PAI-1 expression inhibits both tPA and uPA and their activity, thus decreasing the level of plasmin.[35] The 4G/5G polymorphism, which is located at the transcription site of the PAI-1 gene, is responsible for increased PAI-1 expression.[11] Thus, the PAI-1 4G/5G polymorphism may be associated with the pathogenesis of AD. This evidence concerns the gene SERPINE1 and Alzheimer disease.