Investigating the role the APOE in age-related neurovascular unit decline and neuroinflammation.
Age-related neurovascular unit decline and neuro-inflammation are hallmarks of many age-related neurodegenerative diseases but the mechanisms involved are not well understood. Further, these changes are not specific to the brain and vascular compromise and inflammation have been observed in other age-related diseases. Our overarching hypothesis is that age-related neurovascular compromise and neuro-inflammation predispose individuals to age-related cognitive decline and neurodegenerative diseases such as dementias.
In this pilot proposal, we will specifically test whether exercise can preserve/restore NVU decline and reduce neuro-inflammation in mice carrying no, one or two copies of human APOEε4. This will be important preliminary data to build a more comprehensive study assessing the role of exercise on specific APOE genotypes and age-related NVU decline and neuro-inflammation. For this pilot, we have two specific aims.
Aim 1: To determine the effect of exercise on activities of daily living and age-related cognitive decline in Apoeε4 mice.
Aim 2: To determine the effect of exercise on cellular and molecular processes in Apoeε4 mice