Permeability of the blood-brain barrier in Alzheimer’s disease
Research type
Research Study
Full title
Permeability of the blood-brain barrier in Alzheimer’s disease (PEBBAL) measured using dynamic contrast-enhanced MRI: a pilot study
IRAS ID
280305
Contact name
Jay Amin
Contact email
Sponsor organisation
Southern Health NHS Foundation Trust
Duration of Study in the UK
1 years, 11 months, 28 days
Research summary
Research Summary:
Alzheimer's disease is the most common cause of dementia. There is no cure and we still don't fully understand why some people's symptoms worsen faster than others. We know that when people with dementia get infections their symptoms can get worse. Blood vessels normally block the entry of bacteria and chemical messengers into the brain, which if allowed to enter could cause damage to nerve cells. This defence is called the blood brain barrier (BBB).
A few research studies have measured how much of a chemical contrast moves from the blood into the brain using a Magnetic Resonance Imaging (MRI) brain scan, and suggested that the BBB may become leakier in dementia. We have developed a more accurate method to measure BBB leakiness, using these brain scans.
We are interested in how the BBB, immune system and dementia are linked. We believe that with our improved method of measuring BBB leakiness, we can more accurately measure BBB leakiness in people with Alzheimer's disease, and potentially predict those people with Alzheimer’s disease who may get worse more quickly.
People with Alzheimer's disease and people without dementia will be assessed in a research clinic and have an MRI brain scan. Blood and urine samples will be used to examine the immune system. People with Alzheimer's disease will then be observed again one year later to measure how much their symptoms have worsened.Summary of Results:
The causes of Alzheimer’s disease (AD) are poorly understood. Infections can cause symptoms to worsen for people with AD. Infections activate the immune system in the blood, a process called inflammation. Inflammation can send signals to the brain that cause damage to nerve cells, leading to worsening memory. How this signal enters the brain could explain why some people with AD decline faster than others.
The blood-brain barrier is a lining around the blood vessels in the brain. It is an important structure that protects the brain from inflammation in the blood. However, several studies have shown that the blood-brain barrier may be leakier in people with AD. Using a brain scan technique we have measured how leaky the blood-brain barrier is in a small study of 15 people with AD and 17 people without dementia. We also measured levels of inflammation in blood and urine samples.
Our results showed that there was no difference in blood-brain barrier leakiness between the group of people with AD and the group without dementia. There was also no link between leakiness of the blood-brain barrier in people with AD and the rate at which their memory declined over one year.
This research has helped us to design a larger study that will be able to measure blood-brain barrier leakiness in 70 people, and to assess them over two years. These research studies will improve our understanding of the factors that cause worsening symptoms for people with AD. They will also help to identify whether our brain scan could predict those people with AD whose symptoms may decline faster.REC name
South Central - Oxford A Research Ethics Committee
REC reference
21/SC/0031
Date of REC Opinion
15 Feb 2021
REC opinion
Favourable Opinion