Fatty acids play truant in Alzhemier’s disease


Washington : Complete or partial removal of an enzyme that regulates fatty acid levels improves brain related deficits in a mouse model of Alzheimer’s disease, according to new research.

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Scientists from Gladstone Institute of Neurological Disease (GIND) and University of California have identified specific fatty acids that may contribute to the disease as well as a novel therapeutic strategy.

Alzheimer’s disease (AD), which afflicts over five million Americans, causes a progressive loss of brain related functions and eventual death. Although existing treatments might ease symptoms, they are not very effective and researchers are yet to discover a cure.

“Several different proteins have been implicated in Alzheimer’s disease,” said Lennart Mucke, GIND director and co-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 AD that develops memory failure and many pathological alterations, according to a GIND release. Their findings were published in the latest issue of Nature Neuroscience.

“The most striking change we discovered in the Alzheimer mice was an increase in arachidonic acid and related metabolites in the hippocampus, a memory centre that is affected early and severely by Alzheimer’s disease,” said Rene Sanchez-Mejia, another co-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 Sanchez-Mejia.