Fatty acids may be the culprit in Alzheimer's

Oct 21 2008

According to new research from the U.S. controlling the level of a fatty acid in the brain could help treat Alzheimer's disease (AD).

Scientists at the Gladstone Institute of Neurological Disease at the University of California, San Francisco, who were researching the brain changes that lead to Alzheimer's, suggest that reducing excess levels of the acid could influence memory problems and behavioural changes.

In research using mice the researchers examined the fatty acids in the brains of normal mice and compared them with those in mice genetically engineered to have an Alzheimer's-like condition and they identified raised levels of the fatty acid arachidonic acid in the brains of the Alzheimer's mice - the release of arachidonic acid is controlled by the PLA2 enzyme.

Fatty acids are rapidly taken up by the brain and incorporated into phospholipids, a class of fats that form the membrane or barrier that shields the content of cells from the external environment, by an enzyme called group IVA phospholipase A2 (or PLA2).

The scientists found that the removal or even partial reduction of PLA2 prevented memory deficits and other behavioral abnormalities in the Alzheimer mice and they believe fatty acid levels could be controlled through diet or drugs.

AD causes a progressive loss of cognitive functions resulting in death and millions worldwide are struggling to live with the condition; although there are treatments to ease the symptoms, these treatments are not very effective and researchers have yet to discover a cure.

Dr. Rene Sanchez-Mejia says the most striking change discovered in the Alzheimer's mice was an increase in arachidonic acid and related metabolites in the hippocampus - the hippocampus is a memory centre that is affected early and severely by Alzheimer's disease and the arachidonic acid appeared to wreak havoc in the Alzheimer mice by causing too much excitation, which makes neurons sick.

Dr. Sanchez-Mejia also suggests that too much arachidonic acid might over-stimulate brain cells, and that lowering levels allowed them to function normally.

Dr. Lennart Mucke, who led the research says fatty acid levels can usually be regulated by diet or drugs and he believes the results have important therapeutic implications because they suggest that inhibition of PLA2 activity might help prevent neurological impairments in Alzheimer's disease, but he says more research is needed before the novel therapeutic strategy can be tested on humans.

Experts say the research is "robust and exciting" and is cause for cautious optimism, as fatty acid levels can be controlled to some extent by diet and drugs.

The research is published in Nature Neuroscience.