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

Background: Recently, a single point mutation in the presenilin 1 (PSEN1) gene of the first described Alzheimer's disease (AD) patient Auguste D was reported by Muller and co-workers. However, the sequencing results of the DNA from a 100-year-old tissue contained some uncertainties. Methods: We 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. Results: Our 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. Conclusion: Despite the wealth of data from Muller and co-workers, our results emphasize the requirement of more detailed analysis of Auguste D's DNA in future. (C) 2014 The Alzheimer's Association. All rights reserved.