效的临床试验。
