Association studies between the plasmin genes and late-onset Alzheimer's disease |
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Authors: | Shibata Nobuto Kawarai Toshitaka Meng Yan Lee Joseph H Lee Hye-Seung Wakutani Yosuke Shibata Eri Pathan Nazia Bi Andrew Sato Christine Sorbi Sandro Bruni Amalia C Duara Ranjan Mayeux Richard Farrer Lindsay A George-Hyslop Peter St Rogaeva Ekaterina |
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Affiliation: | Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto and Toronto Western Hospital Research Institute, Toronto, Ontario, Canada. |
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Abstract: | The plasmin system is involved in the degradation of Abeta peptides, the accumulation of which in brain is a hallmark of Alzheimer's disease (AD). In a North European case-control AD dataset we studied 14 common variations in the PLG, PAI-1, PLAT and PLI genes encoding components of the plasmin system. Among the four polymorphisms in the PLAT, PAI-1 and PLI genes showing nominally significant evidence for an association with AD (allele p-value=0.01-0.00003) the strongest association was detected for the deletion allele in the Alu-repeat region of the PLAT gene. However, none of these positive results were confirmed in follow-up studies using an independent Canadian case-control cohort and two familial AD datasets of North European and Caribbean Hispanic origin. Thus, the current survey does not support the notion that common polymorphisms in the plasmin genes influence the development of AD. |
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