Different Age Related Neurological and Cardiac Effects of Verapamil on a Transgenic Mouse Model of Alzheimer's Disease.

Abstract

Dementias are the third cause of the disability-adjusted life-years (DALYs) worldwide with Alzheimer’s (AD) having the highest prevalence. Despite ample research in the field, therapeutic options are limited. However, with the increase in lifespan, a larger number of AD patients will receive other medication for the evermore-increased number of comorbidities that such patients face. The purpose of this study was to evaluate the neurological and cardiac effects of verapamil, on C57BL/6J-TgN (Thy1-APPKM670/671NL; Thy1-PS1L166P (APP) mice. The daily administration of 3.5mg/kg of verapamil for 28 days revealed different effects on young and aged APP mice. While young animals showed less anxiety and improved short-term memory with minimal cardiac effects (an increase in the duration of ventricular depolarization), aged ones did not present behavioral improvements, but with a decrease in the duration of ventricular depolarizing. Repolarization effects of verapamil were similar in young and aged animals, except for the duration of the ST segment that was longer in aged animals. Considering our results, the use of calcium blockers in AD patients should take into consideration the stage of the disease, as different effects could be seen at different stages of AD, in our model.