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The urokinase plasminogen activator, PLAU, is a serine protease whose primary action is to convert the inactive zymogen plasminogen to plasmin, and plasmin is an Aβ degrading enzyme (reviewed by Tanzi and Bertram 2005

A NS SNP (rs2227564) from PLAU has been reported to be associated with LOAD (Finckh et al 2003 Ertekin-Taner et al 2005 However, our collaborators have carried out an association study of 8 SNPs from the PLAU gene, including rs2227564, in three samples sets: a case-control sample, discordant sib pairs and the original ASPs that generated the chromosome 10 linkage peak (Myers et al 2004 No association with any SNP was identified, and this lack of positive findings has been reported in additional studies (Bagnoli et al 2005 Papassotiropoulos et al 2004 Nonetheless, rs2227564 has been shown to be associated with an age-dependent increase of Aβ42 (Ertekin-Taner et al 2005 indicating that although variation in PLAU does not contribute to the chromosome 10 LOAD linkage peak (Myers et al 2004 it, like CTNNA3, affects plasma Aβ42 levels and may contribute to the linkage peak reported by Ertekin-Taner et al 2000

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