Scientists identify role of fatty acids in Alzheimer's disease

October 19, 2008

Scientists at the Gladstone Institute of Neurological Disease (GIND) and the University of California have found that complete or partial removal of an enzyme that regulates fatty acid levels improves cognitive deficits in a mouse model of Alzheimer's disease (AD). Their findings, which will be published in today's issue of Nature Neuroscience, identified specific fatty acids that may contribute to the disease as well as a novel therapeutic strategy.

AD causes a progressive loss of cognitive functions and results in death. Over 5 million Americans are living with this condition. Although there are treatments to ease the symptoms, these treatments are not very effective and researchers have yet to discover a cure.

"Several different proteins have been implicated in Alzheimer's disease," said Lennart Mucke, M.D., GIND director and senior author of the study, "but we wanted to know more about the potential involvement of lipids and fatty acids."

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. The scientists used a large scale profiling approach ("lipidomics") to compare many different fatty acids in the brains of normal mice with those in a mouse model of Alzheimer's disease that develops memory deficits and many pathological alterations seen in the human condition.

"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," said Rene Sanchez-Mejia, M.D., lead author of the study.

In the brain arachidonic acid is released from phospholipids by an enzyme called group IVA phospholipase A2 (or PLA2). The scientists lowered PLA2 levels in the Alzheimer mice by genetic engineering. Removal or even partial reduction of PLA2 prevented memory deficits and other behavioral abnormalities in the Alzheimer mice.

"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," said Dr. Sanchez-Mejia.

Dr. Mucke added, "in general, fatty acid levels can be regulated by diet or drugs. Our results have important therapeutic implications because they suggest that inhibition of PLA2 activity might help prevent neurological impairments in Alzheimer's disease. But a lot more work needs to be done before this novel therapeutic strategy can be tested in humans."

Source: Gladstone Institutes

Explore further: How a molecular motor untangles protein

Related Stories

How a molecular motor untangles protein

October 1, 2015

A marvelous molecular motor that untangles protein in bacteria may sound interesting, yet perhaps not so important. Until you consider the hallmarks of several neurodegenerative diseases—Huntington's disease has tangled ...

New protein manufacturing process unveiled

September 10, 2015

Researchers from Northwestern University and Yale University have developed a user-friendly technology to help scientists understand how proteins work and fix them when they are broken. Such knowledge could pave the way for ...

Blood test identifies women at risk from Alzheimer's

November 6, 2009

Middle-aged women with high levels of a specific amino acid in their blood are twice as likely to suffer from Alzheimer's many years later, reveals a thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden. ...

Fatty acids clue for Alzheimer's

November 13, 2009

( -- The amount of fatty acids in the brain varies between healthy people and those with Alzheimer's according to new research from the University of Bristol, UK, supported by the Alzheimer's Research Trust.

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.