Sildenafil is used to treat erectile dysfunction under the name Vaagra and is also used to treat pulmonary arterial hypertension under the name Levatio. However, through a large-scale database analysis study it was confirmed that sildenafil reduces the risk of Alzheimer’s disease by more than 50%.
Sildenafil inhibits the activity of an enzyme called PDE-5, dilating the blood vessels around the penis and helping to achieve an erection. Recently, it has been suggested that it helps improve cognition and memory by reducing excessive phosphorylation of the tau protein, which is believed to cause Alzheimer’s disease.
However, not all studies have confirmed the effectiveness of sildenafil in preventing Alzheimer’s disease, and the mechanism is not well known. The research team at the Cleveland Clinic in the US conducted a parallel analysis using a large patient database and an experiment using cells cultured from iPS cells derived from Alzheimer’s disease patients.
First, the research team analyzed millions of anonymized insurance claims data in two databases and compared the risk of Alzheimer’s disease between patients taking sildenafil and those not taking it. As a result, after adjusting for Alzheimer’s disease risk factors such as gender, age, and disease, it was found that taking sildenafil reduced the risk of Alzheimer’s disease by 30-54%. The Alzheimer’s disease risk-reducing effect is said to have been confirmed in patients who took sildenafil as treatment for pulmonary arterial hypertension.
To study the effect of sildenafil on nerve cells, the research team differentiated iPS cells derived from patients with Alzheimer’s disease into brain nerve cells. Cultured neurons derived from Alzheimer’s disease patients accumulated a large amount of abnormally phosphorylated tau protein compared to cultured neurons derived from non-Alzheimer’s patients.
When nerve cells derived from Alzheimer’s disease patients were treated with sildenafil for 5 days, abnormally phosphorylated tau protein was significantly reduced. Furthermore, changes in the expression of hundreds of genes linked to the neurodegeneration of Alzheimer’s disease, including inflammation and interneuronal communication, were observed in nerve cells treated with sildenafil. However, more research is needed to determine exactly how the changes sildenafil brings affect Alzheimer’s disease.
The research team found it gratifying to be able to computationally integrate such a large amount of data to see the effects of sildenafil on human neurons and actual patient outcomes. He said he would provide the necessary evidence. Related information can be found here.
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