Year by year, our knowledge of the fundamental biology behind dementia is improving and with it, progress made on promising new therapeutics. What has become most evident is the need to target the earliest stages of diseases like Alzheimer’s, to maximise impact and save as much of the brain as possible. A growing area of interest is the specialised blood vessel network surrounding the brain, the blood-brain barrier (BBB), whose dysfunction and breakdown is thought to be one of the initial events in several neurodegenerative diseases.
To build a better understanding and explore opportunities for treatments in this area, Director at the UK DRI’s Centre at the University of Edinburgh, Prof Giles Hardingham is taking an integrated approach, bringing together specialist researchers and clinicians, and answering major questions at the intersection between our nervous, vascular and immune systems.
The BBB, like vasculature in the rest of the body, contains a layer of endothelial cells which line the inner tube of the vessels. However, due in part to ‘tight junctions’ between these cells, the BBB is extremely selective to maintain an optimised microenvironment needed for brain function. The specialisation continues with input from multiple other cell types: pericytes which regulate blood flow; neurons that send electrical messages across the brain; astrocytes that connect blood vessels and neurons to maintain metabolism; and microglia which are the resident brain immune cells. Together these cells serve a vital collective role in protecting the brain while helping it function correctly. As Dr Blanca Díaz-Castro, an expert on astrocyte biology, explains, there are still many challenges that remain in the field.
“There are fundamental questions that we need to answer in respect to the BBB. How is the integrity of the BBB maintained? How do BBB cells interact with each other? And what molecular pathways become dysfunctional in the earliest stages of disease? I believe that solving these will provide successful avenues for early diagnosis and treatment of dementia.”