Short ReportA presenilin 1 mutation in the first case of Alzheimer's disease: Revisited

BackgroundRecently, a single point mutation in the presenilin 1 (PSEN1) gene of the first described Alzheimer's disease (AD) patient Auguste D was reported by Müller and co-workers. However, the sequencing results of the DNA from a 100-year-old tissue contained some uncertainties.MethodsWe heat extracted DNA from an original histological slice of Auguste D's brain and used nested polymerase chain reaction for the amplification of different exons of genes known to be affected in familial forms of AD.ResultsOur sequencing analysis did not validate the reported mutation. Furthermore, an extended sequencing analysis of Auguste D's DNA revealed no indication of a nonsynonymous hetero- or homozygous mutation in the exons of APP, PSEN1, and PSEN2 genes comprising the already known familial AD mutations.ConclusionDespite the wealth of data from Müller and co-workers, our results emphasize the requirement of more detailed analysis of Auguste D's DNA in future.