Mutations in RNA: a first example of molecular misreading in Alzheimer's disease

In the past decade, considerable progress has been made in the understanding of the neurodegenerative changes that occur in Alzheimer's disease (AD). Knowledge about this disease is based mainly on studies of inherited forms of AD, although most cases of AD are of the non-familial type. Recently, a novel type of mutation in 'vulnerable' dinucleotide repeats in messenger RNA was discovered in AD patients: in this type of mutation a mutated transcript is produced from a correct DNA sequence, a process that we call 'molecular misreading'. The resulting mutated '+1 proteins' are prominent neuropathological hallmarks of AD and they are present in most elderly non-demented people also. This suggests that the dinucleotide deletions in transcripts could be one of the earliest events in the neuropathogenesis of AD and an important factor in normal aging.