Behind the Headlines

Tuesday February 17 2009

The study was in rats without conditions similar to Alzheimer's

“Alzheimer’s could be tackled by treating a sufferer’s liver,” the Daily Mail said. The newspaper reported that researchers have found a link between levels of a toxic protein in the blood and Alzheimer’s disease. It said a study in rats suggests that helping the liver to clear the protein amyloid beta from the blood could fight the disease.

This is preliminary research and does not have any immediate, direct implications for patients with Alzheimer’s disease. The rats did not have conditions that are similar to Alzheimer’s disease, but underwent surgical procedures before being injected with amyloid beta to affect levels of the protein in the body. These conditions do not reflect what would be seen in a human with Alzheimer’s.

More research using animal models of Alzheimer’s disease would be needed to determine whether it is possible to accelerate amyloid beta breakdown in the liver. Whether this has any effect on brain clearance of amyloid beta, or the progression of the disease, will also need to be investigated.

Where did the story come from?

Dr Marcos A Marques and colleagues from the University of Washington and other universities and research centres in the US and Hong Kong carried out the research. The study was funded by the Veterans Affairs Office of Research and Development Medical Research Service, and the National Institutes of Health. The study was published in the peer-reviewed Journal of Alzheimer’s Disease.

What kind of scientific study was this?

Amyloid beta is a short fragment of protein (called a peptide) that builds up in abnormal clumps called plaques in the brain cells of people with Alzheimer’s disease. It is normally broken down in the brain and in the liver after being transported from the brain in the bloodstream.

One theory is that levels of amyloid beta in the blood can affect how fast it is cleared from the brain and central nervous system. The aim of this study in rats was to look at whether this theory was correct.

The researchers randomly assigned eight rats to two groups. One group was given surgery to stop blood flow to the rats’ livers, while the other group had ‘sham surgery’, which did not affect blood flow in this way. The researchers reasoned that, by blocking blood flow to the liver, they could be sure that any amyloid being broken down in the rats was being broken down in their brains.

The anaesthetised rats were injected in the jugular vein with radioactively labelled amyloid beta. Blood samples were collected over time and the radioactivity in these samples was measured to determine the levels of radioactive amyloid beta still circulating in the rats’ bodies.

A second set of experiments used 10 rats that had undergone surgery to stop blood flow to the liver. The researchers injected non-radioactive amyloid beta into the bloodstreams of half of the rats. The left lobe of the rats’ brains was then injected with radioactively labelled amyloid beta along with another radioactive molecule to act as a control to identify non-specific movement of the molecules.

After 70 minutes the other lobe of the rats’ brains was injected with radioactively labelled amyloid beta, and the level of radioactivity in each lobe was measured immediately. These measurements were used to calculate how much of the amyloid beta had been broken down in the brain over the 70-minute period.

What were the results of the study?

The researchers found that after an injection of amyloid beta peptide, the rats whose blood flow to the liver was stopped had a much slower rate of decreasing levels of the peptide in the blood than the rats whose liver blood flow was still intact. This showed that the surgical procedure would allow the level of amyloid beta in the blood to remain high over a period of time, rather than being quickly removed by the liver.

They also found that rats that did not have amyloid beta injected into their bloodstream broke down 41% more of the radioactively labelled amyloid beta in their brains than those injected with high levels of amyloid beta into their bloodstream.

What interpretations did the researchers draw from these results?

The researchers say that their findings support the theory that levels of amyloid beta in the blood can regulate clearance of amyloid beta from the brain.

What does the NHS Knowledge Service make of this study?

This is very preliminary research and does not, at this time, have any direct implications for patients with Alzheimer’s disease. The rats in this study did not have Alzheimer’s-like conditions involving a build-up of amyloid beta in the brain, but were injected with amyloid beta directly into the brain and bloodstream. The rats also had high levels of amyloid beta in their blood because of surgery to stop blood flow to their livers. These conditions do not reflect what would be seen in a human with Alzheimer’s.

More research using animal models of Alzheimer’s disease would be needed to determine whether it is possible to accelerate amyloid beta breakdown in the liver. Whether this has any effect on brain clearance of amyloid beta, or the progression of the disease, will also need to be investigated.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Treating the liver could stave off Alzheimer's, scientists believe. Daily Mail, February 16 2009

Alzheimer's disease could be tackled by treating patients' livers. The Daily Telegraph, February 16 2009

Links to the science

Marques MA, Kulstad JJ, Savard CE et al. Peripheral Amyloid-β Levels Regulate Amyloid-β Clearance from the Central Nervous System. Journal of Alzheimer's Disease 2009; 16: 1387-2877

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