Controlling the level of a fatty acid in the brain could help treat Alzheimer's disease, a new study has claimed.
Researchers at the Gladstone Institute of Neurological Disease (GIND) and the University of California 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).
"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," Nature quoted Lennart Mucke, M.D., GIND director and senior author of the study, as saying.
The researchers used a large scale profiling approach 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 researchers lowered PLA2 levels in the Alzheimer mice by genetic engineering. They found that 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.
"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," Sanchez-Mejia added.
The study is published in the issue of Nature Neuroscience.