A study found that the blood-brain barrier was leakier in a group of people with Alzheimer's disease than their healthy counterparts. The researchers suggest this means increased brain-barrier permeability may be a key contributor to the early stages of the disease.
The team, including Walter H. Backes, a professor in medical physics at Maastricht University Medical Center in the Netherlands, reports the study in the journal Radiology.
Prof. Backes says:
"Blood-brain barrier leakage means that the brain has lost its protective means, the stability of brain cells is disrupted and the environment in which nerve cells interact becomes ill-conditioned. These mechanisms could eventually lead to dysfunction in the brain."
The blood-brain barrier (BBB) separates the brain from circulating blood to keep brain tissue healthy. It is a collection of specialized cells and cellular components that line the walls of blood vessels in the brain and the rest of the central nervous system.
The BBB controls the delivery of important nutrients, blocks substances that can harm the brain, and removes waste from the brain.
Alzheimer's disease is the most common form of dementia, an illness that disrupts memory, thinking and behavior. Symptoms usually come on slowly and worsen over time, eventually preventing people from living independently. The disease accounts for 60-80 percent of dementia cases.
Potential key mechanism in early Alzheimer's
For their study, the team used contrast-enhanced magnetic resonance imaging (MRI) to identify leakages in the BBB of patients with early Alzheimer's.
- There are over 5 million people living with Alzheimer's disease in the United States
- This number is expected to rise to nearly 14 million by 2050
- Alzheimer's disease kills more Americans than breast and prostate cancer combined.
Contrast-enhanced MRI allows researchers to identify more clearly the different fluids in the brain. Prof. Backes says it helps to spot tiny changes in blood vessels - even in cases where no directly visible cerebrovascular abnormalities can be seen.
The team compared the MRI scans of 16 patients with early Alzheimer's disease with those of 17 healthy people of the same age (the controls). They measured BBB leakage rate and made a histogram map that showed how much brain tissue was affected.
The results showed that the BBB leakage rate was higher in the Alzheimer's disease group than the controls.
From the histogram maps, the researchers say they could see that the leakage was distributed throughout the cerebrum - the largest part of the brain.
The Alzheimer's disease group had a significantly higher proportion of gray matter brain tissue affected by BBB leakage than the controls. The affected gray matter included the cortex, the outer layer of the brain.
From other research, scientists know that two features of Alzheimer's disease - the plaques and tangles of faulty protein that clog up the brain - tend to spread through the cortex as the disease progresses.
On closer inspection of the histogram data, the team also found evidence of very subtle BBB impairment in the white matter of the brain.
The researchers also found a link between the extent of BBB impairment and reduction in cognitive performance.
They suggest the findings point to impairments in BBB as a potential key mechanism in the early stages of Alzheimer's disease.
When they added diabetes and other non-cerebral circulation diseases to their analysis, the researchers found they did not affect the results, strengthening the case for a direct link between BBB impairment and Alzheimer's disease.
"For Alzheimer's research, this means that a novel tool has become available to study the contribution of blood-brain barrier impairment in the brain to disease onset and progression in early stages or pre-stages of dementia."
Prof. Walter H Backes