A study for the contribution of RNA editing abnormality in sporadic Alzheimer's disease.

本研究旨在探索散发性阿尔茨海默病（AD）的新突变。我们在ALS患者中发现了rna编辑错误作为转录后修饰的发生。基于这一观察结果，我们研究了这种编辑错误是否是ALS以外的其他神经退行性疾病的潜在原因。阿尔茨海默病是一种常见的神经退行性疾病，其散发形式占全部病例的90%以上。我们研究了基因组序列，特别关注早老素1，淀粉样蛋白前体蛋白和nicastrin，因为这三个被确定为女性AD病例的主要致病基因。对感兴趣的基因进行反向转录，用特定引物扩增，编码三个基因并测序。我们分析了20多例病例，发现了几个SNP变化，但没有发现遗传改变与疾病发病之间的正相关。在这些病例中，我们观察到两个有趣的病例。其中一个有PS1 L153L突变。本病例为散发性病例，年龄90岁。可能这些病例不是由这种沉默的突变引起的，而是由正常的衰老引起的，因为它是非常晚发的。另一个病例是零星的，年轻的。他27岁。这个病例显示了PS1 L85P突变特别有趣的是它显示了视觉失认症以及痉挛性麻痹这在PS1突变的早发家族性AD病例中很常见。目前尚不清楚视觉失认症与PS1基因改变之间的关系，但值得进一步研究。

This study was performed on exploring new mutations in sporadic Alzheimer's disease (AD). We have found the occurrence of RNA-editing error as post-transcriptional modification in ALS patients. Based on this observation, we examined if such editing error is a potential cause for other neurodegenerating diseases than ALS. AD is well known to be one of popular neurodegenerating diseases and its sporadic forms occupy more than 90% of the whole cases. We studied genomic sequence particularly focusing on presenilin1, amyloid precursor protein and nicastrin because these three are established to the main causal genes for femilial AD cases. Genes of interest were reversed-transcribed, amplified with specific primers to encode three genes and sequenced. We analyzed more than 20 cases and found several SNP changes but failed to find the positive correlation between the genetic alteration and disease onset. Among these cases, we observed two interesting cases. One has the PS1 L153L mutation. This case was sporadic and 90 yr old. Probably the cases was not caused by this silent mutation but by normal aging because it is very late-onset. Another case was sporadic and young. He was 27 yr old. The case shows PS1 L85P mutation and particularly interesting because it shows visual agnosia as well as spastic paraparesis which was very common to early-onset familial AD cases with PS1 mutations. We do not know the relationship between visual agnosia and PS1 alteration but it is supposed to be worth to be examined in future.