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

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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.