Kasuga K, Shimohata T, Nishimura A, Shiga A, Mizuguchi T, Tokunaga J, Ohno T, Miyashita A, Kuwano R, Matsumoto N, Onodera O, Nishizawa M, Ikeuchi T
Department of Molecular Neuroscience, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata, Japan.
J Neurol Neurosurg Psychiatry. 2009 Sep;80(9):1050-2. doi: 10.1136/jnnp.2008.161703.
The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined.
The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients.
We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls.
Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.
在患有早发性家族性阿尔茨海默病（EO-FAD）和脑淀粉样血管病的欧洲家族中，已描述了淀粉样前体蛋白基因（APP）重复的发生情况。然而，APP重复在其他种族人群的AD发生发展中的作用仍未确定。
通过定量PCR和基于微阵列的比较基因组杂交分析，检测了日本人群中25个患有家族性AD（FAD）的家族的先证者和11例散发性早发性AD（EO-AD）病例中APP重复的发生情况。使用从患者外周血中提取的mRNA，通过实时定量逆转录（RT）PCR分析确定APP表达水平。
我们在两个不相关的EO-FAD家族中鉴定出APP基因座重复。这些家族中两名患者的重复基因组区域彼此不同。在晚发性FAD家族或散发性EO-AD患者中未发现APP重复。APP重复的患者在五十多岁时出现隐匿性记忆障碍，无脑出血和癫痫。定量RT-PCR分析显示，与年龄和性别匹配的对照组相比，这些患者的APP mRNA表达水平升高。
我们的结果表明，对于不同种族的EO-FAD患者应考虑APP重复情况，并且由于APP重复导致的APP mRNA表达水平升高有助于AD的发生发展。
