Combination effect of bradycardia, ApoE4 allele and increased vessel stiffness.

<p>(A) Having both bradycardia and the ApoE4 allele led to elevated levels of Aβ40 deposition in both the brain parenchyma and the cerebral vessels, with nearly a two-fold increase in Aβ40 in the cerebral vessels. There was a small decrease in the number of neurons at the final simulation endpoint (<10%). (B) In the case where the simulated patient was supposed to have cardiovascular disease (represented by increased vessel stiffness) and carry the ApoE4 allele, Aβ deposition was significantly elevated within the brain parenchyma (100x and 1000x for Aβ40 and Aβ42, respectively). The decreased levels of Aβ within the cerebrovasculature was not quite as significant as with increased vessel stiffness alone, suggesting that the ApoE allele plays an important role in determining deposition and Aβ concentration within the space near cerebral vessels. The significantly elevated Aβ levels led to a decrease in the neuronal cell number secondary to increased neuronal death rate seen at high Aβ levels. (C) The results of increased vessel stiffness in the presence of bradycardia led to results that were similar to those seen with increased vessel stiffness alone.