A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease
2006 | journal article. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease
Riemenschneider, M.; Konta, L.; Friedrich, P.; Schwarz, S.; Taddei, K.; Neff, F. & Padovani, A. et al. (2006)
Human Molecular Genetics, 15(16) pp. 2446-2456. DOI: https://doi.org/10.1093/hmg/ddl167
Documents & Media
Details
- Authors
- Riemenschneider, Matthias; Konta, Lidija; Friedrich, Patricia; Schwarz, Sandra; Taddei, Kevin; Neff, Frauke; Padovani, Alessandro; Koelsch, Heike; Laws, Simon M.; Klopp, Norman; Bickeboeller, Heike ; Wagenpfeil, Stefan; Mueller, Jakob C.; Rosenberger, Albert ; Diehl-Schmid, Janine; Archetti, Silvana; Lautenschlager, Nicola; Borroni, Barbara; Mueller, Ulrich; Illig, Thomas; Heun, Reinhard; Egensperger, Rupert; Schlegel, Juergen; Foerstl, Hans; Martins, Ralph N.; Kurz, Alexander
- Abstract
- A number of susceptibility loci for Alzheimer's disease (AD) have been identified including a region on Chromosome 10q21-q22. Within this region the plasminogen activator urokinase gene (PLAU) was considered as a reasonable candidate from its functional implication in plasmin generation, a serine protease capable of degrading beta-Amyloid (A beta) protein. We screened 56 single nucleotide polymorphisms (SNPs) around PLAU using 1751 individuals from four independent case-control samples (Munich, N=679; Bonn N=282; Brescia (Italy) N=219; Perth (Australia) N=557 and one discordant sib-pair sample (Munich N=622). In brain tissue samples of neuropathologically confirmed cases with AD (N=33) we analyzed plaque counts according to the risk allele. We identified that one functional exonic SNP (rs2227564) is associated with development of AD using the four independent case-control samples (Munich, P=0.02; Bonn, P=0.005; Brescia (Italy), P=0.001; Perth (Australia), P=0.03) and the discordant sib-pair sample (P=0.001). In brain tissue, from neuropathologically confirmed cases with AD, we identified significantly higher plaque counts in carriers of the risk allele (N=6; 60.3 +/- 16.9) compared with non-carriers (N=9; 26.3 +/- 8.8; P=0.007). This study provides compelling evidence of a genetic and functional involvement of a common PLAU variant into the pathogenesis of AD. Further functional investigations are warranted to elucidate the specific role of PLAU, respectively, PLAU variants in the metabolism of A beta proteins.
- Issue Date
- 2006
- Status
- published
- Publisher
- Oxford Univ Press
- Journal
- Human Molecular Genetics
- ISSN
- 0964-6906