Promoter polymorphisms of SERPINE1 are associated with the antidepressant response to depression in Alzheimer's disease.

Depression is one of the most frequent neuropsychiatric symptoms in Alzheimer's disease (AD). As the main regulator of the tissue plasminogen activator/brain-derived neurotrophic factor axis, plasminogen activator inhibitor-1 (PAI-1) is involved in the pathogenesis of both AD and depression. This suggests a potential role of the PAI-1 gene SERPINE1 in the development of AD-related depression and its response to antidepressant treatment. The purpose of this study was to explore the association between the SERPINE1 promoter polymorphisms (rs1799889 and rs2227631) and the risk of depression in AD and to determine the relationship between these 2 polymorphisms and the response to paroxetine treatment in AD patients with depressive symptoms. A total of 423 AD patients, all of which were inpatients, including 161 patients with obvious depressive symptoms, were recruited into this study, and the MassARRAY system was used for genotyping. We failed to detect any significant associations of these 2 polymorphisms with AD-related depression in the Chinese population (p>0.05). However, for the depressive symptoms in AD, the frequency of the 5G allele of rs1799889 was significantly higher (p=0.009 after Bonferroni correction) in responders than in non-responders to an 8-week paroxetine treatment. Our preliminary results suggest that the SERPINE1 promoter polymorphisms may be associated with antidepressant treatment, but not with the increased susceptibility to the depressive symptoms in AD.