Alzheimer's Linked To Fatty Acids

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Main Category: Alzheimer's / Dementia
Also Included In: Neurology / Neuroscience
Article Date: 20 Oct 2008 - 0:00 PDT

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US scientists working with laboratory mice have discovered that complete or partial removal of an enzyme that regulates fatty acid levels lessened the memory and learning deficits of Alzheimer's and could one day lead to a new treatment for the neurodegenerative disease in humans.

The research was conducted by scientists at the Gladstone Institute of Neurological Disease (GIND) in San Francisco, California, the University of California San Francisco (UCSF), and other research centres in the US, and was published in the 19 October advanced online issue of Nature Neuroscience.

The researchers said they found specific fatty acids that may contribute to Alzheimer's and this could open a door to a new kind of treatment.

Alzheimer's is a brain disease that leads to progressive loss of cognitive abilities like memory, thinking and learning. In the US there are over 5 million people living with the condition, and while there are treatments to ease the symptoms they are not very effective and there is no cure.

GIND director and senior author of the study, Dr Lennart Mucke said:

"Several different proteins have been implicated in Alzheimer's disease, but we wanted to know more about the potential involvement of lipids and fatty acids."

The brain takes up fatty acids and incorporates them into phospholipids, a type of fat that makes up the membrane that surrounds cells and protects them from the external environment.

Using large scale profiling of fatty acids, an approach known as "lipidomics", Mucke and colleagues compared the fatty acids in the brains of normal mice with mice genetically bred to have a condition with physiological and memory symptoms similar to Alzheimer's in humans.

Lead author Dr Rene Sanchez-Mejia said:

"The most striking change we discovered in the Alzheimer mice was an increase in arachidonic acid and related metabolites in the hippocampus, a memory center that is affected early and severely by Alzheimer's disease."

Scientists already knew that an enzyme called group IVA phospholipase A2 (or PLA2) released arachidonic acid from phospholipids in the brain, so Mucke and colleagues lowered the levels of PLA2 in the Alzheimer mice by genetic engineering to see what happened.

They found that either removal or even partial reduction of PLA2 prevented memory and learning deficits and other behavioural abnormalities in the Alzheimer mice.

Sanchez-Mejia suggested a possible explanation:

"Arachidonic acid likely wreaks havoc in the Alzheimer mice by causing too much excitation, which makes neurons sick. By lowering arachidonic acid levels, we are allowing neurons to function normally."

Sanchez-Mejia said that a lot more work was needed before a treatment based on regulating fatty acid levels, for example by diet or drugs, could be proven in humans, and the study's main contribution was it showed that "inhibition of PLA2 activity might help prevent neurological impairments in Alzheimer's disease".

Rebecca Wood, Chief Executive of the Alzheimer's Research Trust in the UK, where there are 700,000 people living with Alzheimer's, said the study gave:

"Cause for cautious optimism, as fatty acid levels can be controlled to some extent by diet and drugs."

"However, it is not yet clear if these findings are applicable to humans, and a lot more research is needed before any human trials can be conducted. The Alzheimer's Research Trust is funding several projects in this area," added Wood.

"Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease."
Rene O Sanchez-Mejia, John W Newman, Sandy Toh, Gui-Qiu Yu, Yungui Zhou, Brian Halabisky, Moustapha Cissé, Kimberly Scearce-Levie, Irene H Cheng, Li Gan, Jorge J Palop, Joseph V Bonventre & Lennart Mucke.
Nature Neuroscience, Published online: 19 October 2008.
doi:10.1038/nn.2213

Click here for Abstract.

Source: Journal Abstract, Gladstone Institutes, Alzheimer's Research Trust.

Written by: Catharine Paddock, PhD.


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