Blood flow in Alzheimer's disease

Jul 27, 2009
Blood flow in Alzheimer's disease

Researchers have discovered that the enzyme, endothelin converting enzyme-2 (ECE-2), may cause the decrease in blood flow in the brain seen in Alzheimer's disease and contribute to progression of the disease.

The study by Jennifer Palmer, BRACE/Reverend Williams PhD Scholar and colleagues at the University of Bristol's Dementia Research Group is published in the current issue [July 2009] of the .

is the most common form of dementia, affecting over half a million people in the UK - a figure expected to double in the next 20 years. Aβ peptide, which accumulates in the brain of Alzheimer's disease patients, is thought to lead to narrowing of the blood vessels and reduction of blood flood in the brain. ECE-2 may contribute to the disease by converting an inactive precursor to endothelin-1, which constricts blood vessels and further reduces blood flow.

Jennifer Palmer said: "Our findings raise the possibility that drugs that can block the actions of endothelin-1 and which are already licensed for treating other diseases may also be of benefit for the treatment of Alzheimer's disease."

Much of the funding for Jennifer Palmer's work comes from Bristol-based charity BRACE. The charity's Chief Executive, Mark Poarch added: "This is real progress and opens up new areas for research. It is also good news for the thousands of local people who have raised money to try to beat Alzheimer's. BRACE is stepping up its fundraising to help scientists press on and find a cure."

The researchers had been studying ECE-2 in human brain tissue that was donated to the South West Dementia Brain Bank at the University of Bristol because the enzyme is also able to break down Aβ peptide, which accumulates in Alzheimer's disease. They found that ECE-2 was markedly elevated in Alzheimer's disease. ECE-2 was particularly abundant in in a part of the brain that is critical for memory and is severely affected by Alzheimer's disease.

The increase in ECE-2 in Alzheimer's disease is not simply a by-product of nerve cell damage. When the researchers looked at brain tissue from patients with a different type of dementia (vascular dementia), ECE-2 levels were normal - no different from the levels in from elderly people without dementia. Further studies showed that the increase seen in Alzheimer's disease of ECE-2 could not be explained by differences in age, gender or time to brain removal after death between the various groups of patients that were studied.

To investigate why ECE-2 might be specifically elevated in Alzheimer's disease, the researchers then examined nerve cells that were grown in a laboratory. They showed that addition of Aβ caused these nerve cells to increase their production of ECE-2. The findings indicate that nerve cells produce more ECE-2 when they are exposed to Aβ.

In the normal brain, blood flow responds to nerve cell activity. If nerve cell activity in a particular part of the brain increases, so does the supply of blood that is needed to meet the extra demand for nutrients such as glucose and oxygen. If this demand is not met, as can happen in Alzheimer's disease, the nerve cells may not function normally and may even sicken and die.

Although the elevated ECE-2 in Alzheimer's disease may help to break down amyloid beta, it may also cause the decrease in blood flow in the , through the production of too much endothelin-1. This may have important implications for treatment. Drugs are available that can block the actions of endothelin-1 and which have been shown to treat some other diseases in which excess endothelin-1 reduces . The findings raise the possibility that these drugs may also be of benefit for the treatment of Alzheimer's disease.

Source: University of Bristol (news : web)

Explore further: Mice study shows efficacy of new gene therapy approach for toxin exposures

add to favorites email to friend print save as pdf

Related Stories

Investigating the causes of Alzheimer's

Nov 22, 2007

Scientists at the University of Bristol are investigating what causes the leaks that develop in blood vessels in Alzheimer's disease, thanks to funding from the UK's leading dementia research charity, the Alzheimer's Research ...

Anti-inflammatory drug blocks brain plaques

Jun 24, 2008

Brain destruction in Alzheimer's disease is caused by the build-up of a protein called amyloid beta in the brain, which triggers damaging inflammation and the destruction of nerve cells. Scientists had previously shown that ...

Epilepsy drug shows potential for Alzheimer's treatment

Dec 08, 2008

A drug commonly used to treat epilepsy could help clear the plaques in the brain associated with Alzheimer's disease, according to researchers at the University of Leeds. The plaques are known to lead to the progressive ...

QBI neuroscientists make Alzheimer's disease advance

Jun 10, 2008

Queensland Brain Institute (QBI) neuroscientists at UQ have discovered a new way to reduce neuronal loss in the brain of a person with Alzheimer's disease. Memory loss in people with Alzheimer's disease can be attributed ...

Recommended for you

How Alzheimer's peptides shut down cellular powerhouses

11 hours ago

The failing in the work of nerve cells: An international team of researchers led by Prof. Dr. Chris Meisinger from the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered ...

User comments : 0