“A fatty acid, an ingredient found in foods considered healthy, could harm brain cells and raise the risk of getting Alzheimer's disease” The Guardian reported. It said a study has found that high levels of arachidonic acid, an Omega 6 fatty acid, are linked to brain changes commonly found in people with Alzheimer's.
The reports are based on a study in mice which investigated the metabolism of fats in the brain. It used an “Alzheimer’s model” that was designed to mimic the disease in humans. To have a better idea of how accurate the model is, more studies will need to be carried out first in human tissues and then in living humans. These will need to establish whether levels of arachidonic acid are higher in the brains of Alzheimer’s patients, and whether reducing these levels and the levels of associated chemicals leads to improvements. There is other evidence suggesting that some fatty acids (Omega 3) might have a protective role for dementia.
Where did the story come from?
Dr Rene O Sanchez-Mejia and colleagues from the Gladstone Institute of Neurological Disease in San Francisco, other medical and academic institutes in California, and from Harvard Medical School carried out this study. The research was funded by the National Institutes of Health, the US Department of Agriculture Agricultural Research Service. The study was published in the peer-reviewed medical journal, Nature.
What kind of scientific study was this?
In this laboratory study in mice, the researchers wanted to further explore the role of fatty acids in Alzheimer’s disease. To do this, they used a mouse model, involving a type of mouse that has been bred to have symptoms similar to Alzheimer’s. In these mice, the mechanism that manufactures a protein called human amyloid precursor protein (hAPP) is faulty. This gives the mice age-dependent problems with learning and memory, and they have altered behaviour and premature mortality. The researchers proposed that fatty acids play a part in these reactions, and carried out a series of experiments on the mutant mice to profile the fatty acids involved. They were particularly interested in reactions involving the enzyme phospholipase (PLA2), known to be involved in releasing fatty acids in the brain from phospholipids.
The researchers measured the amount of several components of fatty acid metabolism in the hippocampal regions of the brains of the mutant mice, and compared them with the levels in the brains of normal, non-mutant mice. They also explored the effects of inhibiting the activity of a form of the enzyme phospholipase (GIVA- PLA2) which they had previously found to be higher in the brains of mutant mice with an Alzheimer’s like disease.
A series of experiments in live mice was also carried out, including cross-breeding hAPP mice with mice that could not make GIVA- PLA2. In these mice, the researchers measured the levels of arachidonic acid in their brains and gave them a memory test called the Morris water maze.
The researchers also compared levels of GIVA- PLA2 in samples from the brains of people who had died with Alzheimer’s with samples from the brains of non-demented controls.
What were the results of the study?
The researchers found that the mutant hAPP mice had higher levels of arachidonic acid (an Omega 6 fatty acid) and some types of prostaglandins (a product of the metabolism of fatty acids) in the hippocampus than the normal mice. They say that these differences were not apparent in the cortex region of the brain and may contribute to cell toxicity.
There were also increased levels of other chemicals involved in this fatty acid metabolic pathway, including a particular enzyme (a form of PLA2 called GIVE-PLA2) that is associated with reactions involving arachidonic acid. Inhibiting the activity of this enzyme appeared to protect hAPP mice from the harmful effects of their mutations (i.e. did not lead to increased levels of free arachidonic acid). These mice also performed better on some aspects of the memory test than hAPP mice that had fully functioning GIVA-PLA2. Inhibition of GIVA-PLA2 also reduced hyperactivity of hAPP mice and improved their survival.
When the researchers looked at human cells, they found that levels of GIVA- PLA2 were elevated in the hippocampus region of people with Alzheimer’s compared to controls.
What interpretations did the researchers draw from these results?
The researchers concluded that GIVA-PLA2 may contribute to the development of brain abnormalities associated with Alzheimer’s disease. This discovery may mean that these chemical pathways are a useful target for therapies for this disease.
What does the NHS Knowledge Service make of this study?
This study in mice has shed light on complex reactions in the brain that may be involved in the symptoms of Alzheimer’s disease. In particular, these relate to the metabolism of the Omega 6 fatty acid, arachidonic acid, which was found to be at elevated levels in the brains of mutant mice.
The study used an “Alzheimer’s model” in mice with a particular mutation, meaning they have faulty production of amyloid precursor protein (APP). While the role of APP is not absolutely clear, it is involved in regulation of synapse function and brain plasticity (rewiring).
The news coverage of this study might lead some people to believe that it proves that Omega 6 increases the risk of Alzheimer’s. However, this is not the case for a number of reasons:
- The majority of these experiments were conducted in small groups of mice.
- The study did not measure actual levels of arachidonic acid in human cells, even in the part that involved human tissue.
- This was a study of how fatty acids are metabolised in the brain and did not involve mice or humans being fed fatty acids in their diet.
Two important questions need to be answered before the relevance of these findings in treating Alzheimer’s in humans is known. Firstly, whether the ‘Alzheimer’s model’ used here is an accurate model of dementia in humans and, secondly, whether humans with dementia also have high levels of arachidonic acid. But what is clear is that this is very preliminary research and any dementia treatments based on the results of this study are a long way off.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 20 October 2008
BBC News, 20 October 2008
The Guardian, 20 October 2008
Daily Mail, 20 October 2008
Links to the science
Nature Neuroscience 2008; Published online: 19 October