Analysis of blood vessel networks in Alzheimer’s Disease model mice
With two recent high-profile failures of promising treatments to Alzheimer’s Disease (AD) in Phase III clinical trials (Bapineuzumab, Solanezumab) which targeted amyloid β plaques occurring in AD, there has been a revival of basic research toward new targets and pathologies relevant to the disease. Toward these efforts, there has been much interest in examining the roles of inflammation and the roles of blood vessel networks in contributing to AD. It is believed that changes in and damage to blood vessel networks in the brains of AD patients contribute to AD-related dementia.
Quantification of changes in the tortuosity of blood vessel networks in AD mouse models was conducted utilizing immunolabeling and 3D imaging of 1 mm mouse brain sections. Reconstruction of the blood vessel network in 3D allowed for analysis of branching patterns and branch length, which provided quantitative measures of alterations in the blood vessel networks in the triple transgene 3xTg AD mouse models compared to BALB/cJ mouse brains.
Tortuosity is a measure of how curved a blood vessel is, calculated for this work as the ratio of the branch length to the distance between the branch’s endpoints. Increasing tortuosity results in less efficient blood flow through the vessels, since more linear distance must be traveled to reach the endpoint of a vessel. The average blood vessel tortuosity in the brain of mice is approximately 1.2, meaning that the ratio of the branch length to the distance between the ends of the branches is approximately 5 to 4. Significant differences in the blood vessel network were detected between BALB/cJ and 3xTg mouse models.