Blood-brain barrier permeability, inflammation, and clinical progression in Alzheimer’s disease

i. It is imperative that we undertake research into the causes of Alzheimer’s disease (AD). Also, the exploration of why some people with AD decline faster than others is an understudied area. The role of inflammation has been established as a key factor in the aetiology and progression of AD. The mechanism via which peripheral inflammation may cause neuroinflammation is likely to involve the blood-brain barrier (BBB). The BBB is vital in maintaining homeostasis in the brain. We have validated a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique that can detect subtle changes in BBB permeability. We will recruit 50 people with AD and 20 control participants into a clinical study to examine the role of BBB permeability and peripheral inflammation. We will determine their relationship with clinical progression by assessing people with AD over two years.

ii. Aims 1. To compare BBB permeability between AD and controls at baseline. 2. To analyse the relationship between BBB permeability and peripheral inflammation in AD at baseline. 3. To determine the relationship between BBB permeability at baseline and clinical progression in AD. 4. To identify whether BBB permeability at baseline and peripheral inflammation combine to affect clinical progression in AD.

iii. This research will enhance our understanding of the mechanisms by which BBB permeability and peripheral inflammation affect clinical progression in AD, thereby opening avenues for drug discovery and development. Our study will also determine whether DCE-MRI could be developed into a prognostic biomarker for AD.