The N141I mutation in PSEN2: implications for the quintessential case of Alzheimer disease

Abstract

Objective: To connect a new family with early-onset Alzheimer disease (EOAD) in Germany to the American Volga German pedigrees.

Design: Pedigree molecular genetic analysis.

Setting: University Medical Centers in Fulda and Giessen, Germany, and in Seattle, Washington.

Results: The families from Fulda, Germany, and the American Volga German families with EOAD share the same N141I PSEN2 mutation on an identical haplotypic background. This establishes that the N141I mutation occurred prior to emigration of the families from the Hesse region to Russia in the 1760s, and documents that relatives of the original immigrant families are presently living in Germany with the mutation and the disease.

Conclusion: A family with the N141I mutation in PSEN2 that presently lives in Germany has been connected to the haplotype that carries the same mutation in pedigrees descended from the Volga Germans. This raises the possibility that the original patient with Alzheimer disease (Auguste D.), who had EOAD and lived in this same region of Germany, may also have had the PSEN2 N141I mutation.

Figure

Tagging single-nucleotide polymorphisms (SNPs) for PSEN2 haplotype analysis.