Lowered PLA2 levels improved memory and other abnormalities in mice, says Nature Neuroscience paper.

Scientists have discovered that complete or partial removal of an enzyme that regulates fatty acid levels improves cognitive deficits in a mouse model of Alzheimer’s disease.

“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,” reports 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 (PLA2).  A genetically engineered decrease or elimination of PLA2 in mice prevented memory deficits and other behavioral abnormalities, according to the researchers.

“Arachidonic acid likely wreaks havoc in the Alzheimer mice by causing too much excitation, which makes neurons sick,” explains Dr. Sanchez-Mejia. “By lowering arachidonic acid levels, we are allowing neurons to function normally.”

“Several different proteins have been implicated in Alzheimer’s disease,” notes 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.” They thus used a lipodomics to compare different fatty acids in the brains of normal mice with those in a mouse model of Alzheimer’s.

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 researchers, who come from the Gladstone Institute of Neurological Disease and the University of California, admit a lot more work needs to be done before this therapeutic strategy can be tested in humans. The study was published October 19 in Nature Neuroscience.

Previous articleFDA Postpones Review of Two Drugs and Sends Amag Response Letter
Next articleSartorius Adds Bayer’s Product to Portfolio for Virus Inactivation