Background: As we age, our blood vessels (“vasculature”) can become damaged, leading to a lack of oxygen and nutrients being supplied to the brain. Such vascular damage can increase the risk of Alzheimer’s disease (AD) by up to three times. The brain has specialized immune cells, called astrocytes and microglia, that regulate healthy blood flow. However, in AD, the immune cells become overactive. This immune activation can increase the formation of vascular lesions, altering blood flow. However, up to date, little attention has been given to how immune and vascular cells interact with each other to impact brain changes and, in turn, cognition in people living with AD.

Objectives: This study aims to fill this knowledge gap by investigating the impact of vascular-immune interactions on brain changes and the type of symptoms that individuals living with AD develop.

Methods: We will identify signs of vascular disease on MRI scans, and immune activation patterns on PET images and via blood samples. We will study 3 independent populations totaling 538 individuals across different disease stages. We will then analyze how vascular and immune biomarkers at the start of the study can affect the development of AD brain changes and memory problems at later time points (up to 3 years).

Impact: Targeting excessive immune reactions in the brain could slow down AD from progressing. But in order to achieve that, we first have to understand how the brain’s vascular-immune interactions impact the disease course. Our study presents a unique and more detailed picture of key and understudied mechanisms driving AD. This will open up new perspectives on the development of personalized treatment strategies targeting the interface between the vascular system, brain immune cells, and AD.