Research Brief: Auguste D.'s Mutation Identified – Alzforum: News

Research: Auguste D. 'S mutation identified - Alzforum: News
Tags: empress transcontinental railway 20th May 2010. Add the last pages of anthropological mystery recommend that the scientists in recent months, Archives of Neurology, which is highly possible that Auguste Deter, the first patient of Alzheimer's disease identified, carried the mutation N141I presenilin-2 the same as in the current Member States, U.S. families, descendants of German immigrants who settled near the Volga River in Russia. Based on new data in molecular genetics, Thomas Vogel, University of Washington, Seattle, and his colleagues suspect that the descendants of the Volga Germans and a German family today in a state of discouraging membership, Hesse, the proportion of this mutation PS2, like a piece of of a chromosome that surrounds it. This means that it is very likely to have a common ancestor, "said Bird ARF. We believe that there are indications interesting historical, social, geographical and genetic Alzheimer's patients showed this mutation may also original.
More than 20 years old, the laboratory birds came about a handful of German-American families with early onset AD and a number of common surnames. Scientists continue to find these 11 families and all to a single ethnic group track, the Volga Germans who lived in or near today in Frankfurt am Main, Germany. Lured by the Russian Empress Catherine the Great of the country and offers the guarantee of their German roots and the Russian draft-avoidance maintain families migrated to the end of 1770 the Volga region of Russia. They lived there in relative social isolation, and genetics. When push came, some came in the U.S. 1880-1920 in search of economic space and the opportunities that came with the building of transcontinental railroads in the Great Plains. Their descendants eventually became known, Bird and colleagues, these families come from an autosomal dominant gene from a single ancestor (Bird et al speculated inherited., 1988). We thought that probably represented a genetic founder effect, "said Bird.
Your intuition was correct. All 11 families had identified the same mutation in PS2 (Levy-Lahad et al., 1995), the gene for early onset with the lowest number of pathogenic mutations current AD. (See Jayadev et al. Combined in 2010 for a complete analysis of the genotypes and phenotypes with mutations in the PS2.) Knowing that Auguste D., Alois Alzheimer's original patients, in the Frankfurt area and developed early-onset around the age of 50 years lived , like the Volga German families asked, Bird and colleagues, whether he had the same mutation PS2. Its quite possible that this woman is an ancestor of some of the Volga German families who had remained in Germany, "said Bird. But we do not have any evidence.
Since then, several developments reinforced their hypothesis newborns. The first came in 1995 when a team of doctors in a curiously intact University of Monaco of Bavaria-Keller a photo of the Alzheimer's disease AD, his original notes on them, and brain tissue taken at autopsy. The analysis of DNA from the fabric of their histopathological slides have shown researchers that Auguste D. did not have the ApoE4 allele in late-onset AD risk (in fact, was homozygous for ApoE3), and that the APP gene was AD not known mutations (Graeber et al. 1997; Graeber et al., 1998). Had begun to presenilin mutations screening, but due to the limited availability of tissue, based on the analysis when the camp a deeper understanding of the genetic defect was AD.
While ApoE and APP results were consistent with the idea that Auguste D. had the PS2 N141I mutation, a crucial piece of evidence was still arise. If our hypothesis is correct, Vogel said, someone should be included with the mutation in modern Germany.
In 2008, scientists have for the first time a family, lives in Sydney reported to cause early-onset of PS2-N141I mutation (AD et al Nikisch., 2008). We thought this was one of the missing links, "said Bird ARF. One case was published in Germany said today that there are people left in Germany who have this mutation. Bird took this as further evidence that the original cause of Alzheimer's disease-one was left behind.
For additional evidence has lead author Chang-En Yu and colleagues, a haplotype analysis on a sample of DNA carried by the subject of the current German early-onset AD (EOAD) family. In comparison with the DNA of 130 people from the Volga-German pedigrees today, and showed that the markers flanking the chromosome mutation N141I were the same for all subjects. Not only have the same mutation, "said Bird, but theres a strong evidence that the same part of chromosome 1 This points to the same gene region was in this family separated in Hesse, as that of the Volga German families over the years, he said. The Auguste D. Hesse lived in the same region and had similar beginning with AD age (47 years vs. 55.5 years for American families Volga-Germans), also suggested that it could provide liaison between the family of today Hesse and the Volga Germans United States.
Top Volga German AD pedigrees to date comes from a family of Gary Reiswig, a retired city planner and lecturer at East Hampton, New York. Reiswig was 25 when he learned that his father had early-onset AD, as 10 of his 13 aunts and uncles took his father's side. Now 70, chronicles his experiences Reiswig familys with the disease in his recently published book, The Thousand Mile Stare see (ARF Related News story). Reiswig shares end-of-life stories of many families affected by similar descriptions of Auguste D. in the final stages of his illness.
Although this will not be added no scientific evidence, I believe that these observations could be more than just interesting coincidences, Reiswig said in an e-mail to ARF. He also noted a similarity between the family Auguste D. and his family (see full comment below).
But the ultimate proof that Auguste D. PS 2 N141I mutation had yet to come. The potential to prove and document that it is, "said Bird, who targeted mutation analysis of brain tissue from DS Auguste autopsy slides. He said that scientists in Germany, which have access to the samples previously extremely conservative control.
Meanwhile, researchers are just happy to have a family of early-onset AD to investigate, noting that the families were extremely difficult to find in-Esther Landhuis Germany..
Reference: CE Yu, Marchani E, G Nikisch, U Mller, Nolte D, Hertel A, Wijsman EM, Bird TD. The N141I mutation in PSEN2: Implications for the quintessential case of Alzheimer's disease. Arch Neurol. 2010 May, 67 (5) :631-3. Summary
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