Furthermore, increased levels of mature BDNF by administrating an inhibitor for plasminogen-activator inhibitor-1 (PAI-1, an inhibitor of plasmin-dependent conversion of pro-BDNF to mature BDNF) improved cognitive function and hippocampal amyloid burden in AD model mice that were overexpressing human amyloid precursor protein [88]. This evidence concerns the gene SERPINE1 and Alzheimer disease.