Genetics of Sporadic AD

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Currently, we run a joint project with two Latvian research groups at the Organic Synthetis Institute (OSI) and the University of Latvia (LU) to investigate whether amino acid changes in the Abeta peptide could be exploited as an innovative method to dissolve higher order Abeta aggregates and to enhance clearance of Abeta from the brain to the blood stream. This project is based on investigations of the genetics in an Italian family. Researchers discovered (DeFede et al.) specific amino acid changes in the N-terminal part of Abeta that lead to the protection of heterozygote carriers by reducing the aggregation propensity.

Furthermore, studies have shown that the risk to suffer from AD is increased by a maternal genetic load. As mitochondrial DNA (mtDNA) is inherited only maternally, it is likely that mutations in mtDNA are the cause for this fact. Our investigations revealed that mtDNA influences the AD pathology. Therefore, further research on the genetic aspects of AD is needed.

* Project Links:

Read more … JPND NeuroGEM project

Published Research Papers:

  • Impaired mitochondrial energy production and ABC transporter function – a crucial interconnection in dementing proteopathies of the brain.
    Mech Ageing Dev (2013)

    Pahnke J, Fröhlich Ch, Krohn M, Schumacher T, Paarmann K
    Oct 134(10):506-15. PubMed PDF

  • Mitochondrial DNA polymorphisms specifically modify cerebral ß-beta-amyloid proteostasis.
    Acta Neuropath (2012)

    Scheffler K*, Krohn K*, Dunkelmann T, Stenzel J, Miroux B, Ibrahim S, von Bohlen und Halbach O, Heinze HJ, Walker LC, Gsponer JA, Pahnke J
    Aug 124(2):199-208. PubMed PDF